Tormod Fladby

• Padrela, Beatriz; Mahroo, Amnah; Tee, Mervin; Sneve, Markus Handal; Moyaert, Paulien & Geier, Oliver [Vis alle 43 forfattere av denne artikkelen] (2024). Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol. BMJ Open. ISSN 2044-6055. 14(3). doi: 10.1136/bmjopen-2023-081635.
• Mehdipour Ghazi, Mostafa; Selnes, Per; Timón-Reina, Santiago; Tecelão, Sandra; Ingala, Silvia & Bjørnerud, Atle [Vis alle 9 forfattere av denne artikkelen] (2024). Comparative analysis of multimodal biomarkers for amyloid-beta positivity detection in Alzheimer's disease cohorts. Frontiers in Aging Neuroscience. ISSN 1663-4365. 16. doi: 10.3389/fnagi.2024.1345417.
• Wang, He-Ling; Siow, Richard; Schmauck-Medina, Tomas; 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). doi: 10.1093/gerona/glae029.
• Hemminghyth, Mathilde Suhr; Chwiszczuk, Luiza; Breitve, Monica Haraldseid; Gisladottir, Berglind; Grøntvedt, Gøril Rolfseng & Nakling, Arne Exner [Vis alle 9 forfattere av denne artikkelen] (2023). Cerebrospinal fluid neurofilament light chain mediates age-associated lower learning and memory in healthy adults. Neurobiology of Aging. ISSN 0197-4580. 135, s. 39–47. doi: 10.1016/j.neurobiolaging.2023.12.005. Fulltekst i vitenarkiv
• Nordengen, Kaja; Kirsebom, Bjørn-Eivind Seljelid; Richter, Grit; Pålhaugen, Lene; Gisladottir, Berglind & Siafarikas, Nikias Ioannis [Vis alle 22 forfattere av denne artikkelen] (2023). Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer’s disease. Journal of Neuroinflammation. ISSN 1742-2094. 20(1). doi: 10.1186/s12974-023-02973-w. Fulltekst i vitenarkiv
• Aspli, Klaus Thanke; Aaseth, Jan; Holmøy, Trygve; Blennow, Kaj; Zetterberg, Henrik & Kirsebom, Bjørn-Eivind Seljelid [Vis alle 8 forfattere av denne artikkelen] (2023). CSF, Blood, and MRI Biomarkers in Skogholt’s Disease—A Rare Neurodegenerative Disease in a Norwegian Kindred. Brain Sciences. ISSN 2076-3425. 13(11). doi: 10.3390/brainsci13111511. Fulltekst i vitenarkiv
• Espenes, Johan Jacob; Lorentzen, Ingrid Myrvoll; Eliassen, Ingvild Vøllo; Hessen, Erik; Waterloo, Knut K & Timón, Santiago [Vis alle 10 forfattere av denne artikkelen] (2023). Regression-based normative data for the D-KEFS Color-Word Interference Test in Norwegian adults ages 20–85. The Clinical Neuropsychologist. ISSN 1385-4046. doi: 10.1080/13854046.2023.2276967. Fulltekst i vitenarkiv
• Öhman, Fredrik; Eckerström, Marie; Hessen, Erik; Espenes, Johan Jacob; Eliassen, Ingvild Vøllo & Lorentzen, Ingrid Myrvoll [Vis alle 12 forfattere av denne artikkelen] (2023). Demographically adjusted Rey–Osterrieth Complex Figure Test norms in a Swedish and Norwegian cohort aged 49–77 years and comparison with North American norms. Scandinavian Journal of Psychology. ISSN 0036-5564. doi: 10.1111/sjop.12966. Fulltekst i vitenarkiv
• Timón, Santiago; Rincón, Mariano; Martínez-Tomás, Rafael; Kirsebom, Bjørn-Eivind Seljelid & Fladby, Tormod (2023). A Knowledge Graph Framework for Dementia Research Data. Applied Sciences. ISSN 2076-3417. 13(18), s. 1–23. doi: 10.3390/app131810497. Fulltekst i vitenarkiv
• Røvang, Martin Soria; Selnes, Per; MacIntosh, Bradley; Groote, Inge Rasmus; Pålhaugen, Lene & Sudre, Carole H [Vis alle 8 forfattere av denne artikkelen] (2023). Segmenting white matter hyperintensities on isotropic three-dimensional Fluid Attenuated Inversion Recovery magnetic resonance images: Assessing deep learning tools on a Norwegian imaging database. PLOS ONE. ISSN 1932-6203. 18(8). doi: 10.1371/journal.pone.0285683. Vis sammendrag

  An important step in the analysis of magnetic resonance imaging (MRI) data for neuroimaging is the automated segmentation of white matter hyperintensities (WMHs). Fluid Attenuated Inversion Recovery (FLAIR-weighted) is an MRI contrast that is particularly useful to visualize and quantify WMHs, a hallmark of cerebral small vessel disease and Alzheimer’s disease (AD). In order to achieve high spatial resolution in each of the three voxel dimensions, clinical MRI protocols are evolving to a three-dimensional (3D) FLAIR-weighted acquisition. The current study details the deployment of deep learning tools to enable automated WMH segmentation and characterization from 3D FLAIR-weighted images acquired as part of a national AD imaging initiative. Based on data from the ongoing Norwegian Disease Dementia Initiation (DDI) multicenter study, two 3D models—one off-the-shelf from the NVIDIA nnU-Net framework and the other internally developed—were trained, validated, and tested. A third cutting-edge Deep Bayesian network model (HyperMapp3r) was implemented without any de-novo tuning to serve as a comparison architecture. The 2.5D in-house developed and 3D nnU-Net models were trained and validated in-house across five national collection sites among 441 participants from the DDI study, of whom 194 were men and whose average age was (64.91 +/- 9.32) years. Both an external dataset with 29 cases from a global collaborator and a held-out subset of the internal data from the 441 participants were used to test all three models. These test sets were evaluated independently. The ground truth human-in-the-loop segmentation was compared against five established WMH performance metrics. The 3D nnU-Net had the highest performance out of the three tested networks, outperforming both the internally developed 2.5D model and the SOTA Deep Bayesian network with an average dice similarity coefficient score of 0.76 +/- 0.16. Our findings demonstrate that WMH segmentation models can achieve high performance when trained exclusively on FLAIR input volumes that are 3D volumetric acquisitions. Single image input models are desirable for ease of deployment, as reflected in the current embedded clinical research project. The 3D nnU-Net had the highest performance, which suggests a way forward for our need to automate WMH segmentation while also evaluating performance metrics during on-going data collection and model retraining.

• Lorentzen, Ingrid Myrvoll; Espenes, Johan Jacob; Eliassen, Ingvild Vøllo; Hessen, Erik; Waterloo, Knut K & Nakling, Arne Exner [Vis alle 10 forfattere av denne artikkelen] (2023). Investigating the relationship between allocentric spatial working memory and biomarker status in preclinical and prodromal Alzheimer’s disease. Applied neuropsychology: Adult. ISSN 2327-9095. doi: 10.1080/23279095.2023.2236262. Fulltekst i vitenarkiv
• Jarholm, Jonas Alexander; Bjørnerud, Atle; Dalaker, Turi Olene; Sadat Akhavi, Mehdi; Kirsebom, Bjørn-Eivind & Pålhaugen, Lene [Vis alle 14 forfattere av denne artikkelen] (2023). Medial Temporal Lobe Atrophy in Predementia Alzheimer's Disease: A Longitudinal Multi-Site Study Comparing Staging and A/T/N in a Clinical Research Cohort. Journal of Alzheimer's Disease. ISSN 1387-2877. 94(1), s. 259–279. doi: 10.3233/JAD-221274. Fulltekst i vitenarkiv
• Waggestad, Therese Händel; Kirsebom, Bjørn-Eivind; Strobel, Carsten; Wallin, Anders; Eckerström, Marie & Fladby, Tormod [Vis alle 7 forfattere av denne artikkelen] (2023). Improving validity of the trail making test with alphabet support. Frontiers in Psychology. ISSN 1664-1078. 14. doi: 10.3389/fpsyg.2023.1227578. Fulltekst i vitenarkiv Vis sammendrag

