Leiv Otto Watne

• Frich, Wilhelm; Verlo, Kristine Ringnes; Borda, Miguel Germán; Jackson, Thomas Andrew; Livingston, Gill & Myrstad, Christian [Vis alle 15 forfattere av denne artikkelen] (2026). Population-based incidence rate of in-hospital delirium in older adults in Norway—a HUNT study. Age and Ageing. ISSN 0002-0729. 55(10). doi: 10.1093/ageing/afag297. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Most studies of delirium occurrence are based on selected hospitalised populations or administrative data. We aimed to estimate the incidence rate of in-hospital delirium in older adults and to assess use of the International Classification of Diseases, 10th Revision (ICD-10) delirium code (F05) in electronic health records. Methods This population-based cohort study included 9956 participants aged ≥70 years from HUNT4 70+. Participants were followed from the date of study participation (2017–19) until 31 December 2023. In-hospital delirium was identified by retrospective chart review of all admissions during follow-up, using Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria. Incidence rates were estimated using the first delirium episode per participant, weighted for non-participation. Results During follow-up, 1507 participants (15.1%) experienced ≥1 in-hospital delirium episode. The weighted incidence rate was 33.1 (95% CI 31.5–34.9) per 1000 person-years and increased with age from 11.4 (age 70–74) to 109.0 (age ≥90) per 1000 person-years. Men had higher incidence rates than women across age groups. Among admissions with delirium, 11.9% had an ICD-10 discharge delirium diagnosis code (F05). Conclusion In-hospital delirium was common, increased markedly with age and was rarely captured by diagnostic coding. Low coding rates suggest that routine health-care data substantially underestimate delirium burden. Under-recognition of delirium may limit opportunities for follow-up in a group at high risk of adverse outcomes. With an ageing population, the burden of delirium is likely to increase for individuals and health-care systems. Our findings support systematic approaches to improve identification and management.

• Titlestad, Irit; Watne, Leiv Otto; Blennow, Kaj; Zetterberg, Henrik; Myrstad, Marius & Dunjic, Emilija [Vis alle 15 forfattere av denne artikkelen] (2026). CSF neurofilament light chain concentration in patients with delirium following hip fracture: a multicenter prospective study. BMC Geriatrics. 26(1). doi: 10.1186/s12877-026-07630-4. Fulltekst i vitenarkiv Vis sammendrag

  Background Studies suggest delirium is associated with neuronal injury, which may further raise mortality risk. Neuronal injury can be assessed by measuring neurofilament light chain (NFL) concentrations in cerebrospinal fluid (CSF). This study aimed to investigate the association of CSF-NfL with delirium and mortality in patients with hip fracture. Methods The study comprised two prospective cohorts of 548 hip fracture patients with per-operative CSF samples. CSF-NfL concentrations were measured using a commercial ELISA. Delirium was assessed daily from admission until the fifth postoperative day and survival censored at one year. The multivariable analyses (Logistic and Cox regression) were adjusted for age, sex, glomerular filtration rate, dementia status, comorbidity, and Activities of Daily Living. Additionally, Cox regression was adjusted for delirium. Results In total, 259 (52%) patients developed delirium. In univariate analysis, CSF-NfL was higher among patients with delirium (2116 pg/ml versus 1366 pg/ml, odds ratio (OR) 2.21, (95% confidence interval (CI) [1.75,2,78], P < 0.001). In adjusted analysis, CSF-NfL was not significant (OR 1.29, [0.92,1.81], P = 0.128) and only remained significantly associated with delirium in the subgroup of patients without dementia (OR 1.84, [1.17, 2.89], P = 0.007). In unadjusted analysis of mortality, CSF-NfL was significantly associated with death at one year (hazard ratio (HR) 1.60, [1.37, 1.87], P < 0.001) but not in adjusted analysis (HR 1.03 [0.84, 1.26], P = 0.736). Conclusions Our findings show that CSF-NfL concentrations were associated with delirium in patients without pre-existing dementia, suggesting possible undiagnosed dementia or, less likely, delirium-related neuronal injury. The CSF-NfL-associated mortality hazard was non-significant after adjustment, mainly for delirium. Thus, the clinical context must be considered when studying CSF-NfL and delirium.

• Grødem, Edvard Olaf Sætersdal; Pineiro, Didac Vidal; Sørensen, Øystein; Bartrés-Faz, David; Brandmaier, Andreas M. & Cattaneo, Gabriele [Vis alle 20 forfattere av denne artikkelen] (2026). Stable individual differences dominate adult brain volume variation until later life. Imaging Neuroscience. 4. doi: 10.1162/IMAG.a.1242. Fulltekst i vitenarkiv
• Pan, Junping; Wang, Ping-Jie; Zhang, Jianying; Knapskog, Anne-Brita; Watne, Leiv Otto & Wang, He-Ling [Vis alle 40 forfattere av denne artikkelen] (2026). Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer’s disease pathology. Nature Aging. 6(5), s. 1079–1102. doi: 10.1038/s43587-026-01108-z. Fulltekst i vitenarkiv
• Saiyed, Nazia; Pandya, Vaibhav; Pan, Xiaobei; Cuperlovic-Culf, Miroslava; Ashrafi, Nadia & Kant, Shiva [Vis alle 15 forfattere av denne artikkelen] (2026). Unraveling the role of polyamine metabolism in postoperative delirium: insights into biochemical mechanisms and biomarker potential. npj Aging. 12. doi: 10.1038/s41514-025-00324-y. Fulltekst i vitenarkiv Vis sammendrag

  Postoperative delirium (POD) is a common complication in older surgical patients, linked to long-term cognitive decline and progression to dementia, yet its mechanisms remain unclear. We investigated arginine-related metabolites (ARMs) in cerebrospinal fluid (CSF) from 248 patients undergoing elective-surgery: 25 developed POD. Targeted mass spectrometry, gene expression profiling, and machine learning were applied to identify metabolic predictors. POD patients showed significant correlations with citrulline, ornithine, and glutamine, while models highlighted glutamine, glutamic acid, putrescine, N1-acetylspermidine, and spermidine as key biomarkers, achieving >77% predictive accuracy. Cluster and pathway analyses revealed POD-specific shifts in GABA synthesis and polyamine metabolism, contrasting with urea cycle dominance in non-POD cases. Associations persisted after adjusting for age and CSF Aβ42. Preoperative profiles in polyamine metabolism, ammonia detoxification, and neurotransmitter regulation suggest underlying neuroinflammatory and oxidative stress vulnerabilities that reduce resilience. Targeting polyamine biosynthesis may offer novel preventative and therapeutic strategies to mitigate POD and dementia risk.

• Trzpis, Monika; Melvær, Giil Lasse; Hov, Johannes Espolin Roksund; Pollmann, Christian Thomas; Idland, Ane-Victoria & Myrstad, Marius [Vis alle 12 forfattere av denne artikkelen] (2026). Assessment of the bacteria-derived metabolite TMAO as a potential factor contributing to the pathophysiology of delirium in elderly patients with hip fracture. Brain, Behavior, and Immunity. ISSN 0889-1591. 136. doi: 10.1016/j.bbi.2026.106590. Fulltekst i vitenarkiv Vis sammendrag

  Background: Trimethylamine N-oxide (TMAO) concentrations are dependent on several factors including gut microbial metabolism of dietary nutrients. High TMAO levels have been implicated in the pathogenesis of age-related cognitive impairment. We hypothesized that TMAO may contribute to the pathophysiology of delirium. Methods: In this observational study, we analyzed TMAO concentration in blood and cerebrospinal fluid (CSF) samples from 487 hip fracture patients. Delirium status was set according to the DSM-5 criteria, and pre-existing cognitive impairment by the IQCODE. We performed a logistic regression analysis to examine the association between TMAO and delirium, adjusting for age, pre-existing dementia, and renal function. Results: The median TMAO concentration was significantly higher in patients with delirium (3.9 µM, IQR 2.6–6.6 in blood; 2.5 µM, IQR 1.3–4.9 in CSF) than without delirium (3.0 µM, IQR 2.1–5.1 in blood; P = 0.02, and 1.6 µM, IQR 0.9–3.0 in CSF, P < 0.001). After adjusting for confounders, the association between TMAO and delirium remained significant in CSF (OR = 1.5, 95%CI 1.09–2.05, P = 0.01). Analysis stratified by dementia showed the association was significant only for CSF TMAO among patients without pre-existing dementia (OR = 1.6, 95% CI 1.09–2.30, P = 0.02). Conclusions: The increased concentration of TMAO in CSF is positively associated with delirium among patients without pre-existing dementia. Our finding supports previous observations that the gut derived metabolites may be relevant in delirium, but the pathophysiology may differ in patients with and without pre-existing dementia.

• Henjum, Kristi; Neerland, Bjørn Erik; Blennow, Kaj; Zetterberg, Henrik; Pollmann, Christian Thomas & Olsen, Roy Bjørkholt [Vis alle 13 forfattere av denne artikkelen] (2026). Biomarkers of Alzheimer's disease pathophysiology and delirium. EBioMedicine. 127. doi: 10.1016/j.ebiom.2026.106252. Fulltekst i vitenarkiv
• Berntsen, Thea; Blennow, Kaj; Zetterberg, Henrik; Brekke, Ingrid Fæhn; Hella, Mathias Nikolai Petersen & Lian, Tom [Vis alle 16 forfattere av denne artikkelen] (2026). Increased cerebrospinal fluid YKL-40 concentration in hip fracture patients with delirium. Brain Communications. 8(1). doi: 10.1093/braincomms/fcag005. Fulltekst i vitenarkiv Vis sammendrag

  The underlying mechanisms of the neuropsychiatric syndrome delirium are still unknown, but neuroinflammation is a central hypothesis. Chitinase-3-like-protein-1 (YKL-40/CHI3L1) is considered a marker of neuroinflammation when measured in cerebrospinal fluid (CSF). The aim of this study was to examine concentrations of CSF YKL-40 in patients with and without delirium, to enhance the understanding of delirium pathophysiology. A total of 545 hip fracture patients were included from two similar cohorts. CSF samples were collected in conjunction with spinal anaesthesia for hip fracture surgery. The patients were screened for delirium both pre- and postoperatively. Those with delirium were further divided into subgroups based on whether they developed it before surgery (prevalent delirium) or after surgery (incident delirium). Among patients without delirium, those who met some, but not all diagnostic criteria, were classified as having subsyndromal delirium. Prefracture cognitive function was assessed, and American Society of Anaesthesiologists physical status score was included as a marker of comorbidity. In total, 257 (47%) of the patients developed delirium. These patients were older and had a higher prevalence of dementia and severe systemic diseases. Among the patients without dementia, those with delirium had higher median concentration of CSF YKL-40 compared with those without delirium (first cohort: 175 versus 132 ng/mL, P = 0.01, second cohort: 243 versus 174 ng/mL, P < 0.001). No association was found among the patients with dementia. The results remained consistent when adjusting for age and comorbidity. No difference in median CSF YKL-40 concentration was found between patients who had delirium at the time of surgery (prevalent delirium) and those who developed it afterwards (incident delirium). Our findings support the hypothesis of neuroinflammation as a mechanism for delirium in patients without dementia.

• Akdeniz, Bayram Cevdet; Bahrami, Shahram; Hagen, Espen; Fuhrer, Julian; Fominykh, Vera & Shadrin, Alexey [Vis alle 108 forfattere av denne artikkelen] (2026). Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer’s Disease in European Populations: Development and Validation. medRxiv. doi: 10.1101/2025.07.28.25332293. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Objectives Polygenic hazard score (PHS) models can be used to predict the age-associated risk for complex diseases, including Alzheimer’s disease (AD). In this study, we present an improved PHS model for AD that incorporates a large number of genetic variants and demonstrates enhanced predictive accuracy for age of onset in European populations compared to alternative models. Methods We used the genotyped European Alzheimer & Dementia Biobank (EADB) sample (n=42,120) to develop and evaluate the performance of the PHS model. We developed a PHS model building on 720 genetic variants, including Apolipoprotein E ( APOE ) ε2 and ε4 alleles. We used Elastic Net-regularized Cox regression approach to develop the PHS model. Results The new PHS model (EADB720) improved prediction accuracy compared to alternative models in European populations, with the Odds Ratio OR80/20 from the highest quintile of risk (80th risk percentile and above) to the lowest quintile of risk (20th risk percentile and below) varying between 5.10 and 13.15 within the range of age of onset from 65 – 85 years. Our model also improved risk stratification across ε3/3 individuals of European ancestry (OR80/20 ranges from 1.95 to 3.52). It was also successfully validated in independent datasets (HUSK, DemGene and ADNI) by achieving OR80/20 up to 10.00 in each independent dataset. Conclusion Our EADB720 model significantly improves the accuracy of age-associated risk of AD across European populations (pval<0.03). Accurately predicting the age of onset of AD is of large clinical importance to implementing new AD medication and early intervention in clinical settings.

• Hella, Mathias Nikolai Petersen; Sønnesyn, Hogne; Hetland, Hanne Brit; Vik-Mo, Audun Osland; Djuv, Ane & Sunde, Anita Lenora [Vis alle 10 forfattere av denne artikkelen] (2025). Delirium prevalence and incidence in acutely admitted older patients: an observational cohort study. BMC Geriatrics. 26. doi: 10.1186/s12877-025-06903-8. Fulltekst i vitenarkiv Vis sammendrag

  Background Delirium is common in acutely ill older adults and is associated with multiple unfavourable outcomes, including an increased risk of dementia and death. As the population ages and more people live with dementia, updated and accurate estimates of delirium prevalence are important. The primary aim of this study was to identify delirium point prevalence in the emergency department and incidence during hospitalisation. Our secondary aim was to compare outcomes: length of stay, need for a higher level of care, and mortality after discharge in patients with and without delirium. Methods In this unselected observational cohort study, all older adults aged 65 years or above acutely admitted to the emergency department of a large Norwegian hospital during a 5-day and 4-night midweek period, were screened for delirium by the 4 “A”s test. A final consensus delirium diagnosis was made based on review of all available information in the patients’ electronic health record to consider if The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition’s criteria (DSM-V) for delirium were fulfilled. Results Of 240 patients assessed, 14% (n = 33) fulfilled DSM-V criteria for delirium in the emergency department, and 8% (n = 17) of the remaining 207 patients developed delirium later during the hospitalisation. Only 4 of the 50 patients with delirium (8%) had a documented diagnosis of delirium in their discharge summary. For patients with delirium, the current hospital admission was more often a readmission (42% vs. 18%, p < 0.001). Delirium patients also had longer hospitalisations (4 vs. 2 days, p < 0.001), and higher 9-month mortality (52% vs. 14%, p = 0.002), corrected for age, sex and severity of acute illness by The National Early Warning Score 2. Conclusions Delirium was common and underdiagnosed in our study and associated with unfavourable outcomes for the patients. Delirium prevention, identification and management should be key priorities for the health care system. Trial registration Our article does not report results of a health care intervention, and the protocol is not registered in a trial registry.