  Objective: The Trail Making Test (TMT) is commonly used worldwide to evaluate cognitive decline and car driving ability. However, it has received critique for its dependence on the Latin alphabet and thus, the risk of misclassifying some participants. Alphabet support potentially increases test validity by avoiding misclassification of executive dysfunction in participants with dyslexia and those with insufficient automatization of the Latin alphabet. However, Alphabet support might render the test less sensitive to set-shifting, thus compromising the validity of the test. This study compares two versions of the TMT: with and without alphabet support. Methods: We compared the TMT-A, TMT-B, and TMT-B:A ratios in two independent normative samples with (n = 220) and without (n = 64) alphabet support using multiple regression analysis adjusted for age and education. The sample comprised Scandinavians aged 70–84 years. Alphabet support was included by adding the Latin alphabet A–L on top of the page on the TMT-B. We hypothesized that alphabet support would not change the TMT-B:A ratio. Results: After adjusting for age and years of education, there were no significant differences between the two samples in the TMT-A, TMT-B, or the ratio score (TMT-B:A). Conclusion: Our results suggest that the inclusion of alphabet support does not alter TMT’s ability to measure set-shifting in a sample of older Scandinavian adults.

• Kirsebom, Bjørn-Eivind; Richter, Grit; Nordengen, Kaja; Aarsland, Dag; Bråthen, Geir & Tijms, Betty M [Vis alle 15 forfattere av denne artikkelen] (2022). Stable cerebrospinal fluid neurogranin and β-site amyloid precursor protein cleaving enzyme 1 levels differentiate predementia Alzheimer's disease patients. Brain Communications. ISSN 2632-1297. 4(5), s. 1–16. doi: 10.1093/braincomms/fcac244. Fulltekst i vitenarkiv Vis sammendrag

  Cerebrospinal fluid (CSF) β-site amyloid precursor protein cleaving enzyme 1 (BACE1), neurogranin and the neurogranin/BACE1 ratio are proposed markers for Alzheimer’s disease. BACE1 is also a drug target. However, CSF levels may differ between early-stage amyloid plaque formation (A) and later stage downstream tau-tangle pathology (T) and neurodegeneration (N) and may be expressed as an A/T/N stage (e.g. A+/T−/N or A+/T+/N+). Whether BACE1 and neurogranin levels are persistent traits or change with disease progression is unknown. The aim of this study was to investigate whether CSF neurogranin and BACE1 concentrations differ between A/T/N stages, whether these change over time and correlate with memory decline. This may have implications for patient selection in future trials. We used CSF markers to determine A/T/N stage using amyloid beta42/40 ratio, p-tau181 and total-tau respectively in predementia Alzheimer’s disease cases (n = 176) [including cases that progressed to dementia (n = 10)] and controls (n = 74) from the Norwegian Dementia Disease Initiation cohort. We selected cases at the presumed early (A+/T−/N−, n = 86) and late stages (A+/T+/N+, n = 90) of the Alzheimer’s disease continuum and controlled with normal markers (A−/T−/N−, n = 74). A subset of subjects in all A/T/N groups underwent repeat CSF sampling at approximately 2-year intervals up to 6 years from baseline. Using linear mixed models, longitudinal measurements of CSF BACE1 and neurogranin levels in A+/T−/N− and A+/T+/N+ as compared to A−/T−/N− healthy controls were performed. Next, we measured changes in CSF BACE1 and neurogranin levels in cases that progressed from A−/T−/N− to A+/T−/N− (n = 12), from A+/T−/N− to A+/T or N+ (n = 12), remained stable A+/T−/N− (n = 26), remained stable A+/T+/N+ (n = 28) compared with controls remaining stable A−/T−/N− (n = 33). Lastly, associations between these markers and memory decline were assessed. Compared with A−/T−/N− healthy controls, neurogranin was unaltered in A+/T−/N− (n.s.) but higher in A+/T+/N+ (P < 0.0001). In contrast, BACE1 was lower in A+/T−/N− (P < 0.05) and higher in A+/T+/N+ (P < 0.0001). The neurogranin/BACE1 ratio was increased in both A+/T−/N− (P < 0.05) and A+/T+/N+ (P < 0.0001) groups as compared to A-/T-/N- healthy controls and was more strongly associated with memory decline (b = −0.29, P = 0.0006) than neurogranin (b = −0.20, P = 0.002) and BACE1 (b = −0.13, P = 0.046). Neurogranin and BACE1 level differences remained stable over time not only within A/T/N groups but also in patients progressing to more pathological A/T/N stages (e.g. progressing from A+/T−/N− to A + T or N+) and in cases progressing to dementia. Our results suggest that neurogranin and BACE1 levels may differentiate pathomechanistic Alzheimer’s disease subgroups, putatively with different options for treatment.

• Nordengen, Kaja; Pålhaugen, Lene; Bettella, Francesco; Bahrami, Shahram; Selnes, Per & Jarholm, Jonas Alexander [Vis alle 10 forfattere av denne artikkelen] (2022). Phenotype-informed polygenic risk scores are associated with worse outcome in individuals at risk of Alzheimer's disease. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. ISSN 2352-8729. 14(1), s. 1–13. doi: 10.1002/dad2.12350. Fulltekst i vitenarkiv
• Aarsland, Dag; Khalifa, Khadija; Bergland, Anne Katrine; Sønnesyn, Hogne; Oppedal, Ketil & Holteng, Lise Birgitte Austbø [Vis alle 14 forfattere av denne artikkelen] (2022). A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia. The American journal of geriatric psychiatry. ISSN 1064-7481. 31(2), s. 141–151. doi: 10.1016/j.jagp.2022.10.002. Fulltekst i vitenarkiv
• Grøntvedt, Gøril Rolfseng; Sando, Sigrid Botne; Lauridsen, Camilla; Bråthen, Geir; White, Linda Rosemary & Salvesen, Øyvind [Vis alle 11 forfattere av denne artikkelen] (2022). Association of Klotho protein levels and KL-VS heterozygosity with Alzheimer disease and amyloid and tau burden. JAMA Network Open. ISSN 2574-3805. 5(11), s. 1–13. doi: 10.1001/jamanetworkopen.2022.43232. Fulltekst i vitenarkiv
• Eliassen, Ingvild Vøllo; Kirsebom, Bjørn-Eivind; Fladby, Tormod; Waterloo, Knut; Sando, Sigrid Botne & Hemminghyth, Mathilde Suhr [Vis alle 12 forfattere av denne artikkelen] (2022). Regression-Based Cognitive Change Norms Applied in Biochemically Defined Predementia Alzheimer’s Disease. Neuropsychology. ISSN 0894-4105. 37(1), s. 32–43. doi: 10.1037/neu0000853. Fulltekst i vitenarkiv Vis sammendrag

  Objective: We aim to develop 2-year cognitive change norms for adults ages 41–84 for six cognitive tests, and to evaluate these norms in groups with AD biomarkers. Background: Practice effects are common in repeated neuropsychological testing. Not accounting for practice effects may obscure cognitive decline in early Alzheimer’s disease (AD). Method: We developed standardized regression-based change norms from normative samples consisting of healthy controls from the Dementia Disease Initiation study (n = 125), the Trønderbrain study (n = 57), and the Gothenburg mild cognitive impairment (MCI) study (n = 65). Norms were applied in a sample with cognitive symptoms (subjective cognitive decline or MCI) and AD cerebrospinal fluid (CSF) biomarkers (n = 246), classified according to the A/T/N system. Results: The change norms adjusted for pertinent demographics and practice effects. The group with cognitive complaints displayed a trend toward cognitive decline compared to the normative group, with the A+T/N+ subgroup showing the most marked decline. This was observed in tests of episodic memory and cognitive flexibility/divided attention. Conclusions: We present 2-year cognitive change norms for adults between 41 and 84 years, adjusted for practice and demographics. A web-based change norm calculator is provided.

• Jansen, Iris E.; van der Lee, Sven J.; Gomez-Fonseca, Duber; de Rojas, Itziar; Dalmasso, Maria Carolina & Grenier-Boley, Benjamin [Vis alle 50 forfattere av denne artikkelen] (2022). Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers. Acta Neuropathologica. ISSN 0001-6322. 144(5), s. 821–842. doi: 10.1007/s00401-022-02454-z. Fulltekst i vitenarkiv Vis sammendrag

  Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.

• Espenes, Jacob; Eliassen, Ingvild Vøllo; Öhman, Fredrik; Hessen, Erik; Waterloo, Knut K & Eckerström, Marie [Vis alle 13 forfattere av denne artikkelen] (2022). Regression‐based normative data for the Rey Auditory Verbal Learning Test in Norwegian and Swedish adults aged 49–79 and comparison with published norms. The Clinical Neuropsychologist. ISSN 1385-4046. doi: 10.1080/13854046.2022.2106890. Fulltekst i vitenarkiv
• Motazedi, Ehsan; Cheng, Weiqiu; Thomassen, Jesper Qvist; Frei, Oleksandr; Rongve, Arvid & Athanasiu, Lavinia [Vis alle 30 forfattere av denne artikkelen] (2022). Using Polygenic Hazard Scores to Predict Age at Onset of Alzheimer's Disease in Nordic Populations. Journal of Alzheimer's Disease. ISSN 1387-2877. 88(4), s. 1533–1544. doi: 10.3233/JAD-220174. Vis sammendrag

  Background: Polygenic hazard scores (PHS) estimate age-dependent genetic risk of late-onset Alzheimer’s disease (AD), but there is limited information about the performance of PHS on real-world data where the population of interest differs from the model development population and part of the model genotypes are missing or need to be imputed. Objective: The aim of this study was to estimate age-dependent risk of late-onset AD using polygenic predictors in Nordic populations. Methods: We used Desikan PHS model, based on Cox proportional hazards assumption, to obtain age-dependent hazard scores for AD from individual genotypes in the Norwegian DemGene cohort (n = 2,772). We assessed the risk discrimination and calibration of Desikan model and extended it by adding new genotype markers (the Desikan Nordic model). Finally, we evaluated both Desikan and Desikan Nordic models in two independent Danish cohorts: The Copenhagen City Heart Study (CCHS) cohort (n = 7,643) and The Copenhagen General Population Study (CGPS) cohort (n = 10,886). Results: We showed a robust prediction efficiency of Desikan model in stratifying AD risk groups in Nordic populations, even when some of the model SNPs were missing or imputed. We attempted to improve Desikan PHS model by adding new SNPs to it, but we still achieved similar risk discrimination and calibration with the extended model. Conclusion: PHS modeling has the potential to guide the timing of treatment initiation based on individual risk profiles and can help enrich clinical trials with people at high risk to AD in Nordic populations.

• Borda, Miguel Germán; Ferreira, Daniel; Selnes, Per; Tovar-Rios, Diego Alejandro; Jaramillo-Jiménez, Alberto & Kirsebom, Bjørn-Eivind [Vis alle 12 forfattere av denne artikkelen] (2022). Timed Up and Go in People with Subjective Cognitive Decline Is Associated with Faster Cognitive Deterioration and Cortical Thickness. Dementia and Geriatric Cognitive Disorders. ISSN 1420-8008. 51(1), s. 63–72. doi: 10.1159/000522094. Fulltekst i vitenarkiv
• Jansen, Willemijn J.; Janssen, Olin; Tijms, Betty M.; Vos, Stephanie J. B.; Ossenkoppele, Rik & Visser, Pieter Jelle [Vis alle 182 forfattere av denne artikkelen] (2022). Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum. JAMA Neurology. ISSN 2168-6149. 79(3), s. 228–243. doi: 10.1001/jamaneurol.2021.5216. Vis sammendrag

  Importance One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design. Objective To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates. Design, Setting, and Participants This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria. Exposures Alzheimer disease biomarkers detected on PET or in CSF. Main Outcomes and Measures Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations. Results Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling–based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, −2% to 9%; P = .18). Conclusions and Relevance This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.

• Bellenguez, Céline; Küçükali, Fahri; Jansen, Iris E.; Kleineidam, Luca; Moreno-Grau, Sonia & Amin, Najaf [Vis alle 407 forfattere av denne artikkelen] (2022). New insights into the genetic etiology of Alzheimer's disease and related dementias. Nature Genetics. ISSN 1061-4036. 54(4), s. 412–436. doi: 10.1038/s41588-022-01024-z. Fulltekst i vitenarkiv Vis sammendrag

  Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

• Grambaite, Ramune; Arnesen, Marie; Hjemdal, Odin; Fladby, Tormod & Thommessen, Bente (2022). Hukommelse etter iskemisk hjerneslag. Nevropsykologi : Medlemsblad for Norsk Nevropsykologisk Forening. ISSN 1500-8347. 24(1), s. 4–11. Fulltekst i vitenarkiv
• Janssen, Olin; Jansen, Willemijn J.; Vos, Stephanie J.B.; Boada, Mercè; Parnetti, Lucilla & Gabryelewicz, Tomasz [Vis alle 61 forfattere av denne artikkelen] (2021). Characteristics of subjective cognitive decline associated with amyloid positivity. Alzheimer's & Dementia. ISSN 1552-5260. doi: 10.1002/alz.12512.
• Siafarikas, Nikias Ioannis; Kirsebom, Bjørn-Eivind; Srivastava, Deepak P; Eriksson, Cecilia Magdalena; Auning, Eirik & Hessen, Erik [Vis alle 10 forfattere av denne artikkelen] (2021). Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression. Scientific Reports. ISSN 2045-2322. 11. doi: 10.1038/s41598-021-99794-9. Fulltekst i vitenarkiv Vis sammendrag

  To explore markers for synaptic function and Alzheimer disease (AD) pathology in late life depression (LLD), predementia AD and normal controls (NC). A cross-sectional study to compare cerebrospinal fluid (CSF) levels of neurogranin (Ng), Beta-site amyloid-precursor-protein cleaving enzyme1 (BACE1), Ng/BACE1 ratio and Amyloid-β 42/40 ratio, phosphorylated-tau and total-tau in LLD with (LLD AD) or without (LLD NoAD) AD pathology, predementia AD and normal controls (NC). We included 145 participants (NC = 41; predementia AD = 66 and LLD = 38). LLD comprised LLD AD (n = 16), LLD NoAD (n = 19), LLD with non-AD typical changes (n = 3, excluded). LLD AD (pADJ < 0.05) and predementia AD (pADJ < 0.0001) showed significantly higher Ng than NC. BACE1 and Ng/BACE1 ratio were altered similarly. Compared to LLD NoAD, LLD AD showed significantly higher Ng (pADJ < 0.001), BACE1 (pADJ < 0.05) and Ng/BACE1 ratio (pADJ < 0.01). All groups had significantly lower Aβ 42/40 ratio than NC (predementia AD and LLD AD, p < 0.0001; LLD NoAD, p < 0.05). Both LLD groups performed similarly on tests of memory and executive function, but significantly poorer than NC. Synaptic function in LLD depended on AD pathology. LLD showed an association to Amyloid dysmetabolism. The LLD groups performed poorer cognitively than NC. LLD AD may be conceptualized as “predementia AD with depression”.

• Wightman, Douglas P.; Jansen, Iris E.; Savage, Jeanne E.; Shadrin, Alexey; Bahrami, Shahram & Holland, Dominic [Vis alle 59 forfattere av denne artikkelen] (2021). A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease. Nature Genetics. ISSN 1061-4036. 53, s. 1276–1282. doi: 10.1038/s41588-021-00921-z. Vis sammendrag

  Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.