• Pineiro, Didac Vidal; Sørensen, Øystein; Strømstad, Marie Lorentsen; Amlien, Inge; Baaré, William & Bartrés-Faz, David [Vis alle 74 forfattere av denne artikkelen] (2025). Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change. Nature Communications. 16(1). doi: 10.1038/s41467-025-66354-y. Fulltekst i vitenarkiv Vis sammendrag

  Brain atrophy is a key factor behind episodic memory loss in aging, but the nature and ubiquity of this relationship remains poorly understood. This study leverages 13 longitudinal datasets, including 3737 cognitively healthy adults (10,343 MRI scans; 13,460 memory assessments), to determine whether brain change-memory change associations are more pronounced with age and genetic risk for Alzheimer’s Disease. Both factors are associated with accelerated brain decline, yet it remains unclear whethermemory loss is exacerbated beyond what atrophy alone would predict. Additionally, we assess whether memory decline aligns with a global pattern of atrophy or stems from distinct regional contributions. Our mega-analysis reveals a nonlinear relationship between memory decline and brain atrophy, primarily affecting individuals with above-average brain structural decline. The associations are stronger in the hippocampus but also spread across diverse cortical and subcortical regions. The associations strengthen with age, reachingmoderate associations in participants in their eighties. While APOE ε4 carriers exhibit steeper brain and memory loss, genetic risk has no effect on the change-change associations. These findings support the presence of common biological macrostructural substrates underlying memory function in older age which are vulnerable to multiple age-related factors, even in the absence of overt pathological changes.

• Fjell, Anders Martin; Røgeberg, Ole Jørgen; Sørensen, Øystein; Amlien, Inge; Bartrés-Faz, David & Brandmaier, Andreas M. [Vis alle 23 forfattere av denne artikkelen] (2025). Reevaluating the role of education on cognitive decline and brain aging in longitudinal cohorts across 33 Western countries. Nature Medicine. ISSN 1078-8956. 31, s. 2967–2976. doi: 10.1038/s41591-025-03828-y. Fulltekst i vitenarkiv Vis sammendrag

  Why education is linked to higher cognitive function in aging is fiercely debated. Leading theories propose that education reduces brain decline in aging and enhances tolerance to brain pathology or that it does not affect cognitive decline but, rather, reflects higher early-life cognitive function. To test these theories, we analyzed 407,356 episodic memory scores from 170,795 participants older than 50 years, alongside 15,157 brain magnetic resonance imaging scans from 6,472 participants across 33 Western countries. More education was associated with better memory, larger intracranial volume and slightly larger volume of memory-sensitive brain regions. However, education did not protect against age-related decline or weakened effects of brain decline on cognition. The most parsimonious explanation for the results is that the associations reflect factors present early in life, including propensity of individuals with certain traits to pursue more education. Although education has numerous benefits, the notion that it provides protection against cognitive or brain decline is not supported. In a large cross-national study, education was linked to better memory and larger brain volumes but not to slower cognitive or brain decline with age, suggesting that the association reflects early-life factors rather than neuroprotective effects in aging.

• Aarskog, Nikolai Ravn; Bjørsrud, Hanna Othilie Lindvig; Holten, Aleksander Rygh; Watne, Leiv Otto; Neerland, Bjørn Erik & Rostrup, Morten (2025). Ventilatory response and delirium risk in hospitalised patients with acute hypoxia due to COVID-19. Scientific Reports. 15. doi: 10.1038/s41598-025-13016-0. Fulltekst i vitenarkiv Vis sammendrag

  Mountaineers with a high ventilatory response to hypoxia experience greater cognitive impairment at high altitude, possibly because hyperventilation causes hypocapnia, cerebral vasoconstriction and ultimately cerebral ischaemia. We hypothesised that a high ventilatory response, and consequently a lower arterial partial pressure of carbon dioxide (PaCO2), could increase the risk of delirium in hospitalised patients with acute hypoxia. To test our hypothesis, we conducted a cohort study in which PaCO2 and arterial oxygen saturation were measured upon hospital admission in 126 patients with COVID-19. After adjusting for oxygen saturation, we found that a lower PaCO2 was associated with a higher risk of delirium during hospital admission (risk ratio 1.67 [95% confidence interval 1.09–2.54] per 1 kilopascal reduction, P = 0.017). The association remained statistically significant after adjusting for other well-established risk factors for delirium. This finding supports our hypothesis that a high hypoxic ventilatory response increases the risk of delirium in patients with acute hypoxia.

• Hella, Mathias Nikolai Petersen; Halaas, Nathalie Bodd; Sønnesyn, Hogne; Bergland, Anne Katrine; Hetland, Hanne Brit & Blennow, Kaj [Vis alle 14 forfattere av denne artikkelen] (2025). Neurogranin in cerebrospinal fluid as a marker of synaptic dysfunction in hip fracture patients with delirium: a multicentre cross-sectional study. BMJ Open. 15(11). doi: 10.1136/bmjopen-2024-097579. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: Neurogranin (Ng) has a role in synaptic plasticity and is considered a biomarker of synaptic dysfunction, a process hypothesised to be important in delirium. Few studies examining Ng in delirium exist, with mixed findings. This study aimed to investigate associations between cerebrospinal fluid (CSF) Ng concentrations and delirium in acutely admitted hip fracture patients. Design: Cross-sectional study. Setting: Acutely admitted orthopaedic patients with hip fracture recruited from four participating hospitals in eastern Norway, representing secondary and tertiary care settings. Participants: This study included 392 hip fracture patients. All admitted hip fracture patients operated in spinal anaesthesia were, regardless of age, considered for inclusion. Methods: An in-house ELISA was used to measure CSF Ng concentration in patients acutely admitted with a hip fracture (n=392). Delirium status was evaluated daily according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Editions criteria independently by two experienced geriatricians. A value > 3.44 on The Informant Questionnaire on Cognitive Decline in the Elderly was used as a surrogate marker of probable dementia. Results: 180 patients (46 %) developed delirium and 70% of these had dementia. CSF Ng concentration did not differ significantly between those with and without delirium (176 pg/mL vs 164 pg/mL), with an estimated difference in medians of 12 (95% CI −5.8 to 29.8), p=0.185. Analyses adjusted for age, gender and dementia status did not show a statistically significant difference in Ng concentrations between the patients. Conclusions: We did not find an association between delirium and CSF concentrations of Ng. This could imply that synaptic dysfunction and degeneration, involving Ng, are not key processes in the development of delirium. Further studies on other synaptic proteins are warranted to better explore synaptic dysfunction’s potential role in the pathophysiology of delirium.

• Ravndal, Anne; Fjell, Anders Martin; Vidal-Piñeiro, Didac; Sørensen, Øystein; Falch, Emilie Sogn & Kropiunig, Julia [Vis alle 21 forfattere av denne artikkelen] (2025). Sex differences in healthy brain aging are unlikely to explain higher Alzheimer’s disease prevalence in women. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 122(42). doi: 10.1073/pnas.2510486122. Fulltekst i vitenarkiv Vis sammendrag

  As Alzheimer’s disease (AD) is diagnosed more frequently in women, understanding the role of sex has become a key priority in AD research. However, despite aging being the primary risk factor for AD, it remains unclear whether men and women differ in the extent of brain decline with age. Using 12,638 longitudinal brain MRIs from 4,726 participants aged 17 to 95 y across 14 cohorts, we examined sex differences in structural brain changes over time, controlling for differences in head size. Men showed greater cortical thickness (CT) decline in the cuneus, lingual, parahippocampal, and pericalcarine regions; surface area decline in the fusiform and postcentral regions; and in older adults, greater subcortical decline in the caudate, nucleus accumbens, putamen, and pallidum. In contrast, women only showed greater surface area decline in the banks of the superior temporal sulcus and greater ventricular expansion in older adults. These results suggest that sex differences in age-related brain decline are unlikely to contribute to the higher AD diagnosis prevalence in women, necessitating research into alternative explanations.

• Vidal-Piñeiro, Didac; Sørensen, Øystein; Strømstad, Marie Lorentsen; Amlien, Inge; Anderson, Micael & Baaré, William F.C. [Vis alle 25 forfattere av denne artikkelen] (2025). Reliability of structural brain change in cognitively healthy adult samples. Imaging Neuroscience. 3, s. 1–25. doi: 10.1162/imag_a_00547. Fulltekst i vitenarkiv Vis sammendrag

  In neuroimaging research, tracking individuals over time is key to understanding the interplay between brain changes and genetic, environmental, or cognitive factors across the lifespan. Yet, the extent to which we can estimate the individual trajectories of brain change over time with precision remains uncertain. In this study, we estimated the reliability of structural brain change in cognitively healthy adults from multiple samples and assessed the influence of follow-up time and number of observations. Estimates of cross-sectional measurement error and brain change variance were obtained using the longitudinal FreeSurfer processing stream. Our findings showed, on average, modest longitudinal reliability with 2 years of follow-up. Increasing the follow-up time was associated with a substantial increase in longitudinal reliability, while the impact of increasing the number of observations was comparatively minor. On average, 2-year follow-up studies require ≈2.7 and ≈4.0 times more individuals than designs with follow-ups of 4 and 6 years to achieve comparable statistical power. Subcortical volume exhibited higher longitudinal reliability than cortical area, thickness, and volume. The reliability estimates were comparable with those estimated from empirical data. The reliability estimates were affected by both the cohort’s age where younger adults had lower reliability of change and the preprocessing pipeline where the FreeSurfer’s longitudinal stream was notably superior than the cross-sectional stream. Suboptimal reliability inflated sample size requirements and compromised the ability to distinguish individual trajectories of brain aging. This study underscores the importance of long-term follow-ups and the need to consider reliability in longitudinal neuroimaging research.

• Zhang, Jianying; Wang, Heling; Lautrup, Sofie Hindkjær; Nilsen, Hilde; Treebak, Jonas T. & Watne, Leiv Otto [Vis alle 28 forfattere av denne artikkelen] (2025). Emerging strategies, applications and challenges of targeting NAD+ in the clinic. Nature Aging. 5(9), s. 1704–1731. doi: 10.1038/s43587-025-00947-6. Fulltekst i vitenarkiv Vis sammendrag

  Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD+ precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD+ research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.

• Bocharova, Mariia; Borza, Tom; Watne, Leiv; Engedal, Knut; O'Brien, John T & Selbæk, Geir [Vis alle 10 forfattere av denne artikkelen] (2025). The role of plasma inflammatory markers in late-life depression and conversion to dementia: a 3-year follow-up study. Molecular Psychiatry. ISSN 1359-4184. 30(7), s. 3029–3038. doi: 10.1038/s41380-025-02908-2. Fulltekst i vitenarkiv
• Ai, Ruixue; Xiao, Xianglu; Deng, Shenglong; Yang, Nan; Xing, Xiaodan & Watne, Leiv [Vis alle 16 forfattere av denne artikkelen] (2025). Artificial intelligence in drug development for delirium and Alzheimer's disease. Acta Pharmaceutica Sinica B (APSB). ISSN 2211-3835. 15(9), s. 4386–4410. doi: 10.1016/j.apsb.2025.04.026. Fulltekst i vitenarkiv
• Dakhil, Shams; Djuv, Ane; Saltvedt, Ingvild Tina; Wyller, Torgeir Bruun; Frihagen, Frede & Johnsen, Lars Gunnar [Vis alle 10 forfattere av denne artikkelen] (2025). Postoperative outcomes in patients operated for extra- and intracapsular hip fractures – a secondary analysis of two randomized controlled trials. BMC Musculoskeletal Disorders. 26. doi: 10.1186/s12891-025-08404-6. Fulltekst i vitenarkiv Vis sammendrag

  Background: Hip fractures are among the most common and serious injuries in older adults. There has been a perception that extracapsular hip fractures have worse outcome than intracapsular hip fractures. We aimed to examine postoperative outcomes in patients operated for extra- and intracapsular hip fractures. Methods: This is a secondary analysis of data from two randomized controlled trials evaluating the effect of orthogeriatric care. Bivariate analyses were conducted, comparing patients with extracapsular fracture to patients with intracapsular fracture. Mortality, length of hospital stay (LOS), new nursing home admissions, operative data and measures of functional and cognitive performance were assessed as endpoints. Results: The primary analysis included 711 patients; 283 patients had an extracapsular fracture and 428 an intracapsular fracture. At four months follow-up, the intracapsular fracture group had significantly better Short Physical Performance Battery (SPPB) (5.0 vs. 4.0, p = 0.007), personal Activities of Daily Living (p-ADL) (17.0 vs. 16.0, p = 0.007) and instrumental ADL (i-ADL) (32.5 vs. 28.0, p = 0.049). There were no statistically significant differences between the groups at 12 months. Conclusions: Patients with an extracapsular fracture had worse mobility and ADL levels four months postoperatively, but there were no clinically relevant differences at 12 months postoperatively.

• Capogna, Elettra; Sørensen, Øystein; Watne, Leiv; Roe, James Michael; Strømstad, Marie Lorentsen & Idland, Ane-Victoria [Vis alle 12 forfattere av denne artikkelen] (2025). Subtypes of brain change in aging and their associations with cognition and Alzheimer’s disease biomarkers. Neurobiology of Aging. ISSN 0197-4580. 147, s. 124–140. doi: 10.1016/j.neurobiolaging.2024.12.009. Fulltekst i vitenarkiv Vis sammendrag

  Structural brain changes underlie cognitive changes and interindividual variability in cognition in older age. By using structural MRI data-driven clustering, we aimed to identify subgroups of cognitively unimpaired older adults based on brain change patterns and assess how changes in cortical thickness, surface area, and subcortical volume relate to cognitive change. We tested (1) which brain structural changes predict cognitive change (2) whether these are associated with core cerebrospinal fluid (CSF) Alzheimer’s disease biomarkers, and (3) the degree of overlap between clusters derived from different structural modalities in 1899 cognitively healthy older adults followed up to 16 years. We identified four groups for each brain feature, based on the degree of a main longitudinal component of decline. The minimal overlap between features suggested that each contributed uniquely and independently to structural brain changes in aging. Cognitive change and baseline cognition were associated with cortical area change, whereas higher baseline levels of phosphorylated tau and amyloid-β related to changes in subcortical volume. These results may contribute to a better understanding of different aging trajectories.