• Siafarikas, Nikias Ioannis; Alnæs, Dag; Monereo Sanchez, Jennifer; Lund, Martina J.; Selbæk, Geir & Korsnes, Maria Stylianou [Vis alle 13 forfattere av denne artikkelen] (2021). Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment and Alzheimer's disease with dementia. International Psychogeriatrics. ISSN 1041-6102. 33(11), s. 1217–1228. doi: 10.1017/S1041610221000934. Vis sammendrag

  We present associations between neuropsychiatric symptoms (NPS) and brain morphology in a large sample of patients with mild cognitive impairment (MCI) and Alzheimer’s disease with dementia (AD dementia). Several studies assessed NPS factor structure in MCI and AD dementia, but we know of no study that tested for associations between NPS factors and brain morphology. The use of factor scores increases parsimony and power. For transparency, we performed an additional analysis with selected Neuropsychiatric Inventory – Questionnaire (NPI-Q) items. Including regional cortical thickness, cortical and subcortical volumes, we examined associations between NPS and brain morphology across the whole brain in an unbiased fashion. We reported both statistical significance and effect sizes, using linear models adjusted for multiple comparisons by false discovery rate (FDR). Moreover, we included an interaction term for diagnosis and could thereby compare associations of NPS and brain morphology between MCI and AD dementia. We found an association between the factor elation and thicker right anterior cingulate cortex across MCI and AD dementia. Associations between the factors depression to thickness of the banks of the left superior temporal sulcus and psychosis to the left post-central volume depended on diagnosis: in MCI these associations were positive, in AD dementia negative. Our findings indicate that NPS in MCI and AD dementia are not exclusively associated with atrophy and support previous findings of associations between NPS and mainly frontotemporal brain structures.

• Sønderby, Ida Elken; van der Meer, Dennis; Moreau, Clara; Kaufmann, Tobias; Walters, G. Bragi & Ellegaard, Maria [Vis alle 76 forfattere av denne artikkelen] (2021). 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans. Translational Psychiatry. ISSN 2158-3188. 11. doi: 10.1038/s41398-021-01213-0. Fulltekst i vitenarkiv
• Lorentzen, Ingrid Myrvoll; Espenes, Johan Jacob; Hessen, Erik; Waterloo, Knut; Bråthen, Geir & Timón, Santiago [Vis alle 9 forfattere av denne artikkelen] (2021). Regression-based norms for the FAS phonemic fluency test for ages 40–84 based on a Norwegian sample. Applied neuropsychology: Adult. ISSN 2327-9095. doi: 10.1080/23279095.2021.1918128. Fulltekst i vitenarkiv Vis sammendrag

  The FAS phonemic fluency test is a commonly used neuropsychological test of executive function and processing speed. Although Norwegian discrete norms have been developed for the FAS test, American regression-based norms are frequently used by clinicians in Norway. However, language and cultural differences impact performance on the FAS test, and using foreign norms may not be appropriate. Moreover, while discrete norming relies on stratified subgroups of demographics, regression-based norming uses the entire sample to estimate the influence of demographics on performance and may thus improve normative estimates. Here we develop regression-based norms for the FAS phonemic fluency test based on n = 204 healthy Norwegian controls between the ages 40−84 from the Norwegian Dementia Disease Initiation cohort (DDI). We compare the proposed regression norms to published Norwegian discrete norms and American regression-based norms in an independent sample of n = 182 cognitively healthy adults reporting subjective cognitive decline (SCD). We found that years of education was the only significant predictor of FAS performance in our normative sample, accounting for 14.9% of the variance. Both the proposed regression-based norms and previously published discrete norms adequately adjusted for demographics in the independent sample. In contrast, the American norms underestimated the effect of education and overestimated the effect of age. While both the proposed Norwegian regression norms and the previously published discrete norms are suitable for use in Norway, the proposed regression norms may be less vulnerable to sub-stratification sample characteristics posed by discrete norming procedures, and thereby improve normative estimation.

• Kliem, Elisabeth; Gjestad, Elise Ødegård; Ryum, Truls; Olsen, Alexander; Thommessen, Bente & Indredavik, Bent [Vis alle 10 forfattere av denne artikkelen] (2021). The Relationship of Psychiatric Symptoms with Performance-Based and Self-Reported Cognitive Function After Ischemic Stroke. Journal of the International Neuropsychological Society. ISSN 1355-6177. 28(1), s. 35–47. doi: 10.1017/S1355617721000187. Fulltekst i vitenarkiv Vis sammendrag

  Objective: Findings on the relationship of psychiatric symptoms with performance-based and self-reported cognitive function post-stroke are inconclusive. We aimed to (1) study the relation of depression and anxiety to performance-based cognitive function and (2) explore a broader spectrum of psychiatric symptoms and their association with performance-based versus self-reported cognitive function. Method: Individuals with supratentorial ischemic stroke performed neuropsychological examination 3 months after stroke. For primary analyses, composite scores for memory and attention/executive function were calculated based on selected neuropsychological tests, and the Hospital Anxiety and Depression Scale (HADS) was used. Psychiatric symptoms and self-reported cognitive function for secondary aims were assessed using the Symptom-Checklist-90 – Revised (SCL-90-R). Results: In a sample of 86 patients [mean (M) age: 64.6 ± 9.2; Mini-Mental State Examination (MMSE), 3–7 days post-stroke: M = 28.4 ± 1.7; National Institutes of Health Stroke Scale (NIHSS) after 3 months: M = 0.7 ± 1.6] depressive symptoms (HADS) were associated with poorer memory performance after controlling for age, sex, and education (p ≤ .01). In a subsample (n = 41; Age: M = 65.7 ± 8.1; MMSE: M = 28.4 ± 1.8; NIHSS: M = 1.0 ± 1.9), symptoms of phobic anxiety (SCL-90-R) were associated with poorer performance-based memory and attention/executive function, and symptoms of anxiety (SCL-90-R) with lower attention/executive function. Higher levels of self-reported cognitive difficulties were associated with higher scores in all psychiatric domains (p ≤ .05). Conclusion: Even in relatively well-functioning stroke patients, depressive symptoms are associated with poorer memory. The results also suggest that various psychiatric symptoms are more related to self-reported rather than to performance-based cognitive function. Screening for self-reported cognitive difficulties may not only help to identify patients with cognitive impairment, but also those who need psychological treatment.

• Brooker, Helen; Williams, Gareth; Hampshire, Adam; Corbett, Anne; Aarsland, Dag & Cummings, Jeffrey [Vis alle 14 forfattere av denne artikkelen] (2020). FLAME: A computerized neuropsychological composite for trials in early dementia. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. ISSN 2352-8729. 12(e12098). doi: 10.1002/dad2.12098. Fulltekst i vitenarkiv
• Eliassen, Ingvild Vøllo; Fladby, Tormod; Kirsebom, Bjørn-Eivind; Waterloo, Knut; Eckerström, Marie & Wallin, Anders [Vis alle 9 forfattere av denne artikkelen] (2020). Predictive and diagnostic utility of brief neuropsychological assessment in detecting Alzheimer's pathology and progression to dementia. Neuropsychology. ISSN 0894-4105. 34(8), s. 851–861. doi: 10.1037/neu0000698. Fulltekst i vitenarkiv Vis sammendrag

  Objective: To assess the role of brief neuropsychological assessments in prediction and identification of Alzheimer’s disease (AD) pathology and progression to AD dementia. Method: Adults (N = 255; range = 40–81 years) with self-reported cognitive decline underwent baseline and 2-year follow-up clinical assessment, including a brief neuropsychological screening and lumbar puncture. Five different mild cognitive impairment (MCI) algorithms were applied on baseline cognitive test results: one conventional, three amnestic (lenient, stringent, multidomain), and one comprehensive criterion. We compared predictive and diagnostic accuracy of these MCI criteria by performing logistic regression analyses and calculating diagnostic accuracy measures for 2-year outcomes of (1) clinical diagnosis of AD dementia and (2) cerebrospinal fluid biomarkers in the Alzheimer’s continuum. Results: The lenient amnestic MCI criterion showed the largest effect size for predicting progression to AD dementia (OR = 13.762, 99% CI = 1.969–96.194, p = .001) and AD biomarkers (OR = 4.855, 99% CI = 1.974–11.924, p < .001) after 2 years. This criterion was sensitive for progression to dementia (sensitivity = 92.0%, specificity = 54.8%, positive likelihood ratio [LR+] = 2.03, LR− = 0.15) and showed the highest overall diagnostic accuracy for AD biomarkers (sensitivity = 72.7%, specificity = 59.1%, LR+ = 1.78, negative likelihood ratio [LR−] = 0.46). The multidomain amnestic MCI criterion produced the highest specificity for dementia (sensitivity = 76.0%, specificity = 73.0%, LR+ = 2.82, LR− = 0.33) and AD biomarkers (sensitivity = 46.8% specificity = 70.9% LR+ = 1.61, LR− = 0.75). Conclusions: Defining MCI using a brief neuropsychological battery provided limited accuracy for progression to AD dementia and cerebrospinal fluid Aβ. The lenient amnestic MCI criterion identified the highest number of individuals who progressed to clinical AD or showed biomarker pathology, but this approach included a substantial number of false positives. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