• Knapskog, Anne-Brita; Edwin, Trine Holt; Ueland, Per Magne; Ulvik, Arve; Fang, Fei & Eldholm, Rannveig Sakshaug [Vis alle 11 forfattere av denne artikkelen] (2024). Sex-specific associations of kynurenic acid with neopterin in Alzheimer’s disease. Alzheimer's Research & Therapy. 16(1). doi: 10.1186/s13195-024-01531-7. Fulltekst i vitenarkiv Vis sammendrag

  Background: Sex differences in neuroinflammation could contribute to women’s increased risk of Alzheimer’s disease (AD), providing rationale for exploring sex-specific AD biomarkers. In AD, dysregulation of the kynurenine pathway (KP) contributes to neuroinflammation and there is some evidence of sex differences in KP metabolism. However, the sex-specific associations between KP metabolism and biomarkers of AD and neuroinflammation need to be explored further. Methods: Here we investigate sex differences in cerebrospinal fluid concentrations of seven KP metabolites and sex-specific associations with established AD biomarkers and neopterin, an indicator of neuroinflammation. This study included 311 patients with symptomatic AD and 105 age-matched cognitively unimpaired (CU) controls, followed for up to 5 years. Results: We found sex differences in KP metabolites in the AD group, with higher levels of most metabolites in men, while there were no sex differences in the CU group. In line with this, more KP metabolites were significantly altered in AD men compared to CU men, and there was a trend in the same direction in AD women. Furthermore, we found sex-specific associations between kynurenic acid and the kynurenic acid/quinolinic acid ratio with neopterin, but no sex differences in the associations between KP metabolites and clinical progression. Discussion: In our cohort, sex differences in KP metabolites were restricted to AD patients. Our results suggest that dysregulation of the KP due to increased inflammation could contribute to higher AD risk in women.

• Bellelli, Giuseppe; Triolo, Federico; Ferrara, Maria Cristina; Deiner, Stacie G.; Morandi, Alessandro & Cesari, Matteo [Vis alle 12 forfattere av denne artikkelen] (2024). Delirium and frailty in older adults: Clinical overlap and biological underpinnings. Journal of Internal Medicine. ISSN 0954-6820. 296(5), s. 382–398. doi: 10.1111/joim.20014. Fulltekst i vitenarkiv Vis sammendrag

  Frailty and delirium are two common geriatric syndromes sharing several clinical characteristics, risk factors, and negative outcomes. Understanding their interdependency is crucial to identify shared mechanisms and implement initiatives to reduce the associated burden. This literature review summarizes scientific evidence on the complex interplay between frailty and delirium; clinical, epidemiological, and pathophysiological commonalities; and current knowledge gaps. We conducted a PubMed systematic search in June 2023, which yielded 118 eligible articles out of 991. The synthesis of the results—carried out by content experts—highlights overlapping risk factors, clinical phenotypes, and outcomes and explores the influence of one syndrome on the onset of the other. Common pathophysiological mechanisms identified include inflammation, neurodegeneration, metabolic insufficiency, and vascular burden. The review suggests that frailty is a risk factor for delirium, with some support for delirium associated with accelerated frailty. The proposed unifying framework supports the integration and measurement of both constructs in research and clinical practice, identifying the geroscience approach as a potential avenue to develop strategies for both conditions. In conclusion, we suggest that frailty and delirium might be alternative—sometimes coexisting—manifestations of accelerated biological aging. Clinically, the concepts addressed in this review can help approach older adults with either frailty or delirium from a different perspective. From a research standpoint, longitudinal studies are needed to explore the hypothesis that specific pathways within the biology of aging may underlie the clinical manifestations of frailty and delirium. Such research will pave the way for future understanding of other geriatric syndromes as well.

• Tsui, Alex; Johnstone, Benjamin; Heslegrave, Amanda; Zetterberg, Henrik; Watne, Leiv & Neerland, Bjørn Erik [Vis alle 12 forfattere av denne artikkelen] (2024). Persistent delirium is associated with cerebrospinal fluid markers of neuronal injury. Brain Communications. 6(5). doi: 10.1093/braincomms/fcae319. Fulltekst i vitenarkiv
• Bratseth, Vibeke; Watne, Leiv Otto; Neerland, Bjørn Erik; Halaas, Nathalie Bodd; Pollmann, Christian Thomas & Karabeg, Adi [Vis alle 11 forfattere av denne artikkelen] (2024). Increased cell-free DNA in CSF and serum of hip fracture patients with delirium. Brain Communications. 7(1). doi: 10.1093/braincomms/fcae452. Fulltekst i vitenarkiv Vis sammendrag

  Delirium is a neuropsychiatric syndrome commonly presenting during acute illness. The pathophysiology of delirium is unknown, but neuroinflammation is suggested to play a role. In this cross-sectional study, we aimed to investigate whether cell-free DNA and markers of neutrophil extracellular traps in serum and CSF were associated with delirium and neuronal damage, assessed by neurofilament light chain. Hip fracture patients (n = 491) with a median (25, 75 percentiles) age of 83 (74, 88) years and 69% females were enrolled at Oslo University Hospital, Diakonhjemmet Hospital, Akershus University Hospital and Bærum Hospital. Delirium was assessed daily, pre- and postoperatively. Cognitively healthy adults (n = 32) with a median (25, 75 percentiles) age of 75 (70, 77) years and 53% females were included as controls. Cell-free DNA was measured by using the fluorescent nucleic acid stain Quant-iT PicoGreen® in serum and CSF. Myeloperoxidase-DNA and citrullinated histone H3 were analysed by enzyme-linked immunosorbent assay in serum. Hip fracture patients have significantly higher levels of cell-free DNA and neutrophil extracellular traps in blood than cognitively healthy controls. In hip fracture patients without dementia, cell-free DNA in CSF and serum was significantly higher in patients with (n = 68) versus without (n = 221) delirium after adjusting for age and sex (70 (59, 84) versus 62 (53, 77) ng/ml, P = 0.037) and 601 (504, 684) versus 508 (458, 572) ng/ml, P = 0.007, respectively). In the total hip fracture cohort, CSF levels of cell-free DNA and neurofilament light chain were significantly correlated after adjusting for age and sex (r = 0.441, P < 0.001). The correlation was stronger in those with delirium (r = 0.468, P < 0.001) and strongest in delirious patients without dementia (r = 0.765, P = 0.045). In delirious patients without dementia, significantly higher levels of cell-free DNA in CSF and serum were shown. The association between cell-free DNA and neurofilament light chain suggest simultaneous release of cell-free DNA and neuronal damage during delirium.

• Aksnes, Mari; Schibstad, Mari Haavig; Chaudhry, Farrukh Abbas; Neerland, Bjørn Erik; Caplan, Gideon A. & Saltvedt, Ingvild Tina [Vis alle 17 forfattere av denne artikkelen] (2024). Differences in metalloproteinases and their tissue inhibitors in the cerebrospinal fluid are associated with delirium. Communications Medicine. 4(1). doi: 10.1038/s43856-024-00558-z. Fulltekst i vitenarkiv Vis sammendrag

  Background The aetiology of delirium is not known, but pre-existing cognitive impairment is a predisposing factor. Here we explore the associations between delirium and cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), proteins with important roles in both acute injury and chronic neurodegeneration. Methods Using a 13-plex Discovery Assay®, we quantified CSF levels of 9 MMPs and 4 TIMPs in 280 hip fracture patients (140 with delirium), 107 cognitively unimpaired individuals, and 111 patients with Alzheimer’s disease dementia. The two delirium-free control groups without acute trauma were included to unravel the effects of acute trauma (hip fracture), dementia, and delirium. Results Here we show that delirium is associated with higher levels of MMP-2, MMP-3, MMP-10, TIMP-1, and TIMP-2; a trend suggests lower levels of TIMP-4 are also associated with delirium. Most delirium patients had pre-existing dementia and low TIMP-4 is the only marker associated with delirium in adjusted analyses. MMP-2, MMP-12, and TIMP-1 levels are clearly higher in the hip fracture patients than in both control groups and several other MMP/TIMPs are impacted by acute trauma or dementia status. Conclusions Several CSF MMP/TIMPs are significantly associated with delirium in hip fracture patients, but alterations in most of these MMP/TIMPs could likely be explained by acute trauma and/or pre-fracture dementia. Low levels of TIMP-4 appear to be directly associated with delirium, and the role of this marker in delirium pathophysiology should be further explored.

• Denver, Paul; Tortorelli, Lucas; Hov, Karen Roksund; Berg, Jens Petter; Giil, Lasse Melvær & Nazmi, Arshed [Vis alle 12 forfattere av denne artikkelen] (2024). Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium. Brain, Behavior, and Immunity - Health (BBI - Health). 43, s. 1–13. doi: 10.1016/j.bbih.2024.100920. Fulltekst i vitenarkiv Vis sammendrag

  Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Qalbumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate de novo synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of Il1b, Tnfa, Cxcl1 and Ccl3 in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium.

• Aksnes, Mari; Edwin, Trine Holt; Saltvedt, Ingvild Tina; Eldholm, Rannveig Sakshaug; Chaudhry, Farrukh Abbas & Halaas, Nathalie Bodd [Vis alle 9 forfattere av denne artikkelen] (2023). Sex-specific associations of matrix metalloproteinases in Alzheimer’s disease. Biology of Sex Differences. 14(1). doi: 10.1186/s13293-023-00514-x. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Alzheimer’s disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-β (Aβ) and tau pathology. However, there is a need for biomarkers reflecting additional pathological pathways. Matrix metalloproteinases (MMPs) have recently been highlighted as candidate biomarkers for sex-specific mechanisms and progression in AD. Methods In this cross-sectional study, we investigated nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in the cerebrospinal fluid of 256 memory clinic patients with mild cognitive impairment or dementia due to AD and 100 cognitively unimpaired age-matched controls. We studied group differences in MMP/TIMP levels and examined the associations with established markers of Aβ and tau pathology as well as disease progression. Further, we studied sex-specific interactions. Results MMP-10 and TIMP-2 levels differed significantly between the memory clinic patients and the cognitively unimpaired controls. Furthermore, MMP- and TIMP-levels were generally strongly associated with tau biomarkers, whereas only MMP-3 and TIMP-4 were associated with Aβ biomarkers; these associations were sex-specific. In terms of progression, we found a trend towards higher MMP-10 at baseline predicting more cognitive and functional decline over time exclusively in women. Conclusion Our results support the use of MMPs/TIMPs as markers of sex differences and progression in AD. Our findings show sex-specific effects of MMP-3 and TIMP-4 on amyloid pathology. Further, this study highlights that the sex-specific effects of MMP-10 on cognitive and functional decline should be studied further if MMP-10 is to be used as a prognostic biomarker for AD.

• Titlestad, Irit; Watne, Leiv; Caplan, Gideon A.; McCann, Adrian; Ueland, Per Magne & Neerland, Bjørn Erik [Vis alle 15 forfattere av denne artikkelen] (2023). Impaired glucose utilization in the brain of patients with delirium following hip fracture. Brain. ISSN 0006-8950. 147(1), s. 215–223. doi: 10.1093/brain/awad296. Fulltekst i vitenarkiv Vis sammendrag

  Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and β-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, β-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium.

• Knapskog, Anne Brita; Aksnes, Mari; Edwin, Trine Holt; Ueland, Per Magne; Ulvik, Arve & Fang, Fei [Vis alle 11 forfattere av denne artikkelen] (2023). Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease. Alzheimer's & Dementia. ISSN 1552-5260. 19(12), s. 5573–5582. doi: 10.1002/alz.13162. Fulltekst i vitenarkiv Vis sammendrag

  INTRODUCTION The kynurenine pathway's (KP) malfunction is closely related to Alzheimer's disease (AD), for antagonistic kynurenic acid (KA) and agonistic quinolinic acid act on the N-methyl-D-aspartate receptor, a possible therapeutic target in treating AD. METHODS In our longitudinal case–control study, KP metabolites in the cerebrospinal fluid were analyzed in 311 patients with AD and 105 cognitively unimpaired controls. RESULTS Patients with AD exhibited higher concentrations of KA (β = 0.18, P < 0.01) and picolinic acid (β = 0.20, P < 0.01) than the controls. KA was positively associated with tau pathology (β = 0.29, P < 0.01), and a higher concentration of KA was associated with the slower progression of dementia. DISCUSSION The higher concentrations of neuroprotective metabolites KA and picolinic acid suggest that the activation of the KP's neuroprotective branch is an adaptive response in AD and may be a promising target for intervention and treatment. Highlights Patients with Alzheimer's disease (AD) exhibited higher concentrations of kynurenic acid and picolinic acid than controls. Higher concentrations of kynurenic acid were associated with slower progression of AD. Potential neurotoxic kynurenines were not increased among patients with AD. Activation of the kynurenine pathway's neuroprotective branch may be an adaptive response in AD.

• Aksnes, Mari; Capogna, Elettra; Vidal-Piñeiro, Didac; Chaudhry, Farrukh Abbas; Myrstad, Marius & Idland, Ane-Victoria [Vis alle 13 forfattere av denne artikkelen] (2023). Matrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals. Neurobiology of Aging. ISSN 0197-4580. 131, s. 11–23. doi: 10.1016/j.neurobiolaging.2023.05.012. Fulltekst i vitenarkiv Vis sammendrag

  Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer’s disease (AD), but their role in normal aging is poorly understood. We used linear mixed models to determine if baseline or rate of yearly change in cerebrospinal fluid (CSF) levels of MMP-2; MMP-3; MMP-10; TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3); or TIMP-4 predicted changes in bilateral entorhinal cortex thickness, hippocampal volume, or lateral ventricle volume in cognitively unimpaired individuals. We also assessed effects on the CSF AD biomarkers amyloid-β42 and phosphorylated tau181. Low baseline levels of MMP-3 predicted larger ventricle volumes and more entorhinal cortex thinning. Increased CSF MMP-2 levels over time predicted more entorhinal thinning, hippocampal atrophy, and ventricular expansion, while increased TIMP-123 over time predicted ventricular expansion. No MMP/TIMPs predicted changes in CSF AD biomarkers. Notably, we show for the first time that longitudinal increases in MMP-2 and TIMP-123 levels may predict age-associated brain atrophy. In conclusion, MMPs and TIMPs may play a role in brain atrophy in cognitively unimpaired aging.