• Rajkumar, Anto P.; Hye, Abdul; Lange, Johannes; Manesh, Yazmin Rashid; Ballard, Clive & Fladby, Tormod [Vis alle 7 forfattere av denne artikkelen] (2020). Next-generation RNA-sequencing of serum small extracellular vesicles discovers potential diagnostic biomarkers for dementia with Lewy bodies. The American journal of geriatric psychiatry. ISSN 1064-7481. s. 1–12. doi: 10.1016/j.jagp.2020.10.012.
• Espenes, Johan Jacob; Hessen, Erik; Eliassen, Ingvild Vøllo; Waterloo, Knut; Eckerström, Marie & Sando, Sigrid Botne [Vis alle 10 forfattere av denne artikkelen] (2020). Demographically adjusted trail making test norms in a Scandinavian sample from 41 to 84 years. The Clinical Neuropsychologist. ISSN 1385-4046. 34, s. 1–18. doi: 10.1080/13854046.2020.1829068. Fulltekst i vitenarkiv Vis sammendrag

  Objective: The trail making test (TMT) is one of the most widely used neuropsychological tests. TMT-A provides measures of visual scanning/visuomotor speed and TMT-B involves additional demands on executive functions. Derived scores TMT B-A and TMT B/A enhance measures of executive functioning. However, simple B-A subtraction may lead to false estimates of executive dysfunction in clinical samples. Norms for TMT have been published in several countries but are currently lacking for Scandinavia. Methods: A total of 292 healthy controls between age 41 and 84 years were included from the Norwegian “Dementia Disease Initiation” (DDI) study (n ¼ 170) and the Gothenburg Mild Cognitive Impairment (MCI) study (n ¼ 122). We used a regression-based procedure to develop demographically adjusted norms for basic (TMT-A and TMT-B) and derived measures (TMT B-A and B/A). We also propose a regression-based alternative to the TMT B-A measure named “TMT-b”. The proposed norms were compared to norms from Heaton et al. and Tombaugh. Results: Due to differences in the estimated normative effects of demographics on performance, the proposed norms for TMT were better suited in the Scandinavian sample compared with published non-Scandinavian norms. The proposed TMT-b measure was highly correlated to TMT B-A (r ¼ 0.969, p < 0.001). Conclusion: We here propose demographically adjusted norms for the TMT for ages 41 through 84 years based on a Scandinavian

• Khalifa, Khadija; Bergland, Anne Katrine; Sønnesyn, Hogne; Oppedal, Ketil; Oesterhus, Ragnhild & Dalen, Ingvild [Vis alle 12 forfattere av denne artikkelen] (2020). Effects of purified anthocyanins in people at risk for dementia: Study protocol for a phase II randomized controlled trial. Frontiers in Neurology. ISSN 1664-2295. 11:916, s. 1–10. doi: 10.3389/fneur.2020.00916. Fulltekst i vitenarkiv
• Ballard, Clive; Aarsland, Dag; Cummings, Jeffrey; O'Brien, John; Mills, Roger & Molinuevo, Jose Luis [Vis alle 11 forfattere av denne artikkelen] (2020). Drug repositioning and repurposing for Alzheimer disease. Nature Reviews Neurology. ISSN 1759-4758. s. 1–13. doi: 10.1038/s41582-020-0397-4.
• Bergland, Anne Katrine; Proitsi, Petroula; Kirsebom, Bjørn-Eivind; Sønnesyn, Hogne; Hye, Abdul & Larsen, Alf Inge [Vis alle 11 forfattere av denne artikkelen] (2020). Exploration of plasma lipids in mild cognitive impairment due to Alzheimer's disease . Journal of Alzheimer's Disease. ISSN 1387-2877. 77(3), s. 1117–1127. doi: 10.3233/JAD-200441.
• Pålhaugen, Lene; Sudre, Carole H; Teceläo, Sandra Raquel Ramos; Nakling, Arne; Almdahl, Ina Selseth & Kalheim, Lisa Flem [Vis alle 13 forfattere av denne artikkelen] (2020). Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns. Journal of Cerebral Blood Flow and Metabolism. ISSN 0271-678X. s. 1–13. doi: 10.1177/0271678X20957604. Fulltekst i vitenarkiv
• Henjum, Kristi; Årskog, Vibeke Helen; Jendresen, Charlotte Bille; Fladby, Tormod; Torp, Reidun & Nilsson, Lars (2020). Analyzing microglial-associated Aβ in Alzheimer’s disease transgenic mice with a novel mid-domain Aβ-antibody. Scientific Reports. ISSN 2045-2322. 10(10590). doi: 10.1038/s41598-020-67419-2. Fulltekst i vitenarkiv
• Espenes, Ragna; Kirsebom, Bjørn-Eivind; Eriksson, Cecilia Magdalena; Waterloo, Knut K; Hessen, Erik & Johnsen, Stein Harald [Vis alle 8 forfattere av denne artikkelen] (2020). Amyloid plaques and symptoms of depression links to medical help-seeking due to subjective cognitive decline. Journal of Alzheimer's Disease. ISSN 1387-2877. 75(3), s. 879–890. doi: 10.3233/JAD-190712. Fulltekst i vitenarkiv
• Fang, Fei; Hou, Y; Palikaras, Konstantinos; Adriaanse, BA; Kerr, SJ & Yang, B [Vis alle 19 forfattere av denne artikkelen] (2019). Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. Nature Neuroscience. ISSN 1097-6256. 22(3), s. 401–412. doi: 10.1038/s41593-018-0332-9.
• van der Meer, Dennis; Sønderby, Ida Elken; Kaufmann, Tobias; Walters, G. Bragi; Abdellaoui, Abdel & Ames, David [Vis alle 132 forfattere av denne artikkelen] (2019). Association of copy number variation of the 15q11.2 BP1-BP2 region with cortical and subcortical morphology and cognition. JAMA psychiatry. ISSN 2168-6238. doi: 10.1001/jamapsychiatry.2019.3779. Vis sammendrag

  IMPORTANCE: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities. OBJECTIVE: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance. DESIGN, SETTING, AND PARTICIPANTS: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019. MAIN OUTCOMES AND MEASURES: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2 , sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort. RESULTS: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = −0.41; SE, 0.08; P = 4.9 × 10−8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10−7), and a smaller nucleus accumbens (Cohen d = −0.27; SE, 0.07; P = 7.3 × 10−5). There was also a significant negative dose response on cortical thickness (β = −0.24; SE, 0.05; P = 6.8 × 10−7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks. CONCLUSIONS AND RELEVANCE: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders

• Creese, Byron; Vassos, Evangelos; Bergh, Sverre; Athanasiu, Lavinia; Johar, Iskandar & Rongve, Arvid [Vis alle 23 forfattere av denne artikkelen] (2019). Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer's disease. Translational Psychiatry. ISSN 2158-3188. 9:273, s. 1–10. doi: 10.1038/s41398-019-0592-5. Fulltekst i vitenarkiv Vis sammendrag

  Psychosis (delusions or hallucinations) in Alzheimer’s disease (AD + P) occurs in up to 50% of individuals and is associated with significantly worse clinical outcomes. Atypical antipsychotics, first developed for schizophrenia, are commonly used in AD + P, suggesting shared mechanisms. Despite this implication, little empirical research has been conducted to examine whether there are mechanistic similarities between AD + P and schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with AD + P. Schizophrenia PRS was calculated using Psychiatric Genomics Consortium data at ten GWAS p value thresholds (PT) in 3111 AD cases from 11 cohort studies characterized for psychosis using validated, standardized tools. Association between PRS and AD + P status was tested by logistic regression in each cohort individually and the results meta-analyzed. The schizophrenia PRS was associated with AD + P at an optimum PT of 0.01. The strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.18-fold increased risk (95% CI: 1.06–1.3; p = 0.001). These new findings point towards psychosis in AD—and particularly delusions—sharing some genetic liability with schizophrenia and support a transdiagnostic view of psychotic symptoms across the lifespan.