• Dakhil, Shams; Saltvedt, Ingvild Tina; Benth, Jurate Saltyte; Thingstad, Anne Pernille Mæhle; Watne, Leiv & Wyller, Torgeir Bruun [Vis alle 10 forfattere av denne artikkelen] (2023). Longitudinal trajectories of functional recovery after hip fracture. PLOS ONE. 18(3). doi: 10.1371/journal.pone.0283551. Fulltekst i vitenarkiv Vis sammendrag

  Background There is limited evidence regarding predictors of functional trajectories after hip fracture. We aimed to identify groups with different trajectories of functional recovery the first year after hip fracture, and to determine predictors for belonging to such groups. Methods This longitudinal study combined data from two large randomized controlled trials including patients with hip fracture. Participants were assessed at baseline, four and 12 months. We used the Nottingham Extended Activities of Daily Living (NEADL) as a measure of instrumental ADL (iADL) and Barthel Index for personal ADL (pADL). A growth mixture model was estimated to identify groups of patients following distinct trajectories of functioning. Baseline characteristics potentially predicting group-belonging were assessed by multiple nominal regression. Results Among 726 participants (mean age 83.0; 74.7% women), we identified four groups of patients following distinct ADL trajectories. None of the groups regained their pre-fracture ADL. For one of the groups identified in both ADL outcomes, a steep decline in function was shown the first four months after surgery, and none of the groups showed functional recovery between four and 12 months after surgery. Conclusions No groups regained their pre-fracture ADL. Some of the patients with relatively high pre-fracture function, had a steep ADL decline. For this group there is a potential for recovery, but more knowledge and research is needed in this group. These findings could be useful in uncovering groups of patients with different functioning after a hip fracture, and aid in discharge planning.

• Fjell, Anders Martin; Sørensen, Øystein; Wang, Yunpeng; Amlien, Inge; Baaré, William F. C. & Bartrés-Faz, David [Vis alle 24 forfattere av denne artikkelen] (2023). No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy. Nature Human Behaviour. 7, s. 2008–2022. doi: 10.1038/s41562-023-01707-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-shaped relationships, where a duration of 6.5 (95% confidence interval, (5.7, 7.3)) hours was associated with the thickest cortex and largest volumes relative to intracranial volume. This fits converging evidence from research on mortality, health and cognition that points to roughly seven hours being associated with good health. Genome-wide association analyses suggested that genes associated with longer sleep for below-average sleepers were linked to shorter sleep for above-average sleepers. Mendelian randomization did not yield evidence for causal impacts of sleep on brain structure. The combined results challenge the notion that habitual short sleep causes brain atrophy, suggesting that normal brains promote adequate sleep duration—which is shorter than current recommendations.

• Capogna, Elettra; Watne, Leiv; Sørensen, Øystein; Guichelaar, Carlijn Jamila; Idland, Ane-Victoria & Halaas, Nathalie Bodd [Vis alle 11 forfattere av denne artikkelen] (2023). Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers – in cognitively unimpaired older adults. Brain, Behavior, and Immunity. ISSN 0889-1591. 113, s. 56–65. doi: 10.1016/j.bbi.2023.06.027. Fulltekst i vitenarkiv Vis sammendrag

  Concentrations of pro-inflammatory cytokines –interleukin-6 (IL-6) and interleukin-8 (IL-8) – are increased with age and in Alzheimer’s disease (AD). It is not clear whether concentrations of IL-6 and IL-8 in the central nervous system predict later brain and cognitive changes over time nor whether this relationship is mediated by core AD biomarkers. Here, 219 cognitively healthy older adults (62–91 years), with baseline cerebrospinal fluid (CSF) measures of IL-6 and IL-8 were followed over time – up to 9 years – with assessments that included cognitive function, structural magnetic resonance imaging, and CSF measurements of phosphorylated tau (p-tau) and amyloid-β (Aβ-42) concentrations (for a subsample). Higher baseline CSF IL-8 was associated with better memory performance over time in the context of lower levels of CSF p-tau and p-tau/Aβ-42 ratio. Higher CSF IL-6 was related to less CSF p-tau changes over time. The results are in line with the hypothesis suggesting that an up-regulation of IL-6 and IL-8 in the brain may play a neuroprotective role in cognitively healthy older adults with lower load of AD pathology.

• Fjell, Anders Martin; Sørensen, Øystein; Wang, Yunpeng; Amlien, Inge; Baaré, William F C & Bartrés-Faz, David [Vis alle 21 forfattere av denne artikkelen] (2023). Is Short Sleep Bad for the Brain? Brain Structure and Cognitive Function in Short Sleepers. Journal of Neuroscience. ISSN 0270-6474. 43(28), s. 5241–5250. doi: 10.1523/JNEUROSCI.2330-22.2023. Fulltekst i vitenarkiv Vis sammendrag

  Many sleep less than recommended without experiencing daytime sleepiness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this using a cross-sectional and longitudinal sample of 47,029 participants of both sexes (20–89 years) from the Lifebrain consortium, Human Connectome project (HCP) and UK Biobank (UKB), with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. A total of 740 participants who reported to sleep &lt;6 h did not experience daytime sleepiness or sleep problems/disturbances interfering with falling or staying asleep. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime sleepiness and sleep problems ( n = 1742) and participants sleeping the recommended 7–8 h ( n = 3886). However, both groups of short sleepers showed slightly lower general cognitive function (GCA), 0.16 and 0.19 SDs, respectively. Analyses using accelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income, and education. The results suggest that some people can cope with less sleep without obvious negative associations with brain morphometry and that sleepiness and sleep problems may be more related to brain structural differences than duration. However, the slightly lower performance on tests of general cognitive abilities warrants closer examination in natural settings. SIGNIFICANCE STATEMENT Short habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here, we show that daytime sleepiness and sleep problems are more strongly related to regional brain volumes than sleep duration. However, participants sleeping ≤6 h had slightly lower scores on tests of general cognitive function (GCA). This indicates that sleep need is individual and that sleep duration per se is very weakly if at all related brain health, while daytime sleepiness and sleep problems may show somewhat stronger associations. The association between habitual short sleep and lower scores on tests of general cognitive abilities must be further scrutinized in natural settings.

• Krogseth, Maria; Davis, Daniel; Jackson, Thomas A; Zetterberg, Henrik; Watne, Leiv & Lindberg, Morten [Vis alle 10 forfattere av denne artikkelen] (2023). Delirium, neurofilament light chain, and progressive cognitive impairment: analysis of a prospective Norwegian population-based cohort. The Lancet Healthy Longevity. 4(8), s. e399–e408. doi: 10.1016/S2666-7568(23)00098-3. Fulltekst i vitenarkiv Vis sammendrag

  Background: Previous population-based, longitudinal studies have shown that delirium is associated with an increased risk of dementia and cognitive decline. However, the underlying biological mechanisms are largely unknown. We aimed to assess the effects of delirium on both cognitive trajectories and any neuronal injury, measured via neurofilament light chain (NfL). Methods: In this analysis of a prospective, 2-year follow-up, cohort study of participants aged 65 years or older living in Sandefjord municipality, Norway, we included cohort participants who were receiving domiciliary care services at least once per week between May 12, 2015, and July 8, 2016. Individuals with a life expectancy of less than 1 week, with Lewy body dementia, with psychiatric illness (except dementia), or for whom substance misuse was the principal indication for domiciliary services were excluded. Participants had a comprehensive assessment at 6-month intervals for 2 years, which included the Montreal Cognitive Assessment (MoCA) and a blood sample for NfL to measure neuronal injury. All information on clinical diagnoses and medications were cross-referenced with medical records. During any acute change in mental status or hospitalisation (ie, admission to hospital), participants were assessed once per day for delirium with Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria. We also measured NfL from blood samples taken from participants who were acutely hospitalised. Findings: Between May 12, 2015, and July 8, 2016, 210 participants were eligible for inclusion and assessed at baseline (138 [66%] of whom were female and 72 [34%] of whom were male), 203 completed cognitive assessment, and 141 were followed up for 2 years. 160 (76%) of 210 had moderate or severe frailty and 112 (53%) were living with dementia. During the 2-year follow-up, 89 (42%) of 210 participants were diagnosed with one or more episodes of delirium. Incident delirium was independently associated with a decrease in MoCA score at the next 6-month follow-up, even after adjustment for age, sex, education, previous MoCA score, and frailty (adjusted mean difference –1·5, 95% CI –2·9 to –0·1). We found an interaction between previous MoCA score and delirium (β –0·254, 95% CI –0·441 to –0·066, p=0·010), with the largest decline being observed in people with better baseline cognition. Participants with delirium and good previous cognitive function and participants with a high peak concentration of NfL during any hospitalisation had increased NfL at the next 6-month follow-up. Mediation analyses showed independent pathways from previous MoCA score to follow-up MoCA score with contributions from incident delirium (–1·7, 95% CI –2·8 to –0·6) and from previous NfL to follow-up MoCA score with contributions from acute NfL concentrations (–1·8, –2·5 to –1·1). Delirium was directly linked with a predicted value of 1·2 pg/mL (95% CI 1·02 to 1·40, p=0·029) increase in NfL. Interpretation: In people aged 65 years or older, an episode of delirium was associated with a decline in MoCA score. Greater neuronal injury during acute illness and delirium, measured by NfL, was associated with greater cognitive decline. For clinicians, our finding of delirium associated with both signs of acute neuronal injury, measured via NfL, and cognitive decline is important regarding the risk of long-term cognitive deterioration and to acknowledge that delirium is harmful for the brain.

• Solvang, Stein-Erik Hafstad; Hodge, Allison; Watne, Leiv; Cabral-Marques, Otavio; Nordrehaug, Jan Erik & Giles, Graham G. [Vis alle 16 forfattere av denne artikkelen] (2022). Kynurenine Pathway Metabolites in the Blood and Cerebrospinal Fluid Are Associated with Human Aging. Oxidative Medicine and Cellular Longevity. ISSN 1942-0900. 2022, s. 1–15. doi: 10.1155/2022/5019752. Fulltekst i vitenarkiv Vis sammendrag

  The kynurenine pathway is implicated in aging, longevity, and immune regulation, but longitudinal studies and assessment of the cerebrospinal fluid (CSF) are lacking. We investigated tryptophan (Trp) and downstream kynurenine metabolites and their associations with age and change over time in four cohorts using comprehensive, targeted metabolomics. The study included 1574 participants in two cohorts with repeated metabolite measurements (mean age at baseline and ), 3161 community-dwelling older adults (age range 71-74 years), and 109 CSF donors (mean age ). In the first two cohorts, age was associated with kynurenine (Kyn), quinolinic acid (QA), and the kynurenine to tryptophan ratio (KTR), and inversely with Trp. Consistent with these findings, Kyn, QA, and KTR increased over time, whereas Trp decreased. Similarly, QA and KTR were higher in community-dwelling older adults of age 74 compared to 71, whereas Trp was lower. Kyn and QA were more strongly correlated with age in the CSF compared to serum and increased in a subset of participants with repeated CSF sampling () over four years. We assessed associations with frailty and mortality in two cohorts. QA and KTR were most strongly associated with mortality and frailty. Our study provides robust evidence of changes in tryptophan and kynurenine metabolism with human aging and supports links with adverse health outcomes. Our results suggest that aging activates the inflammation and stress-driven kynurenine pathway systemically and in the brain, but we cannot determine whether this activation is harmful or adaptive. We identified a relatively stronger age-related increase of the potentially neurotoxic end-product QA in brain.

• Watne, Leiv Otto; Pollmann, Christian Thomas; Neerland, Bjørn Erik; Paulsen, Else Quist; Halaas, Nathalie Bodd & Idland, Ane-Victoria [Vis alle 20 forfattere av denne artikkelen] (2022). Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip-fracture patients. Journal of Clinical Investigation. ISSN 0021-9738. 133(2). doi: 10.1172/JCI163472. Fulltekst i vitenarkiv Vis sammendrag

  Background: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanism underlying delirium, particularly in relation to the KP, remain elusive. Methods: We undertook a multi-center observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and one-year mortality. Results: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA, OR 2.26 [1.78, 2.87], p

• Vidal-Piñeiro, Didac; Sørensen, Øystein; Blennow, Kaj; Capogna, Elettra; Halaas, Nathalie Bodd & Idland, Ane-Victoria [Vis alle 12 forfattere av denne artikkelen] (2022). Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults. Neurobiology of Aging. ISSN 0197-4580. 116, s. 80–91. doi: 10.1016/j.neurobiolaging.2022.04.010. Fulltekst i vitenarkiv Vis sammendrag

  It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-β (Aβ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3)=, total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by Aβ42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers.

• Page, Valerie J; Watne, Leiv; Heslegrave, Amanda; Clark, Allan; McAuley, Daniel F & Sanders, Robert D [Vis alle 7 forfattere av denne artikkelen] (2022). Plasma neurofilament light chain protein as a predictor of days in delirium and deep sedation, mortality and length of stay in critically ill patients. EBioMedicine. 80. doi: 10.1016/j.ebiom.2022.104043. Fulltekst i vitenarkiv
• Henjum, Kristi; Watne, Leiv; Godang, Kristin; Halaas, Nathalie Bodd; Eldholm, Rannveig Sakshaug & Blennow, Kaj [Vis alle 10 forfattere av denne artikkelen] (2022). Cerebrospinal fluid catecholamines in Alzheimer's disease patients with and without biological disease. Translational Psychiatry. 12. doi: 10.1038/s41398-022-01901-5. Fulltekst i vitenarkiv Vis sammendrag

  Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer’s disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; n = 54) or dementia stage (n = 240) and in cognitively unimpaired (n = 113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (n = 294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (n = 113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and APOEε4 status verified the findings. In restricted analyses comparing A+T+ patients to A−T− cognitively unimpaired, the findings for CSF adrenaline remained significant (p < 0.001) but not for CSF noradrenaline (p = 0.07) and CSF dopamine (p = 0.33). There were no differences between A+T+ and A−T− cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin.

• Halaas, Nathalie Bodd; Zetterberg, Henrik; Idland, Ane-Victoria; Knapskog, Anne Brita; Watne, Leiv Otto & Blennow, Kaj (2021). Cerebrospinal Fluid Concentration of Neurogranin in Hip Fracture Patients with Delirium. Journal of Alzheimer's Disease. ISSN 1387-2877. 81(2), s. 1–28. doi: 10.3233/jad-201341. Fulltekst i vitenarkiv
• Wang, Yunpeng; Grydeland, Håkon; Roe, James Michael; Pan, Mengyu; Magnussen, Fredrik & Amlien, Inge [Vis alle 17 forfattere av denne artikkelen] (2021). Associations of circulating C-reactive proteins, APOE ε4, and brain markers for Alzheimer’s disease in healthy samples across the lifespan. Brain, Behavior, and Immunity. ISSN 0889-1591. 100. doi: 10.1016/j.bbi.2021.12.008. Fulltekst i vitenarkiv Vis sammendrag

  The apolipoprotein E gene ε4 allele (APOE ε4) and higher circulating level of C-reactive protein (CRP) have been extensively investigated as risk factors for Alzheimer’s disease (AD). Paradoxically, APOE ε4 has been associated with lower levels of blood CRP in middle-aged and older populations. However, few studies have investigated this intriguing relation and its impact on neurological markers for AD in younger ages, nor across the whole lifespan. Here, we examine associations of blood CRP levels, APOE ε4, and biomarkers for AD in a cognitively healthy lifespan cohort (N up to 749; 20–81 years of age) and replicate the findings in UK Biobank (N = 304 322; 37–72 years of age), the developmental ABCD study (N = 10 283; 9–11 years of age), and a middle-aged sample (N = 339; 40–65 years of age). Hippocampal volume, brain amyloid-β (Aβ) plaque levels, cerebrospinal fluid (CSF) levels of Aβ and tau species, and neurofilament protein light protein (NFL) were used as AD biomarkers in subsamples. In addition, we examined the genetic contribution to the variation of CRP levels over different CRP ranges using polygenic scores for CRP (PGS-CRP). Our results show APOE ε4 consistently associates with low blood CRP levels across all age groups (p < 0.05). Strikingly, both ε4 and PGS-CRP associated mainly with blood CRP levels within the low range (<5mg/L). We then show both APOE ε4 and high CRP levels associate with smaller hippocampus volumes across the lifespan (p < 0.025). APOE ε4 was associated with high Aβ plaque levels in the brain (FDR-corrected p = 8.69x10-4), low levels of CSF Aβ42 (FDR-corrected p = 6.9x10-2), and lower ratios of Aβ42 to Aβ40 (FDR-corrected p = 5.08x10-5). Blood CRP levels were weakly correlated with higher ratio of CSF Aβ42 to Aβ40 (p = 0.03, FDR-corrected p = 0.4). APOE ε4 did not correlate with blood concentrations of another 9 inflammatory cytokines, and none of these cytokines correlated with AD biomarkers.