• Rongve, Arvid; Witoelar, Aree; Ruiz, Agustín; Athanasiu, Lavinia; Abdelnour, Carla & Clarimon, Jordi [Vis alle 40 forfattere av denne artikkelen] (2019). GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study. Scientific Reports. ISSN 2045-2322. 9. doi: 10.1038/s41598-019-43458-2. Fulltekst i vitenarkiv
• Hope, Tuva Roaldsdatter; Selnes, Per; Rektorová, Irena; Anderkova, Lubomira; Nemcova-Elfmarkova, Nela & Balážová, Zuzana [Vis alle 9 forfattere av denne artikkelen] (2019). Diffusion tensor and restriction spectrum imaging reflect different aspects of neurodegeneration in Parkinson's disease. PLOS ONE. ISSN 1932-6203. 14(5), s. 1–13. doi: 10.1371/journal.pone.0217922. Fulltekst i vitenarkiv
• Fang, Evandro Fei; Hou, Yujun; Palikaras, Konstantinos; Adriaanse, Bryan A.; Kerr, Jesse S. & Yang, Beimeng [Vis alle 20 forfattere av denne artikkelen] (2019). Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. Nature Neuroscience. ISSN 1097-6256. 22(3), s. 401–412. doi: 10.1038/s41593-018-0332-9. Fulltekst i vitenarkiv
• Hessen, Erik; Kirsebom, Bjørn-Eivind; Eriksson, Cecilia Magdalena; Eliassen, Carl Fredrik Andestad; Nakling, Arne & Bråthen, Geir [Vis alle 9 forfattere av denne artikkelen] (2019). In Brief Neuropsychological Assessment, Amnestic Mild Cognitive Impairment (MCI) Is associated with Cerebrospinal Fluid Biomarkers for Cognitive Decline in Contrast to the Prevailing NIA-AA MCI Criterion. Journal of Alzheimer's Disease. ISSN 1387-2877. 67(2), s. 715–723. doi: 10.3233/JAD-180964. Fulltekst i vitenarkiv
• Nordengen, Kaja; Kirsebom, Bjørn-Eivind; Henjum, Kristi; Selnes, Per; Gisladottir, Berglind & Wettergreen, Marianne [Vis alle 12 forfattere av denne artikkelen] (2019). Glial activation and inflammation along the Alzheimer's disease continuum. Journal of Neuroinflammation. ISSN 1742-2094. 16:46, s. 1–13. doi: 10.1186/s12974-019-1399-2. Fulltekst i vitenarkiv
• Kirsebom, Bjørn-Eivind; Espenes, Ragna; Hessen, Erik; Waterloo, Knut; Johnsen, Stein Harald & Gundersen, Elisabeth [Vis alle 10 forfattere av denne artikkelen] (2019). Demographically adjusted CERAD wordlist test norms in a Norwegian sample from 40 to 80 years. The Clinical Neuropsychologist. ISSN 1385-4046. 33, s. 27–39. doi: 10.1080/13854046.2019.1574902. Fulltekst i vitenarkiv
• Jansen, Iris E.; Savage, Jeanne E.; Watanabe, Kyoko; Bryois, Julien; Williams, Dylan M. & Steinberg, Stacy [Vis alle 53 forfattere av denne artikkelen] (2019). Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk. Nature Genetics. ISSN 1061-4036. 51(3), s. 404–413. doi: 10.1038/s41588-018-0311-9. Fulltekst i vitenarkiv
• Knapstad, Mari Kalland; Steihaug, Ole Martin; Aaslund, Mona Kristin; Nakling, Arne; Naterstad, Ingvill Fjell & Fladby, Tormod [Vis alle 8 forfattere av denne artikkelen] (2019). Reduced Walking Speed in Subjective and Mild Cognitive Impairment: A Cross-Sectional Study. Journal of Geriatric Physical Therapy. ISSN 1539-8412. 42(3), s. E122–E128. doi: 10.1519/JPT.0000000000000157.
• Witoelar, Aree; Rongve, Arvid; Almdahl, Ina Selseth; Ulstein, Ingun; Engvig, Andreas & White, Linda Rosemary [Vis alle 33 forfattere av denne artikkelen] (2018). Meta-analysis of Alzheimer’s disease on 9,751 samples from Norway and IGAP study identifies four risk loci. Scientific Reports. ISSN 2045-2322. 8. doi: 10.1038/s41598-018-36429-6. Fulltekst i vitenarkiv
• Kirsebom, Bjørn-Eivind; Nordengen, Kaja; Selnes, Per; Waterloo, Knut; Torsetnes, Silje Bøen & Gisladottir, Berglind [Vis alle 12 forfattere av denne artikkelen] (2018). Cerebrospinal fluid neurogranin/β-site APP-cleaving enzyme 1 predicts cognitive decline in preclinical Alzheimer's disease. Alzheimer's and Dementia: Translational Research and Clinical Interventions. ISSN 2352-8737. 4, s. 617–627. doi: 10.1016/j.trci.2018.10.003. Fulltekst i vitenarkiv
• Jansen, Willemijn J.; Ossenkoppele, Rik; Tijms, Betty M.; Fagan, Anne M.; Hansson, Oskar & Klunk, William E. [Vis alle 57 forfattere av denne artikkelen] (2018). Association of cerebral amyloid-β aggregation with cognitive functioning in persons without dementia. JAMA psychiatry. ISSN 2168-6238. 75(1), s. 84–95. doi: 10.1001/jamapsychiatry.2017.3391.
• Mattsson, Niklas; Groot, Colin; Jansen, Willemijn J.; Landau, Susan M.; Villemagne, Victor L. & Engelborghs, Sebastiaan [Vis alle 95 forfattere av denne artikkelen] (2018). Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease. Alzheimer's & Dementia. ISSN 1552-5260. 14(7), s. 913–924. doi: 10.1016/j.jalz.2018.02.009.
• Kalheim, Lisa Flem; Fladby, Tormod; Coello, Christopher; Bjørnerud, Atle & Selnes, Per (2018). [18F]-Flutemetamol Uptake in Cortex and White Matter: Comparison with Cerebrospinal Fluid Biomarkers and [18F]-Fludeoxyglucose. Journal of Alzheimer's Disease. ISSN 1387-2877. 62(4), s. 1595–1607. doi: 10.3233/JAD-170582. Fulltekst i vitenarkiv
• Siafarikas, Nikias; Selbæk, Geir; Fladby, Tormod; Saltyte Benth, Jurate; Auning, Eirik & Aarsland, Dag (2018). Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer's disease. International Psychogeriatrics. ISSN 1041-6102. 30(1), s. 103–113. doi: 10.1017/S1041610217001879.
• Olafsson, Sigurgeir; Olafsson, S.; Stridh, Pernilla; Stridh, P.; Bos, Steffan Daniel & Ingason, Andrés [Vis alle 72 forfattere av denne artikkelen] (2017). Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations. NPJ GENOMIC MEDICINE. ISSN 2056-7944. 2. doi: 10.1038/s41525-017-0027-2. Fulltekst i vitenarkiv Vis sammendrag

  A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.