• Dakhil, Shams; Thingstad, Pernille; Frihagen, Frede; Johnsen, Lars Gunnar; Lydersen, Stian & Skovlund, Eva [Vis alle 10 forfattere av denne artikkelen] (2021). Orthogeriatrics prevents functional decline in hip fracture patients: report from two randomized controlled trials. BMC Geriatrics. 21(208). doi: 10.1186/s12877-021-02152-7. Fulltekst i vitenarkiv Vis sammendrag

  Background The incidence of hip fractures are expected to increase in the following years. Hip fracture patients have in addition to their fracture often complex medical problems, which constitute a substantial burden on society and health care systems. It is thus important to optimize the treatment of these patients to reduce negative outcomes. The aim of this study was to assess the effect of comprehensive orthogeriatric care (CGC) on basic and instrumental activities of daily living (B-ADL and I-ADL). Methods This study is based on two randomized controlled trials; the Oslo Orthogeriatric Trial and the Trondheim Hip Fracture Trial. The two studies were planned in concert, and data were pooled and analyzed using linear mixed models. I-ADL function was assessed by the Nottingham Extended ADL Scale (NEADL) and B-ADL by the Barthel ADL (BADL) at four and twelve months after surgery. Results Seven hundred twenty-six patients were included in the combined database, of which 365 patients received OC and 361 patients received CGC. For the primary endpoint, I-ADL at four months was better in the CGC group, with a between-group difference of 3.56 points (95 % CI 0.93 to 6.20, p = 0.008). The between-group difference at 12 months was 4.28 points (95 % CI 1.57 to 7.00, p = 0.002). For B-ADL, between-group difference scores were only statistically significant at 12 months. When excluding the patients living at a nursing home at admission, both I-ADL and B-ADL function was significantly better in the CGC group compared to the OC group at all time points. Conclusions Merged data of two randomized controlled trials showed that admitting hip fracture patients to an orthogeriatric care unit directly from the emergency department had a positive effect on ADL up to twelve months after surgery.

• Henjum, Kristi; Godang, Kristin; Quist-Paulsen, Else; Idland, Ane-Victoria; Neerland, Bjørn Erik & Sandvig, Heidi Vihovde [Vis alle 13 forfattere av denne artikkelen] (2021). Cerebrospinal fluid catecholamines in delirium and dementia. Brain Communications. 3(3), s. 1–11. doi: 10.1093/braincomms/fcab121. Fulltekst i vitenarkiv Vis sammendrag

  Dopamine and noradrenaline are functionally connected to delirium and have been targets for pharmacological interventions but the biochemical evidence to support this notion is limited. To study the CSF levels of dopamine, noradrenaline and the third catecholamine adrenaline in delirium and dementia, these were quantified in three patient cohorts: (i) cognitively normal elderly patients (n¼122); (ii) hip fracture patients with or without delirium and dementia (n¼118); and (iii) patients with delirium precipitated by another medical condition (medical delirium, n¼26). Delirium was assessed by the Confusion Assessment Method. The hip fracture cohort had higher CSF levels of noradrenaline and adrenaline than the two other cohorts (both P<0.001). Within the hip fracture cohort those with delirium (n¼65) had lower CSF adrenaline and dopamine levels than those without delirium (n¼52, P¼0.03, P¼0.002). Similarly, the medical delirium patients had lower CSF dopamine levels than the cognitively normal elderly (P<0.001). Age did not correlate with the CSF catecholamine levels. These findings with lower CSF dopamine levels in hip fracture- and medical delirium patients challenge the theory of dopamine excess in delirium and question use of antipsychotics in delirium. The use of alpha-2 agonists with the potential to reduce noradrenaline release needs further examination.

• Sandvik, Miriam Kristine; Watne, Leiv; Brugård, Anniken; Wang-Hansen, Marte Sofie & Kersten, Hege (2021). Association between psychotropic drug use and handgrip strength in older hospitalized patients. European Geriatric Medicine. ISSN 1878-7649. 12(6), s. 1213–1220. doi: 10.1007/s41999-021-00511-6. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: Handgrip strength is an indicator of frailty and longevity in older adults. The association between psychotropic drug use and handgrip strength in older hospitalized patients was investigated in this study. Methods: A total of 488 patients were included in this retrospective cross-sectional study, 333 women and 155 men, from two different cohorts of older (mean age 84 years) hospitalized in-patients. We used multiple linear regression models to explore the association between psychotropic drug use and handgrip strength. We adjusted for factors known to affect handgrip strength: Age, gender, body mass index (BMI) and comorbidity (Charlson comorbidity index). Results: Both unadjusted and adjusted analyses showed that psychotropic drug use was associated with handgrip strength (β = - 0.183, p

• Ernst, Gernot Walter; Watne, Leiv Otto; Frihagen, Frede; Wyller, Torgeir Bruun; Dominik, Andreas & Rostrup, Morten (2021). Low Heart Rate Variability Predicts Stroke and Other Complications in the First Six Postoperative Months After a Hip Fracture Operation. Frontiers in Cardiovascular Medicine. 8, s. 1–8. doi: 10.3389/fcvm.2021.640970. Fulltekst i vitenarkiv
• Pollmann, Christian Thomas; Mellingsæter, Marte; Neerland, Bjørn Erik; Straume-Næsheim, Truls Martin; Årøen, Asbjørn & Watne, Leiv (2021). Orthogeriatric co-management reduces incidence of delirium in hip fracture patients. Osteoporosis International. ISSN 0937-941X. 32, s. 2225–2233. doi: 10.1007/s00198-021-05974-8. Fulltekst i vitenarkiv Vis sammendrag

  Summary: Hip fracture patients often display an acute confusional state (delirium) which is associated with worse outcomes. In this observational study, we found that co-management of hip fracture patients by a multidisciplinary team including a geriatrician and an orthopaedic surgeon could reduce the incidence of delirium. Introduction: Delirium after hip fracture is common and is associated with negative outcomes. We investigated if orthogeriatric co-management reduced the incidence of delirium in hip fracture patients. Methods: In this single-centre, prospective observational study, we compared the incidence of delirium and subsyndromal delirium (SSD) before (usual care group, n = 94) and after (orthogeriatric group, n = 103) the introduction of orthogeriatric co-management as an integrated care model. The outcome measure ‘no delirium/SSD/delirium’ was treated as an ordinal variable and analysed using the chi-squared test and multivariable ordinal logistic regression. Results: The groups had similar baseline characteristics except for a higher proportion of patients with pre-existing cognitive impairment in the usual care group (51% vs. 37%, p = 0.045). Fewer patients in the orthogeriatric group developed SSD or delirium (no delirium: 59% vs. 40%/SSD: 6% vs. 13%/delirium: 35% vs. 47%; p = 0.021). The number needed to treat (NNT) to avoid one case of SSD or delirium was 5.3 (95% CI: 3.1 to 19.7). In a multivariable analysis adjusted for age, sex, ASA class, pre-existing cognitive impairment, time to surgery, type of surgery, and medical or surgical complications, the odds ratio for the development of SSD/delirium was lower in the orthogeriatric group (OR = 0.46, 95% CI: 0.23–0.89, p = 0.023). Conclusion: Orthogeriatric co-management as an integrated care model reduced the incidence of SSD/delirium in hip fracture patients.

• Raheel, Tayyaba Qureshi; Bjørkmo, Mona; Nordengen, Kaja; Gundersen, Vidar; Utheim, Tor Paaske & Watne, Leiv Otto [Vis alle 9 forfattere av denne artikkelen] (2020). Slc38a1 Conveys Astroglia-Derived Glutamine into GABAergic Interneurons for Neurotransmitter GABA Synthesis. Cells. 9(7), s. 1–12. doi: 10.3390/cells9071686. Fulltekst i vitenarkiv Vis sammendrag

  GABA signaling is involved in a wide range of neuronal functions, such as synchronization of action potential firing, synaptic plasticity and neuronal development. Sustained GABA signaling requires efficient mechanisms for the replenishment of the neurotransmitter pool of GABA. The prevailing theory is that exocytotically released GABA may be transported into perisynaptic astroglia and converted to glutamine, which is then shuttled back to the neurons for resynthesis of GABA—i.e., the glutamate/GABA-glutamine (GGG) cycle. However, an unequivocal demonstration of astroglia-to-nerve terminal transport of glutamine and the contribution of astroglia-derived glutamine to neurotransmitter GABA synthesis is lacking. By genetic inactivation of the amino acid transporter Solute carrier 38 member a1 (Slc38a1)—which is enriched on parvalbumin+ GABAergic neurons—and by intraperitoneal injection of radiolabeled acetate (which is metabolized to glutamine in astroglial cells), we show that Slc38a1 mediates import of astroglia-derived glutamine into GABAergic neurons for synthesis of GABA. In brain slices, we demonstrate the role of Slc38a1 for the uptake of glutamine specifically into GABAergic nerve terminals for the synthesis of GABA depending on demand and glutamine supply. Thus, while leaving room for other pathways, our study demonstrates a key role of Slc38a1 for newly formed GABA, in harmony with the existence of a GGG cycle.

• Sajjad, Muhammad Umar; Blennow, Kaj; Knapskog, Anne Brita; Idland, Ane-Victoria; Chaudhry, Farrukh Abbas & Wyller, Torgeir Bruun [Vis alle 8 forfattere av denne artikkelen] (2020). Cerebrospinal Fluid Levels of Interleukin-8 in Delirium, Dementia, and Cognitively Healthy Patients. Journal of Alzheimer's Disease. ISSN 1387-2877. 73(4), s. 1363–1372. doi: 10.3233/JAD-190941. Fulltekst i vitenarkiv Vis sammendrag

  Background: Delirium is a common and serious complication in geriatric patients. The pathophysiology of delirium is not known. Objective: The objective of the current study was to test the hypothesis that cerebrospinal fluid (CSF) levels of inflammatory markers at the time of spinal anesthesia for hip surgery are associated with delirium. Methods: In total 133 hip fracture patients and 125 cognitively healthy controls undergoing elective surgery, together with 73 Alzheimer’s disease (AD) dementia patients, were recruited at Oslo University Hospital and Diakonhjemmet Hospital, Oslo, Norway. Delirium was evaluated daily in hip fracture patients by the Confusion Assessment Method (CAM). Depression was evaluated by Cornell Scale for Depression in Dementia (CSDD). Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-8 (IL-8) levels were measured in CSF using a Mesoscale Discovery (MSD) immunoassay. Results: Hip fracture patients had significantly higher IL-8 levels (p < 0.001) compared to cognitively healthy controls or patients with stable AD dementia. Furthermore, preoperative IL-8 levels were significantly higher (p = 0.013) in hip fracture patients who developed delirium (incident delirium) after surgery as compared to patients with no delirium. However, subgroup analyses showed that IL-8 levels were only significantly higher in delirium patients without dementia (p = 0.006). In contrast, depression subgroup analysis showed that IL-8 concentration was significantly higher (p = 0.002) in delirium patients with depression. Both TNF-α and IL-1β were undetected in most patients. Conclusions: Our study suggests that IL-8 levels are associated with delirium onset and that underlying depression or dementia influences IL-8 levels.

• Walhovd, Kristine B; Fjell, Anders Martin; Sørensen, Øystein; Mowinckel, Athanasia Monika; Reinbold, Céline Sonja & Idland, Ane-Victoria [Vis alle 12 forfattere av denne artikkelen] (2020). Genetic risk for Alzheimer disease predicts hippocampal volume through the human lifespan. Neurology: Genetics. 6(5). doi: 10.1212/NXG.0000000000000506. Fulltekst i vitenarkiv Vis sammendrag

  Objective To test the hypothesis that genetic risk for Alzheimer disease (AD) may represent a stable influence on the brain from early in life, rather than being primarily age dependent, we investigated in a lifespan sample of 1,181 persons with a total of 2,690 brain scans, whether higher polygenic risk score (PGS) for AD and presence of APOE ε4 was associated with lower hippocampal volumes to begin with, as an offset effect, or possibly faster decline in older age. Methods Using general additive mixed models, we assessed the relations of PGS for AD, including variants in APOE with hippocampal volume and its change in a cognitively healthy longitudinal lifespan sample (age range: 4–95 years, mean visit age 39.7 years, SD 26.9 years), followed for up to 11 years. Results AD-PGS and APOE ε4 in isolation showed a significant negative effect on hippocampal volume. The effect of a 1 sample SD increase in AD-PGS on hippocampal volume was estimated to –36.4 mm 3 (confidence interval [CI]: –71.8, –1.04) and the effect of carrying ε4 allele(s) –107.0 mm 3 (CI: –182.0, –31.5). Offset effects of AD-PGS and APOE ε4 were present in hippocampal development, and interactions between age and genetic risk on volume change were not consistently observed. Conclusions Endophenotypic manifestation of polygenic risk for AD may be seen across the lifespan in cognitively healthy persons, not being confined to clinical populations or older age. This emphasizes that a broader population and age range may be relevant targets for attempts to prevent AD.