• Selnes, Per; Stav, Ane Løvli; Johansen, Krisztina Kunszt; Bjørnerud, Atle; Coello, Christopher & Auning, Eirik [Vis alle 13 forfattere av denne artikkelen] (2017). Impaired synaptic function is linked to cognition in Parkinson's disease. Annals of clinical and translational neurology. ISSN 2328-9503. 4(10), s. 700–713. doi: 10.1002/acn3.446.
• Eliassen, Carl F Andestad; Reinvang, Ivar; Selnes, Per; Grambaite, Ramune; Fladby, Tormod & Hessen, Erik (2017). Biomarkers in subtypes of mild cognitive impairment and subjective cognitive decline. Brain and Behavior. ISSN 2162-3279. 7(9). doi: 10.1002/brb3.776.
• Nakling, Arne; Aarsland, Dag; Næss, Halvor; Wollschläger, Daniel; Fladby, Tormod & Hofstad, Håkon [Vis alle 7 forfattere av denne artikkelen] (2017). Cognitive deficits in chronic stroke patients: neuropsychological assessment, depression, and self-reports. Dementia and Geriatric Cognitive Disorders Extra. ISSN 1664-5464. 7(2), s. 283–296. doi: 10.1159/000478851.
• Fladby, Tormod; Pålhaugen, Lene; Selnes, Per; Waterloo, Knut; Bråthen, Geir & Hessen, Erik [Vis alle 27 forfattere av denne artikkelen] (2017). Detecting at-risk Alzheimer's disease cases. Journal of Alzheimer's Disease. ISSN 1387-2877. 60(1), s. 97–105. doi: 10.3233/JAD-170231.
• Kirsebom, Bjørn-Eivind Seljelid Bordewic; Espenes, Ragna; Waterloo, Knut; Hessen, Erik; Johnsen, Stein Harald & Bråthen, Geir [Vis alle 8 forfattere av denne artikkelen] (2017). Screening for Alzheimer’s Disease: Cognitive Impairment in Self-Referred and Memory Clinic-Referred Patients. Journal of Alzheimer's Disease. ISSN 1387-2877. 60(4), s. 1621–1631. doi: 10.3233/JAD-170385. Fulltekst i vitenarkiv
• Zamorano, Mariano Rincón; Díaz-López, Estela; Selnes, Per; Vegge, Kjetil; Altmann, Marianne & Fladby, Tormod [Vis alle 7 forfattere av denne artikkelen] (2017). Improved Automatic Segmentation of White Matter Hyperintensities in MRI Based on Multilevel Lesion Features. Neuroinformatics. ISSN 1539-2791. 15(3), s. 231–245. doi: 10.1007/s12021-017-9328-y.
• Eliassen, Carl F Andestad; Reinvang, Ivar; Selnes, Per; Fladby, Tormod & Hessen, Erik (2017). Convergent Results from Neuropsychology and from Neuroimaging in Patients with Mild Cognitive Impairment. Dementia and Geriatric Cognitive Disorders. ISSN 1420-8008. 43(3-4), s. 144–154. doi: 10.1159/000455832.
• Hessen, Erik; Eckerström, Marie; Nordlund, Arto; Almdahl, Ina; Stålhammar, Jacob & Bjerke, Maria [Vis alle 11 forfattere av denne artikkelen] (2017). Subjective cognitive impairment is a predominantly benign condition in memory clinic patients followed for 6 years: The Gothenburg-oslo MCI Study. Dementia and Geriatric Cognitive Disorders Extra. ISSN 1664-5464. 7(1), s. 1–14. doi: 10.1159/000454676.
• Almdahl, Ina; Lauridsen, Camilla; Selnes, Per; Kalheim, Lisa Flem; Coello, Christopher & Gajdzik, Beata [Vis alle 14 forfattere av denne artikkelen] (2017). Cerebrospinal fluid levels of amyloid beta 1-43 mirror 1-42 in relation to imaging biomarkers of Alzheimer's disease. Frontiers in Aging Neuroscience. ISSN 1663-4365. 9, s. 1–13. doi: 10.3389/fnagi.2017.00009. Fulltekst i vitenarkiv
• Styrkarsdóttir, Unnur; Helgason, Hannes; Sigurdsson, Asgeir; Norddahl, Gudmundur L.; Agustsdottir, Arna B. & Reynard, Louise N. [Vis alle 48 forfattere av denne artikkelen] (2017). Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis. Nature Genetics. ISSN 1061-4036. 49(5), s. 801–805. doi: 10.1038/ng.3816.
• Kalheim, Lisa Flem; Bjørnerud, Atle; Fladby, Tormod; Vegge, Kjetil & Selnes, Per (2017). White matter hyperintensity microstructure in amyloid dysmetabolism. Journal of Cerebral Blood Flow and Metabolism. ISSN 0271-678X. 37(1), s. 356–365. doi: 10.1177/0271678X15627465.
• Lillenes, Meryl Sønderby; Støen, Mari; Günther, Clara-Cecilie; Selnes, Per; Stenset, Vidar & Espeseth, Thomas [Vis alle 9 forfattere av denne artikkelen] (2017). Mitochondrial transcription factor A (TFAM) rs1937 and AP endonuclease 1 (APE1) rs1130409 alleles are associated with reduced cognitive performance. Neuroscience Letters. ISSN 0304-3940. 645, s. 46–52. doi: 10.1016/j.neulet.2017.02.062. Vis sammendrag

  Mitochondrial dysfunction and DNA damage is intimately connected to ageing and neurodegeneration, including Alzheimer’s disease (AD). A particular culprit in this context is oxidative stress, which is a result of increased reactive oxygen species (ROS) due to hyperactive or dysfunctional mitochondria and/or reduced DNA repair capacity. Base excision repair (BER) is the major pathway for repairing oxidative damage events in chromosomal and mitochondrial DNA. Defects in BER have been detected in ageing and neurodegeneration. Mitochondrial transcription factor A (TFAM) plays an important role in the maintenance of mitochondrial DNA integrity. The present study investigated single nucleotide polymorphisms (SNPs) in the genes encoding the BER components MutYH, OGG1, APE1, PolB and PolG and the gene encoding mitochondrial TFAM in a cohort of 161 AD patients, 96 non-AD patient controls (PC) and 192 healthy controls (HC). Notably, the minor allele carriers of APE1 rs1130409 and the common allele carriers of TFAM rs1937 were associated with reduced mini-mental state examination score in AD patients, PC and HC, with no distinction of SNP frequencies in either of these sub-groups. Collectively, the results suggest an association between DNA maintenance and decline in cognitive function. These studies enlighten the normal brain aging process and point to potential new biomarkers for cognitive function and impairment.

• Kalheim, Lisa Flem; Selnes, Per; Bjørnerud, Atle; Coello, Christopher; Vegge, Kjetil & Fladby, Tormod (2016). Amyloid dysmetabolism relates to reduced glucose uptake in white matter hyperintensities. Frontiers in Neurology. ISSN 1664-2295. 7. doi: 10.3389/fneur.2016.00209.
• Stav, Ane Løvli; Johansen, Krisztina Kunszt; Auning, Eirik; Kalheim, Lisa Flem; Selnes, Per & Bjørnerud, Atle [Vis alle 9 forfattere av denne artikkelen] (2016). Hippocampal subfield atrophy in relation to cerebrospinal fluid biomarkers and cognition in early Parkinson’s disease: a cross-sectional study. NPJ Parkinson's Disease. ISSN 2373-8057. 2. doi: 10.1038/npjparkd.2015.30. Fulltekst i vitenarkiv
• Van Steenoven, Inger; Aarsland, Dag; Weintraub, Daniel; Londos, Elisabet; Blanc, Frédéric & van der Flier, Wiesje M. [Vis alle 12 forfattere av denne artikkelen] (2016). Cerebrospinal fluid Alzheimer's disease biomarkers across the spectrum of lewy body diseases: Results from a large multicenter cohort. Journal of Alzheimer's Disease. ISSN 1387-2877. 54(1), s. 287–295. doi: 10.3233/JAD-160322.
• Lillenes, Meryl Sønderby; Rabano, Alberto; Støen, Mari; Riaz, Tahira; Misaghian, Dorna & Møllersen, Linda [Vis alle 12 forfattere av denne artikkelen] (2016). Altered DNA base excision repair profile in brain tissue and blood in Alzheimer’s disease. Molecular Brain. ISSN 1756-6606. 9:61, s. 1–14. doi: 10.1186/s13041-016-0237-z. Vis sammendrag