• Idland, Ane-Victoria; Llonch, Roser Sala; Watne, Leiv; Brækhus, Anne; Hansson, Oskar & Blennow, Kaj [Vis alle 11 forfattere av denne artikkelen] (2020). Biomarker Profiling Beyond Amyloid and Tau: Cerebrospinal Fluid Markers, Hippocampal Atrophy, and Memory Change in Cognitively Unimpaired Older Adults. Neurobiology of Aging. ISSN 0197-4580. 93, s. 1–15. doi: 10.1016/j.neurobiolaging.2020.04.002. Fulltekst i vitenarkiv Vis sammendrag

  Brain changes occurring in aging can be indexed by biomarkers. We used cluster analysis to identify subgroups of cognitively unimpaired individuals (n = 99, 64-93 years) with different profiles of the cerebrospinal fluid biomarkers beta amyloid 1-42 (Aβ42), phosphorylated tau (P-tau), total tau, chitinase-3-like protein 1 (YKL-40), fatty acid binding protein 3 (FABP3), and neurofilament light (NFL). Hippocampal volume and memory were assessed across multiple follow-up examinations covering up to 6.8 years. Clustering revealed one group (39%) with more pathological concentrations of all biomarkers, which could further be divided into one group (20%) characterized by tauopathy and high FABP3 and one (19%) by brain β-amyloidosis, high NFL, and slightly higher YKL-40. The clustering approach clearly outperformed classification based on Aβ42 and P-tau alone in prediction of memory decline, with the individuals with most tauopathy and FABP3 showing more memory decline, but not more hippocampal volume change. The results demonstrate that older adults can be classified based on biomarkers beyond amyloid and tau, with improved prediction of memory decline

• Ernst, Gernot; Watne, Leiv; Rostrup, Morten & Neerland, Bjørn Erik (2020). Delirium in patients with hip fracture is associated with increased heart rate variability. Aging Clinical and Experimental Research. ISSN 1594-0667. 32, s. 2311–2318. doi: 10.1007/s40520-019-01447-5. Fulltekst i vitenarkiv
• Edwin, Trine Holt; Henjum, Kristi; Nilsson, Lars; Watne, Leiv; Persson, Karin Ester Torun & Eldholm, Rannveig Sakshaug [Vis alle 12 forfattere av denne artikkelen] (2020). A high cerebrospinal fluid soluble TREM2 level is associated with slow clinical progression of Alzheimer's disease. Alzheimer's & Dementia. ISSN 1552-5260. 12(1). doi: 10.1002/dad2.12128. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: The progression rate of Alzheimer's disease (AD) varies and might be affected by the triggering receptor expressed on myeloid cells (TREM2) activity. We explored if cerebrospinal fluid (CSF) soluble TREM2 (sTREM2), a proxy of microglial activity, is associated with clinical progression rate. Methods: Patients with clinical AD (N = 231) were followed for up to 3 years after diagnosis. Cognitively healthy controls (N = 42) were followed for 5 years. CSF sTREM2 was analyzed by enzyme-linked immunosorbent assay. Group-based trajectory modeling revealed distinct clinical progression groups. Results: Higher CSF sTREM2 was associated with slow clinical progression. The slow- and medium-progressing groups had higher CSF sTREM2 than the cognitively healthy, who had a similar level to patients with rapid clinical progression. Discussion: CSF sTREM2 levels were associated with clinical progression in AD, regardless of core biomarkers. This could be useful in assessing disease development in relation to patient care and clinical trial recruitment. Keywords: Alzheimer's disease; Clinical Dementia Rating scale; disease progression; soluble triggering receptor expressed on myeloid cells 2 (sTREM2); trajectories.

• Fjell, Anders Martin; Sederevicius, Donatas; Sneve, Markus Handal; Lange, Ann-Marie Glasø de; Bråthen, Anne Cecilie Sjøli & Idland, Ane-Victoria [Vis alle 16 forfattere av denne artikkelen] (2020). Self-reported sleep problems are related to amyloid deposition in cortical regions with high HOMER1 gene expression. Cerebral Cortex. ISSN 1047-3211. 30(4), s. 2144–2156. doi: 10.1093/cercor/bhz228. Fulltekst i vitenarkiv Vis sammendrag

  Sleep problems are related to the elevated levels of the Alzheimer’s disease (AD) biomarker β-amyloid (Aβ). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aβ accumulation. Here, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aβ correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aβ relationship followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aβ accumulation may involve Homer1 activity in the cortical regions, where harbor Aβ deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

• Fjell, Anders Martin; Sørensen, Øystein; Amlien, Inge Kasbohm; Bartrés-Faz, David; Brandmaier, Andreas M. & Buchmann, Nikolaus [Vis alle 32 forfattere av denne artikkelen] (2020). Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium. Cerebral Cortex. ISSN 1047-3211. s. 1–17. doi: 10.1093/cercor/bhaa332. Fulltekst i vitenarkiv Vis sammendrag

  We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18–92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. “PSQI # 1 Subjective sleep quality” and “PSQI #5 Sleep disturbances” were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with “PSQI #5 Sleep disturbances” emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

• Kealy, John; Murray, Carol; Griffin, Eadaoin W.; Lopez-Rodriguez, Ana Belen; Healy, Dáire & Tortorelli, Lucas Silva [Vis alle 9 forfattere av denne artikkelen] (2020). Acute inflammation alters brain energy metabolism in mice and humans: Role in suppressed spontaneous activity, impaired cognition, and delirium. Journal of Neuroscience. ISSN 0270-6474. 40(29), s. 5681–5696. doi: 10.1523/JNEUROSCI.2876-19.2020. Fulltekst i vitenarkiv
• Neerland, Bjørn Erik; Halaas, Nathalie Bodd; Idland, Ane-Victoria; Henjum, Kristi; Blennow, Kaj & Zetterberg, Henrik [Vis alle 7 forfattere av denne artikkelen] (2020). Fatty Acid-Binding Protein 3 in Cerebrospinal Fluid of Hip Fracture Patients with Delirium. Journal of Alzheimer's Disease. ISSN 1387-2877. 77(1), s. 183–190. doi: 10.3233/JAD-200364. Fulltekst i vitenarkiv Vis sammendrag

  Background: Delirium is associated with dementia and thus biomarkers reflecting neurodegeneration are of interest. Fatty acid-binding protein 3 (FABP3) is a cytoplasmic neuronal protein that has been isolated from the brain. It is released following brain injury and concentrations in cerebrospinal fluid (CSF) are also higher in neurodegenerative disorders such as Alzheimer’s disease (AD). Objective: To examine the relationship between CSF FABP3 concentration and delirium in hip fracture patients compared to a group of cognitively normal controls. Methods: CFS FABP3 concentration was measured in 128 hip fracture patients with (n = 71) and without (n = 57) delirium, and in cognitively unimpaired adults ≥64 years (n = 124) undergoing elective surgery. Results: CSF FABP3 (pg/ml) concentration (median (IQR)) was higher in hip-fracture patients compared to cognitively normal controls (5.7 (4.2–7.7) versus 4.5 (3.4–6.1), p &lt; 0.001). There was a significant weak correlation between age and CSF FABP3 (ρ= 0.3, p &lt; 0.001). After adjustment for age, the association between CSF FABP3 and hip-fracture was no longer statistically significant (β= 0.05, p = 0.5). There were no significant differences in CSF FABP3 concentration between hip fracture patients with (5.4 (4.1–8.2)) and without (5.8 (4.2–7.2)) delirium. CSF FABP3 concentration correlated positively with CSF AD biomarkers p-tau (ρ= 0.7, p &lt; 0.01) and t-tau (ρ= 0.7, p &lt; 0.01). Conclusion: CSF FABP3 concentrations were higher in hip fracture patients compared with cognitively normal older adults, indicating ongoing age-related neurodegeneration in these patients. There were no differences of CSF FABP3 concentrations across delirium groups, suggesting that neuronal damage or degeneration reflected by FABP3 may not be directly linked to delirium pathophysiology.

• Gorbach, Tetiana; Pudas, Sara; Bartrés-Faz, David; Brandmaier, Andreas M.; Düzel, Sandra & Henson, Rik [Vis alle 17 forfattere av denne artikkelen] (2020). Longitudinal association between hippocampus atrophy and episodic‐memory decline in non‐demented APOE ε4 carriers. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. 12(1). doi: 10.1002/dad2.12110. Fulltekst i vitenarkiv Vis sammendrag

  Introduction The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic‐memory decline in non‐demented individuals remains unclear. Methods We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)–derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European Lifebrain consortium. Results The change‐change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, P = .007; non‐carriers: N = 467, r = 0.073, P = .117). The linear relationship was significantly steeper for the carriers [t(629) = 2.4, P = .013]. A similar trend toward a stronger change‐change relation for carriers was seen in a subsample with more than two assessments. Discussion These findings provide evidence for a difference in hippocampus‐memory association between ε4 carriers and non‐carriers, thus highlighting how genetic factors modulate the translation of the AD‐related pathophysiological cascade into cognitive deficits.

• Svenøy, Stian; Watne, Leiv; Hestnes, Ingvild; WESTBERG, MARIANNE; Madsen, Jan Erik & Frihagen, Frede Jon (2020). Results after introduction of a hip fracture care pathway: comparison with usual care. Acta Orthopaedica. ISSN 1745-3674. 91(2), s. 139–145. doi: 10.1080/17453674.2019.1710804. Fulltekst i vitenarkiv
• Knapskog, Anne Brita; Henjum, Kristi; Idland, Ane-Victoria; Eldholm, Rannveig Sakshaug; Persson, Karin Ester Torun & Saltvedt, Ingvild [Vis alle 9 forfattere av denne artikkelen] (2020). Cerebrospinal fluid sTREM2 in Alzheimer’s disease: comparisons between clinical presentation and AT classification. Scientific Reports. 10, s. 1–10. doi: 10.1038/s41598-020-72878-8. Fulltekst i vitenarkiv Vis sammendrag

  Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia. Its cleaved fragments, soluble TREM2 (sTREM2), can be measured in the cerebrospinal fluid (CSF). Previous studies indicate higher CSF sTREM2 in symptomatic AD; however most of these studies have included biomarker positive AD cases and biomarker negative controls. The aim of the study was to explore potential differences in the CSF level of sTREM2 and factors associated with an increased sTREM2 level in patients diagnosed with mild cognitive impairment (MCI) or dementia due to AD compared with cognitively unimpaired controls as judged by clinical symptoms and biomarker category (AT). We included 299 memory clinic patients, 62 (20.7%) with AD-MCI and 237 (79.3%) with AD dementia, and 113 cognitively unimpaired controls. CSF measures of the core biomarkers were applied to determine AT status. CSF sTREM2 was analyzed by ELISA. Patients presented with comparable CSF sTREM2 levels as the cognitively unimpaired (9.6 ng/ml [SD 4.7] versus 8.8 ng/ml [SD 3.6], p = 0.27). We found that CSF sTREM2 associated with age-related neuroinflammation and tauopathy irrespectively of amyloid β, APOE ε4 status or gender. The findings were similar in both symptomatic and non-symptomatic individuals.

• Fjell, Anders Martin; Sørensen, Øystein; Amlien, Inge Kasbohm; Bartrés-Faz, David; Bros, Didac Macia & Buchmann, Nikolaus [Vis alle 28 forfattere av denne artikkelen] (2019). Self-reported sleep relates to hippocampal atrophy across the adult lifespan – results from the Lifebrain consortium. Sleep. ISSN 0161-8105. doi: 10.1093/sleep/zsz280. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan. Methods Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18-90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21390 participants from the UK Biobank. Results No cross-sectional sleep – hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses. Conclusions Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.

• Halaas, Nathalie Bodd; Henjum, Kristi; Blennow, Kaj; Dakhil, Shams; Idland, Ane-Victoria & Nilsson, Lars [Vis alle 13 forfattere av denne artikkelen] (2019). CSF sTREM2 and Tau Work Together in Predicting Increased Temporal Lobe Atrophy in Older Adults. Cerebral Cortex. ISSN 1047-3211. 00, s. 1–12. doi: 10.1093/cercor/bhz240. Fulltekst i vitenarkiv Vis sammendrag

  Neuroinflammation may be a key factor in brain atrophy in aging and age-related neurodegenerative disease. The objective of this study was to test the association between microglial expression of soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2), as a measure of neuroinflammation, and brain atrophy in cognitively unimpaired older adults. Brain magnetic resonance imagings (MRIs) and cerebrospinal fluid (CSF) sTREM2, total tau (t-tau), phosphorylated181 tau (p-tau), and Aβ42 were analyzed in 115 cognitively unimpaired older adults, classified according to the A/T/(N)-framework. MRIs were repeated after 2 (n = 95) and 4 (n = 62) years. High baseline sTREM2 was associated with accelerated cortical thinning in the temporal cortex of the left hemisphere, as well as bilateral hippocampal atrophy, independently of age, Aβ42, and tau. sTREM2-related atrophy only marginally increased with biomarker positivity across the AD continuum (A−T− #x2292; A+T− #x2292; A+T+) but was significantly stronger in participants with a high level of p-tau (T+). sTREM2-related cortical thinning correlated significantly with areas of high microglial-specific gene expression in the Allen Human Brain Atlas. In conclusion, increased CSF sTREM2 was associated with accelerated cortical and hippocampal atrophy in cognitively unimpaired older participants, particularly in individuals with tau pathology. This suggests a link between neuroinflammation, neurodegeneration, and amyloid-independent tauopathy.

• Myrstad, Marius; Watne, Leiv; Johnsen, Nina T.; Børs-Lind, Emma & Neerland, Bjørn Erik (2019). Delirium screening in an acute geriatric ward by nurses using 4AT: results from a quality improvement project. European Geriatric Medicine. ISSN 1878-7649. 10(4), s. 667–671. doi: 10.1007/s41999-019-00215-y. Fulltekst i vitenarkiv
• Leavey, Nick; Hammond, Simon P; Shepstone, Lee; Cross, Jane; Zetterberg, Henrik & Cunningham, Colm [Vis alle 15 forfattere av denne artikkelen] (2019). Study protocol: ASCRIBED: the impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in dementia: A study in acute hip fracture patients. BMC Neurology. 19(1). doi: 10.1186/s12883-019-1447-7. Fulltekst i vitenarkiv
• Hall, Roanna J.; Watne, Leiv; Cunningham, Emma; Zetterberg, Henrik; Shenkin, Susan D & Wyller, Torgeir Bruun [Vis alle 7 forfattere av denne artikkelen] (2018). CSF biomarkers in delirium: a systematic review. International Journal of Geriatric Psychiatry. ISSN 0885-6230. 33(11), s. 1479–1500. doi: 10.1002/gps.4720. Fulltekst i vitenarkiv
• Watne, Leiv Otto & Wyller, Torgeir Bruun (2018). Delirium - framleis underdiagnostisert. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(5). doi: 10.4045/tidsskr.18.0118. Fulltekst i vitenarkiv
• Halaas, Nathalie Bodd; Blennow, Kaj; Idland, Ane-Victoria; Wyller, Torgeir Bruun; Ræder, Johan & Frihagen, Frede Jon [Vis alle 9 forfattere av denne artikkelen] (2018). Neurofilament light in serum and cerebrospinal fluid of hip fracture patients with delirium. Dementia and Geriatric Cognitive Disorders. ISSN 1420-8008. 46(5-6), s. 346–357. doi: 10.1159/000494754. Fulltekst i vitenarkiv Vis sammendrag

  Background: Delirium is associated with new-onset dementia, suggesting that delirium pathophysiology involves neuronal injury. Neurofilament light (NFL) is a sensitive biomarker for neuroaxonal injury. Methods: NFL was measured in cerebrospinal fluid (CSF) (n = 130), preoperative serum (n = 192), and postoperative serum (n = 280) in hip fracture patients, and in CSF (n = 123) and preoperative serum (n = 134) in cognitively normal older adults under-going elective surgery. Delirium was diagnosed with the Confusion Assessment Method. Re-sults: Median serum NFL (pg/mL) was elevated in delirium in hip fracture patients (94 vs. 54 pre- and 135 vs. 92 postoperatively, both p < 0.001). Median CSF NFL tended to be higher in hip fracture patients with delirium (1,804 vs. 1,636, p = 0.074). Serum and CSF NFL were posi-tively correlated (ρ = 0.56, p < 0.001). Conclusion: Our findings support an association be-tween neuroaxonal injury and delirium. The correlation between serum and CSF NFL supports the use of NFL as a blood biomarker in future delirium studies.

• Hassel, Bjørnar; Mariussen, Espen; Idland, Ane-Victoria; Dahl, Gry Torsæter; Ræder, Johan & Frihagen, Frede Jon [Vis alle 10 forfattere av denne artikkelen] (2018). CSF sodium at toxic levels precedes delirium in hip fracture patients. Neurotoxicology. ISSN 0161-813X. 69(December), s. 11–16. doi: 10.1016/j.neuro.2018.08.010. Fulltekst i vitenarkiv
• Torbergsen, Anne Cathrine; Watne, Leiv; Frihagen, Frede Jon; Wyller, Torgeir Bruun & Mowe, Morten (2018). Effects of nutritional intervention upon bone turnover in elderly hip fracture patients. Randomized controlled trial. Clinical Nutrition ESPEN. ISSN 2405-4577. doi: 10.1016/j.clnesp.2017.11.012. Fulltekst i vitenarkiv
• Henjum, Kristi; Paulsen, Else Quist; Zetterberg, Henrik; Blennow, Kaj; Nilsson, Lars & Watne, Leiv (2018). CSF sTREM2 in delirium - Relation to Alzheimer's disease CSF biomarkers Abeta42, t-tau and p-tau. Journal of Neuroinflammation. 15(1), s. 1–15. doi: 10.1186/s12974-018-1331-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Delirium and dementia share symptoms of cognitive dysfunctions, and mechanisms of neuroinflammation appear involved in both conditions. Triggering receptor expressed on myeloid cells 2 (TREM2) is linked to dementia and neurodegenerative disease. It encodes expression of an innate immune receptor in the brain expressed by microglia. The level of the soluble fragment of TREM2 (sTREM2) is reported to increase in the cerebrospinal fluid (CSF) already in prodromal and asymptomatic Alzheimer’s disease. Methods We analyzed the level of CSF sTREM2 in relation to delirium and dementia. The study included patients with or without pre-existing dementia who underwent acute hip fracture surgery (n = 120), and some of the patients developed delirium (n = 65). A medical delirium cohort (n = 26) was also examined. ELISA was used to determine the level of sTREM2 in CSF. Results Delirium was associated with a higher level of CSF sTREM2 only among those without pre-existing dementia (p = 0.046, n = 15, n = 44), particularly among patients developing delirium after CSF sampling (p = 0.02, n = 7, n = 44). Between patients with dementia, there was no group difference, but the CSF sTREM2 level increased with waiting time for surgery (rS = 0.39, p = 0.002, n = 60) and correlated well with the CSF Alzheimer’s disease biomarkers, Aβ42, and t-tau/p-tau (rS = 0.40, p = 0.002, rS = 0.46, p < 0.001/ rS = 0.49, p < 0.001, n = 60). Among patients with dementia, the level of Aβ38 and Aβ40 also correlated positively with sTREM2 in CSF (Aβ38MSDrS = 0.44, p = 0.001; Aβ40MSDrS = 0.48, p < 0.001; Aβ42MSDrS = 0.43, p < 0.001, n = 60). Conclusion The findings reinforce the involvement of neuroinflammation in delirium, yet with separate responses in patients with or without pre-existing dementia. Our findings support the concept of primed microglia in neurodegenerative disease and central immune activation after a peripheral trauma in such patients. A CSF biomarker panel of neuroinflammation might be valuable to prevent delirium by identifying patients at risk.

• Guren, Ellen; Figved, Wender; Frihagen, Frede Jon; Watne, Leiv Otto & WESTBERG, MARIANNE (2017). Prosthetic joint infection?a devastating complication of hemiarthroplasty for hip fracture. Acta Orthopaedica. ISSN 1745-3674. 88(4), s. 383–389. doi: 10.1080/17453674.2017.1301009. Fulltekst i vitenarkiv
• Ernst, Gernot Walter; Watne, Leiv Otto; Frihagen, Frede Jon; Wyller, Torgeir Bruun; Dominik, Andreas & Rostrup, Morten (2017). Decreases in heart rate variability are associated with postoperative complications in hip fracture patients. PLOS ONE. 12:e0180423(7), s. 1–14. doi: 10.1371/journal.pone.0180423. Fulltekst i vitenarkiv
• Torbergsen, Anne Cathrine; Watne, Leiv Otto; Wyller, Torgeir Bruun; Frihagen, Frede Jon; Strømsøe, Knut & Bøhmer, Thomas [Vis alle 7 forfattere av denne artikkelen] (2017). Micronutrients and the risk of hip fracture: Case–control study. Clinical Nutrition. ISSN 0261-5614. 36(2), s. 438–443. doi: 10.1016/j.clnu.2015.12.014. Fulltekst i vitenarkiv Vis sammendrag

  Background: Vitamin D, and possibly vitamin K, has an established association to fracture risk. Other vitamins are, however, less studied. Aim: To determine whether specific micronutrients other than 25(OH)D and vitamin K play a role in risk of hip fracture and bone turnover. Methods: In this caseecontrol study, blood was drawn for measurements of vitamins A, B6, B12, C, E, and folic acid as well as the bone turnover markers osteocalcin and bone-specific alkaline phosphatase upon admission for hip fracture in 116 patients and in 73 home-dwelling non fractured controls. Results for vitamin K1 and 25(OH)D from the same populations have been reported previously. Results: Low vitamin A, C, and E concentrations were independently associated with a risk of hip fracture. The adjusted odds ratio (95% confidence interval) per 10 mmol/L increase in vitamin A concentration was 0.74 (0.65e0.84); for 1 mmol/L vitamin C and E: 0.94 (0.92e0.97) and 0.81 (0.74e0.89) respectively. The results were principally unchanged when 25(OH)D, vitamin K1, Body Mass Index, and other potential confounders were adjusted for. All vitamins except B12 and folic acid correlated positively with total osteocalcin and negatively with bone-specific alkaline phosphatase. Conclusions: Low vitamin A, C, and E concentrations are associated with an increased risk of hip fracture, possibly mediated through bone turnover mechanisms. This caseecontrol study is registered at: ClinicalTrials.gov. NCT01738776. The patient related outcome is also registered at: ClinicalTrials.gov. NCT01009268.

• Hov, Karen Roksund; Bolstad, Nils; Idland, Ane-Victoria; Zetterberg, Henrik; Blennow, Kaj & Chaudhry, Farrukh Abbas [Vis alle 10 forfattere av denne artikkelen] (2017). Cerebrospinal Fluid S100B and Alzheimer's Disease Biomarkers in Hip Fracture Patients with Delirium. Dementia and Geriatric Cognitive Disorders Extra. 7(3), s. 374–385. doi: 10.1159/000481853. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. Methods: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method. A consensus-based diagnosis of prefracture dementia was made using all available information. CSF was drawn at the onset of spinal anesthesia. S100B and phosphorylated tau (P-tau) concentrations were measured using electrochemiluminescence immunoassay and enzyme-linked immunosorbent assays, respectively. Results: In the hip fracture population (n = 98) there was no significant difference in CSF S100B concentrations between patients with ongoing preoperative (i.e., prevalent) delirium (n = 36, median [interquartile range] 1.11 μg/L [0.91–1.29]) and patients who never developed delirium (n = 46, 1.08 μg/L [0.92–1.28], p = 0.92). In patients without preoperative delirium, those who developed delirium postoperatively (i.e., incident delirium) (n = 16, 1.38 μg/L [1.08–1.62]) had higher concentrations of S100B than the 46 who never did (p = 0.013). This difference was confined to patients with pathological concentrations of P-tau (≥60 ng/L, n = 38). We also found that P-tau and S100B were correlated in CSF in the elective surgery patients. Conclusions: CSF S100B was elevated in patients with incident delirium who also had pathological levels of the Alzheimer disease biomarker P-tau, suggesting vulnerability caused by a preexisting process of astrocytic activation and tau pathology.

• Llonch, Roser Sala; Idland, Ane-Victoria; Borza, Tom; Watne, Leiv Otto; Wyller, Torgeir Bruun & Brækhus, Anne [Vis alle 10 forfattere av denne artikkelen] (2017). Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with Longitudinal Changes in Cognition. Journal of Alzheimer's Disease. ISSN 1387-2877. 58(3), s. 829–840. doi: 10.3233/JAD-161146. Fulltekst i vitenarkiv Vis sammendrag

  Amyloid deposition occurs in aging, even in individuals free from cognitive symptoms, and is often interpreted as preclinical Alzheimer’s disease (AD) pathophysiology. YKL-40 is a marker of neuroinflammation, being increased in AD, and hypothesized to interact with amyloid-β (Aβ) in causing cognitive decline early in the cascade of AD pathophysiology. Whether and how Aβ and YKL-40 affect brain and cognitive changes in cognitively healthy older adults is still unknown. We studied 89 participants (mean age: 73.1 years) with cerebrospinal fluid samples at baseline, and both MRI and cognitive assessments from two time-points separated by two years. We tested how baseline levels of Aβ42 and YKL-40 correlated with changes in cortical thickness and cognition. Thickness change correlated with Aβ42 only in Aβ42+ participants (<600 pg/mL, n = 27) in the left motor and premotor cortices. Aβ42 was unrelated to cognitive change. Increased YKL-40 was associated with less preservation of scores on the animal naming test in the total sample (r = –0.28, p = 0.012) and less preservation of a score reflecting global cognitive function for Aβ42+ participants (r = –0.58, p = 0.004). Our results suggest a role for inflammation in brain atrophy and cognitive changes in cognitively normal older adults, which partly depended on Aβ accumulation.

• Neerland, Bjørn Erik; Krogseth, Maria; Juliebø, Vibeke; Ranhoff, Anette Hylen; Engedal, Knut & Frihagen, Frede Jon [Vis alle 9 forfattere av denne artikkelen] (2017). Perioperative hemodynamics and risk for delirium and new onset dementia in hip fracture patients; A prospective follow-up study. PLOS ONE. 12(7:e0180641), s. 1–18. doi: 10.1371/journal.pone.0180641. Fulltekst i vitenarkiv Vis sammendrag

  Background Delirium is common in hip fracture patients and many risk factors have been identified. Controversy exists regarding the possible impact of intraoperative control of blood pressure upon acute (delirium) and long term (dementia) cognitive decline. We explored possible associations between perioperative hemodynamic changes, use of vasopressor drugs, risk of delirium and risk of new-onset dementia. Methods: Prospective follow-up study of 696 hip fracture patients, assessed for delirium pre- and postoperatively, using the Confusion Assessment Method. Pre-fracture cognitive function was assessed using the Informant Questionnaire of Cognitive Decline in the Elderly and by consensus diagnosis. The presence of new-onset dementia was determined at follow-up evaluation at six or twelve months after surgery. Blood pressure was recorded at admission, perioperatively and postoperatively. Results: Preoperative delirium was present in 149 of 536 (28%) assessable patients, and 124 of 387 (32%) developed delirium postoperatively (incident delirium). The following risk factors for incident delirium in patients without pre-fracture cognitive impairment were identified: low body mass index, low level of functioning, severity of physical illness, and receipt of ≥ 2 blood transfusions. New-onset dementia was diagnosed at follow-up in 26 of 213 (12%) patients, associated with severity of physical illness, delirium, receipt of vasopressor drugs perioperatively and high mean arterial pressure postoperatively. Conclusion: Risk factors for incident delirium seem to differ according to pre-fracture cognitive status. The use of vasopressors during surgery and/or postoperative hypertension is associated with new-onset dementia after hip fracture.

• Idland, Ane-Victoria; Roser, Sala-Llonch; Borza, Tom; Watne, Leiv Otto; Wyller, Torgeir Bruun & Brækhus, Anne [Vis alle 10 forfattere av denne artikkelen] (2017). CSF neurofilament light levels predict hippocampal atrophy in cognitively healthy older adults. Neurobiology of Aging. ISSN 0197-4580. 49, s. 138–144. doi: 10.1016/j.neurobiolaging.2016.09.012. Fulltekst i vitenarkiv Vis sammendrag

  Cerebrospinal fluid (CSF) neurofilament light (NFL) is a marker of axonal degeneration. We tested whether CSF NFL levels predict hippocampal atrophy rate in cognitively healthy older adults independently of the established CSF Alzheimer's disease (AD) biomarkers, β-amyloid 1-42, and phosphorylated tau (P-tau). We included 144 participants in a 2-year longitudinal study with baseline CSF measures and 2 magnetic resonance images. Eighty-eight participants had full data available. A subgroup of 36 participants with very low AD risk was also studied. NFL predicted hippocampal atrophy rate independently of age, β-amyloid 1-42, and P-tau. Including NFL, P-tau, and age in the same model, higher NFL and lower P-tau predicted higher hippocampal atrophy (R2 = 0.20, NFL: β = -0.34; p = 0.003; P-tau: β = 0.27; p = 0.009). The results were upheld in the participants with very low AD risk. NFL predicted neurodegeneration in older adults with very low AD probability. We suggest that factors previously shown to be important for brain degeneration in mild cognitive impairment may also impact changes in normal aging, demonstrating that NFL is likely to indicate AD-independent, age-expected neurodegeneration.

• Fjell, Anders Martin; Idland, Ane-Victoria; Llonch, Roser Sala; Watne, Leiv Otto; Borza, Tom & Brækhus, Anne [Vis alle 11 forfattere av denne artikkelen] (2017). Neuroinflammation and tau interact with amyloid in predicting sleep problems in aging independently of atrophy. Cerebral Cortex. ISSN 1047-3211. 28(8), s. 2775–2785. doi: 10.1093/cercor/bhx157. Fulltekst i vitenarkiv
• Idland, Ane-Victoria; Wyller, Torgeir Bruun; Støen, Randi; Dahl, Gry Torsæter; Frihagen, Frede Jon & Brækhus, Anne [Vis alle 8 forfattere av denne artikkelen] (2017). Cerebrospinal Fluid Phosphate in Delirium after Hip Fracture. Dementia and Geriatric Cognitive Disorders Extra. doi: 10.1159/000478723. Fulltekst i vitenarkiv Vis sammendrag

  Aims: Phosphate is essential for neuronal activity. We aimed to investigate whether delirium is associated with altered phosphate concentrations in cerebrospinal fluid (CSF) and serum. Methods: Seventy-seven patients with hip fracture were assessed for delirium before and after acute surgery. Prefracture dementia was diagnosed by an expert panel. Phosphate was measured in CSF obtained immediately before spinal anesthesia (n = 77) and in serum (n = 47). CSF from 23 cognitively healthy elderly patients undergoing spinal anesthesia was also analyzed. Results: Hip fracture patients with prevalent delirium had higher CSF phosphate concentrations than those without delirium (median 0.63 vs. 0.55 mmol/L, p = 0.001). In analyses stratified on dementia status, this difference was only significant in patients with dementia. Serum phosphate was ∼1 mmol/L; there was no association between serum phosphate concentration and delirium status. CSF phosphate did not correlate with serum levels. Conclusion: Patients with delirium superimposed on dementia have elevated phosphate levels.

• Hall, Roanna J.; Watne, Leiv Otto; Idland, Ane-Victoria; Ræder, Johan; Frihagen, Frede Jon & MacLullich, Alasdair M.J. [Vis alle 9 forfattere av denne artikkelen] (2016). Cerebrospinal fluid levels of neopterin are elevated in delirium after hip fracture. Journal of Neuroinflammation. 13:170. doi: 10.1186/s12974-016-0636-1. Fulltekst i vitenarkiv Vis sammendrag

  Background The inflammatory cell product neopterin is elevated in serum before and during delirium. This suggests a role for disordered cell-mediated immunity or oxidative stress. Cerebrospinal fluid (CSF) neopterin levels reflect brain neopterin levels more closely than serum levels. Here we hypothesized that CSF neopterin levels would be higher in delirium. Methods In this prospective cohort study, 139 elderly patients with acute hip fracture were recruited in Oslo and Edinburgh. Delirium was diagnosed with the confusion assessment method performed daily pre-operatively and on the first 5 days post-operatively. Paired CSF and blood samples were collected at the onset of spinal anaesthesia. Neopterin levels were measured using high-performance liquid chromatography. Results Sixty-four (46 %) of 139 hip fracture patients developed delirium perioperatively. CSF neopterin levels were higher in delirium compared to controls (median 29.6 vs 24.7 nmol/mL, p = 0.003), with highest levels in patients who developed delirium post-operatively. Serum neopterin levels were also higher in delirium (median 37.0 vs 27.1 nmol/mL, p = 0.003). CSF neopterin remained significantly associated with delirium after controlling for relevant risk factors. Higher neopterin levels were associated with poorer outcomes (death or new institutionalization) 1 year after surgery (p = 0.02 for CSF and p = 0.03 for serum). Conclusions This study is the first to examine neopterin in CSF from patients with delirium. Our findings suggest potential roles for activation of cell-mediated immune responses or oxidative stress in the delirium process. High levels of serum or CSF neopterin in hip fracture patients may also be useful in predicting poor outcomes.

• Krogseth, Maria; Watne, Leiv Otto; Juliebø, Vibeke; Skovlund, Eva; Engedal, Knut & Frihagen, Frede Jon [Vis alle 7 forfattere av denne artikkelen] (2016). Delirium is a risk factor for further cognitive decline in cognitively impaired hip fracture patients. Archives of Gerontology and Geriatrics. ISSN 0167-4943. 64, s. 38–44. doi: 10.1016/j.archger.2015.12.004. Fulltekst i vitenarkiv
• Neerland, Bjørn Erik; Hall, Roanna J.; Seljeflot, Ingebjørg; Frihagen, Frede Jon; MacLullich, Alasdair M.J. & Ræder, Johan [Vis alle 8 forfattere av denne artikkelen] (2016). Associations between delirium and preoperative cerebrospinal fluid C-reactive protein, interleukin-6, and interleukin-6 receptor in individuals with acute hip fracture. Journal of The American Geriatrics Society. ISSN 0002-8614. 64(7), s. 1456–1463. doi: 10.1111/jgs.14238. Fulltekst i vitenarkiv
• Hov, Karen Roksund; Berg, Jens Petter; Frihagen, Frede Jon; Ræder, Johan; Hall, Roanna J. & Wyller, Torgeir Bruun [Vis alle 7 forfattere av denne artikkelen] (2016). Blood-cerebrospinal fluid barrier integrity in delirium determined by Q-Albumin. Dementia and Geriatric Cognitive Disorders. ISSN 1420-8008. 41(3-4), s. 192–198. doi: 10.1159/000443789. Fulltekst i vitenarkiv
• Idland, Ane-Victoria; Wyller, Torgeir Bruun; Støen, Randi; Eri, Lars Magne; Frihagen, Frede Jon & Ræder, Johan [Vis alle 13 forfattere av denne artikkelen] (2016). Preclinical amyloid-β and axonal degeneration pathology in delirium. Journal of Alzheimer's Disease. ISSN 1387-2877. 55(1), s. 371–379. doi: 10.3233/JAD-160461. Fulltekst i vitenarkiv
• Berg, Geir Vegard; Watne, Leiv Otto & Gjevjon, Edith L Roth (2016). Ny screening gir sikrere diagnose - Bruk av screeninginstrumentet 4AT kan forbedre diagnostiseringen av akutt delirium. Tidsskriftet sykepleien. ISSN 0806-7511. 104(3), s. 52–53. doi: 10.4220/Sykepleiens.2016.56686. Fulltekst i vitenarkiv
• Watne, Leiv Otto; Idland, Ane-Victoria; Fekkes, Durk; Ræder, Johan; Frihagen, Frede Jon & Ranhoff, Anette Hylen [Vis alle 10 forfattere av denne artikkelen] (2016). Increased CSF levels of aromatic amino acids in hip fracture patients with delirium suggests higher monoaminergic activity. BMC Geriatrics. doi: 10.1186/s12877-016-0324-0. Fulltekst i vitenarkiv Vis sammendrag

  Background To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and/or monoamine metabolites in cerebrospinal fluid (CSF) and serum.Methods In this prospective cohort study, 77 patients admitted with an acute hip fracture to Oslo University Hospital, Norway, were studied. The concentrations of amino acids in CSF and serum were determined by high performance liquid chromatography. The patients were assessed daily for delirium by the Confusion Assessment Method (pre-operatively and post-operative day 1–5 (all) or until discharge (delirious patients)). Pre-fracture dementia status was decided by an expert panel. Serum was collected pre-operatively and CSF immediately before spinal anesthesia.Results Fifty-three (71 %) hip fracture patients developed delirium. In hip fracture patients without dementia (n = 39), those with delirium had significantly higher CSF levels of tryptophan (40 % higher), tyrosine (60 % higher), phenylalanine (59 % higher) and the monoamine metabolite 5-hydroxyindoleacetate (23 % higher) compared to those without delirium. The same amino acids were also higher in CSF in delirious patients with dementia (n = 38). The correlations between serum and CSF amino acid levels were poor.Conclusion Higher CSF levels of monoamine precursors in hip fracture patients with delirium suggest a higher monoaminergic activity in the central nervous system during delirium in this patient group.

• O'Sullivan, Roisin; Meagher, David; Leonard, Maeve; Watne, Leiv Otto; Hall, Roanna J. & MacLullich, Alasdair M.J. [Vis alle 8 forfattere av denne artikkelen] (2015). A comparison of the revised Delirium Rating Scale (DRS-R98) and the Memorial Delirium Assessment Scale (MDAS) in a palliative care cohort with DSM-IV delirium. Palliative & Supportive Care. ISSN 1478-9515. 13(4), s. 937–944. doi: 10.1017/S1478951514000613. Fulltekst i vitenarkiv
• Torbergsen, Anne Cathrine; Watne, Leiv Otto; Wyller, Torgeir Bruun; Frihagen, Frede Jon; Strømsøe, Knut & Bøhmer, Thomas [Vis alle 7 forfattere av denne artikkelen] (2015). Vitamin K1 and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: A case control study. Clinical Nutrition. ISSN 0261-5614. 34(1), s. 101–106. doi: 10.1016/j.clnu.2014.01.016. Fulltekst i vitenarkiv
• Torbergsen, Anne Cathrine; Watne, Leiv Otto; Frihagen, Frede Jon; Wyller, Torgeir Bruun; Brugård, Anniken & Mowe, Morten (2015). Vitamin deficiency as a risk factor for delirium. European Geriatric Medicine. ISSN 1878-7649. 6(4), s. 314–318. doi: 10.1016/j.eurger.2014.09.002. Fulltekst i vitenarkiv

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• Marshall, Timothy J.; Watne, Leiv & Sanders, Robert D. (2025). Mechanisms of perioperative neuronal injury and the search for therapies. British Journal of Anaesthesia. ISSN 0007-0912. doi: 10.1016/j.bja.2024.12.032. Fulltekst i vitenarkiv
• Wang, Heling; Siow, Richard; Schmauck-Medina, Tomás Alejandro; Zhang, Jianying; Sandset, Per Morten & Filshie, Clare [Vis alle 38 forfattere av denne artikkelen] (2024). Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia: Recent Progress on the Mechanisms and Interventional Strategies. The journals of gerontology. Series A, Biological sciences and medical sciences. ISSN 1079-5006. 79(4), s. 1–10. doi: 10.1093/gerona/glae029. Fulltekst i vitenarkiv Vis sammendrag

  Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a “Money Follows Cooperation agreement” between the 2 nations. The inaugural Norway–UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.

• Sanders, Robert D.; Watne, Leiv; Roberson, Shawniqua Williams; Kimchi, Eyal Y.; Slooter, Arjen J.C. & Cunningham, Colm [Vis alle 10 forfattere av denne artikkelen] (2024). International Delirium Pathophysiology & Electrophysiology Network for Data sharing (iDEPEND). BJA Open. 11. doi: 10.1016/j.bjao.2024.100304. Fulltekst i vitenarkiv
• Hella, Mathias Nikolai Petersen; Sønnesyn, Hogne; Bergland, Anne Katrine; Aarsland, Dag; Djuv, Ane & Vik-Mo, Audun Osland [Vis alle 10 forfattere av denne artikkelen] (2023). Vi må bry oss om delirium. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(5). doi: 10.4045/tidsskr.23.0037. Fulltekst i vitenarkiv
• Hella, Mathias Nikolai Petersen; Bergland, Anne Katrine; Soennesyn, Hogne; Halaas, Nathalie Bodd; Watne, Leiv & Bonanni, Laura [Vis alle 7 forfattere av denne artikkelen] (2023). What we know about the possible link between delirium and dementia with Lewy bodies, and why we need to learn more. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 147(5), s. 401–402. doi: 10.1111/acps.13526. Fulltekst i vitenarkiv
• Aman, Yahyah; Ryan, B; Torsetnes, Silje Bøen; Knapskog, Anne Brita; Watne, Leiv & McEwan, W [Vis alle 7 forfattere av denne artikkelen] (2020). Enhancing mitophagy as a therapeutic approach for neurodegenerative diseases. International review of neurobiology. ISSN 0074-7742. 155. doi: 10.1016/bs.irn.2020.02.008. Fulltekst i vitenarkiv
• Myrstad, Marius; Neerland, Bjørn Erik; Hagberg, Guri & Watne, Leiv Otto (2017). Vurdering av mental status hos akutt syke gamle. 137(12), s. 1–2. doi: 10.4045/tidsskr.17.0480. Fulltekst i vitenarkiv
• Tieges, Zoe; Watne, Leiv Otto; Bing-Jonsson, Pia Cecilie; Stíobhairt, A & MacLullich, Alasdair M.J. (2017). Diversity of opinions on delirium severity: an international survey of 344 delirium specialists. Fulltekst i vitenarkiv Vis sammendrag

  Background Severity grading has potential use in delirium research, as predictor of outcomes, and for monitoring delirium course. However, there is uncertainty regarding its definition, measurement and applicability. An international survey of delirium specialists was undertaken to evaluate current opinions on delirium severity. Methods An online survey was distributed among members of three international delirium associations and other interested parties. The survey covered severity markers, prognostic symptoms, delirium with and without dementia, and assessment tools. Consensus was defined as ≥75% agreement. Results Three hundred forty-four eligible respondents completed the survey (completion rate 74%). Respondents were from the UK (32%), US (23%), Australia (18%) and 24 other countries. Most were doctors (59%) and nurses (30%) working in geriatrics (38%), ICUs (23%) and assessment units (22%). Experts agreed that poor outcomes (84%), symptom intensity (81%), patient safety (79%), delirium duration (77%) and distress (77%) were important markers of severity. The number of symptoms was not considered important (51%). Respondents identified multiple symptoms that could predict poor prognosis, but there was consensus only on "altered arousal" (83%). Symptoms thought to be present in severe delirium included inattention (94%), disorientation (88%) and sleep disturbance (87%). About half of respondents (47%) stated that delirium symptom profiles differ between those with and without dementia. Severity assessment tools were considered useful in research (18%), clinical practice (22%) or both (33%), but 46% of respondents had never used one. The Confusion Assessment Method-Severity scale and the Delirium Rating Scale Revised-98 were most commonly used. Conclusion This survey demonstrates diverse opinions on delirium severity among specialists. The view that the number of symptoms does not indicate severity contrasts with current practice. Further, current tools mostly do not include level of arousal. This study challenges current conceptualisations of the multi-dimensional construct of delirium severity, and highlights the need for development of weighted scoring tools.

• Wyller, Torgeir Bruun & Watne, Leiv Otto (2016). Re: En kvinne i 70-årene med rask forverring av kognitiv funksjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(16), s. 1325–1325. doi: 10.4045/tidsskr.16.0686. Fulltekst i vitenarkiv
• Johnsen, Lars Gunnar; Watne, Leiv Otto; Frihagen, Frede Jon; Helbostad, Jorunn L.; Prestmo, Anders & Saltvedt, Ingvild [Vis alle 8 forfattere av denne artikkelen] (2015). Hvorfor ortogeriatri? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 135(6), s. 523–524. doi: 10.4045/tidsskr.15.0188. Fulltekst i vitenarkiv

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