  Background: Alzheimer’s disease (AD) is a progressive, multifactorial neurodegenerative disorder that is the main cause of dementia globally. AD is associated with increased oxidative stress, resulting from imbalance in production and clearance of reactive oxygen species (ROS). ROS can damage DNA and other macromolecules, leading to genome instability and disrupted cellular functions. Base excision repair (BER) plays a major role in repairing oxidative DNA lesions. Here, we compared the expression of BER components APE1, OGG1, PARP1 and Polβ in blood and postmortem brain tissue from patients with AD, mild cognitive impairment (MCI) and healthy controls (HC). Results: BER mRNA levels were correlated to clinical signs and cerebrospinal fluid biomarkers for AD. Notably, the expression of BER genes was higher in brain tissue than in blood samples. Polβ mRNA level was significantly higher in the cerebellum than in the other brain regions, more so in AD patients than in HC. Blood mRNA levels of OGG1 was low and PARP1 high in MCI and AD. Conclusions: These findings suggest that alteration in BER gene expression is an event preceding AD and reflect the oxidative stress-generating energy-consumption in the brain and the importance of BER in repairing these damage events. The results link DNA repair in brain and blood to the etiology of AD at the molecular level and can potentially serve in establishing novel biomarkers, particularly in the AD prodromal phase.

• Hessen, Erik; Stav, Ane Løvli; Auning, Eirik; Selnes, Per; Blomsø, Linn & Holmeide, Cathrine Emilie [Vis alle 11 forfattere av denne artikkelen] (2016). Neuropsychological profiles in mild cognitive impairment due to Alzheimer's and Parkinson's diseases. Journal of Parkinson's Disease. ISSN 1877-7171. 6(2), s. 413–421. doi: 10.3233/JPD-150761.
• Henjum, Kristi; Almdahl, Ina; Årskog, Vibeke Helen; Minthon, Lennart; Hansson, Oskar & Fladby, Tormod [Vis alle 7 forfattere av denne artikkelen] (2016). Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease. Alzheimer's Research & Therapy. ISSN 1758-9193. 8(1). doi: 10.1186/s13195-016-0182-1.
• Andreasen, Niels; Simeoni, Monica; Ostlund, Henrik; Lisjo, Pia I.; Fladby, Tormod & Loercher, Amy E. [Vis alle 18 forfattere av denne artikkelen] (2015). First administration of the Fc-attenuated anti-β amyloid antibody GSK933776 to patients with mild Alzheimer's disease: A randomized, placebo-controlled study. PLOS ONE. ISSN 1932-6203. 10(3). doi: 10.1371/journal.pone.0098153.

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• Hemminghyth, Mathilde Suhr; Breitve, Monica Haraldseid; Gisladottir, Berglind; Grøntvedt, Gøril Rolfseng; Nakling, Arne Exner & Fladby, Tormod [Vis alle 8 forfattere av denne artikkelen] (2023). Cerebrospinal fluid neurofilament light chain mediates age-related decline in learning and memory in healthy adults.
• Becu, Marcia Constance Noemi; Bonnevie, Tora; Polti, Ignacio; Jarholm, Jonas Alexander; Grøntvedt, Gøril Rolfseng & Bråthen, Geir [Vis alle 9 forfattere av denne artikkelen] (2022). Entorhinal grid-like representation in early Alzheimer's disease: association with biomarkers concentration and genetic risk.
• Siafarikas, Nikias Ioannis; Kirsebom, Bjørn-Eivind; Srivastava, Deepak P.; Eriksson, Cecilia Magdalena; Auning, Eirik & Hessen, Erik [Vis alle 10 forfattere av denne artikkelen] (2022). Author Correction: Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression (Scientific Reports, (2021), 11, 1, (20375), 10.1038/s41598-021-99794-9). Scientific Reports. ISSN 2045-2322. 12(1). doi: 10.1038/s41598-022-22274-1.
• Wightman, Douglas P.; Jansen, Iris E.; Savage, Jeanne E.; Shadrin, Alexey; Bahrami, Shahram & Holland, Dominic [Vis alle 114 forfattere av denne artikkelen] (2022). Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease (Nature Genetics, (2021), 53, 9, (1276-1282), 10.1038/s41588-021-00921-z). Nature Genetics. ISSN 1061-4036. 54(7). doi: 10.1038/s41588-022-01126-8.
• Wightman, Douglas P.; Jansen, Iris E.; Savage, Jeanne E.; Shadrin, Alexey A.; Bahrami, Shahram & Holland, Dominic [Vis alle 114 forfattere av denne artikkelen] (2021). Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease (Nature Genetics, (2021), 53, 9, (1276-1282), 10.1038/s41588-021-00921-z). Nature Genetics. ISSN 1061-4036. doi: 10.1038/s41588-021-00977-x.
• Espenes, Johan Jacob; Eliassen, Ingvild Vøllo; Fladby, Tormod; Eckerström, Marie; Anders, Wallin & Waterloo, Knut [Vis alle 8 forfattere av denne artikkelen] (2020). Demographically adjusted test norms for the Rey Auditory Verbal Learning Test in Norwegian and Swedish adults from 41 to 79 years.
• Kliem, Elisabeth; Gjestad, Elise Ødegård; Ryum, Truls; Olsen, Alexander; Thommessen, Bente & Indredavik, Bent [Vis alle 9 forfattere av denne artikkelen] (2020). Relations Between Psychiatric Symptoms, Performance-based and Self-Reported Cognitive Function After Stroke .
• Rongve, Arvid; Witoelar, Aree Widya; Ruiz, Agustín; Athanasiu, Lavinia; Abdelnour, Carla & Clarimon, Jordi [Vis alle 40 forfattere av denne artikkelen] (2019). Author Correction: GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study (Scientific Reports, (2019), 9, 1, (7013), 10.1038/s41598-019-43458-2). Scientific Reports. ISSN 2045-2322. 9(1). doi: 10.1038/s41598-019-51827-0.
• Eliassen, Ingvild Vøllo; Kirsebom, Bjørn-Eivind; Hessen, Erik; Selnes, Per; Waterloo, Knut & Fladby, Tormod (2019). Distractor List Errors from Verbal Learning Test May Reveal Deficient Temporal Memory Encoding in Predementia Alzheimer’s Disease .
• Kirsebom, Bjørn-Eivind; Selnes, Per; Richter, Grit; Gisladottir, Berglind; Wettergreen, Marianne & Torsetnes, Silje Bøen [Vis alle 9 forfattere av denne artikkelen] (2019). Cerebrospinal fluid Neurogranin/BACE1 ratio differentiate normal controls, pre-dementia Alzheimer’s and Parkinson’s disease cases.
• Espenes, Johan Jacob; Kirsebom, Bjørn-Eivind; Eliassen Vøllo, Ingvild; Espenes, Ragna; Waterloo, Knut & Hessen, Erik [Vis alle 7 forfattere av denne artikkelen] (2019). Demographically adjusted norms for basic and derived measures on the Trail Making Test A & B based on a Norwegian sample age 40 – 84 years.
• Richter, Grit; Kirsebom, Bjørn-Eivind; Selnes, Per; Nordengen, Kaja; Waterloo, Knut & Gisladottir, Berglind [Vis alle 12 forfattere av denne artikkelen] (2019). An amyloid-coupled pre-dementia increased CSF neurogranin/BACE1 ratio may reflect early synapse affection in APOE-ɛ4 homozygotes.
• Espenes, Ragna; Kirsebom, Bjørn-Eivind; Eriksson, Cecilia Magdalena; Waterloo, Knut; Johnsen, Stein Harald & Hessen, Erik [Vis alle 7 forfattere av denne artikkelen] (2019). Medical help-seeking in Subjective Cognitive Decline associated with lower CSF Aβ1-42 and reduced memory performance.
• Da Silva, Miguel Vasconcelos; Creese, Byron; Iskandar, Johar; Aarsland, Dag; Bergh, Sverre & Athanasiu, Lavinia [Vis alle 20 forfattere av denne artikkelen] (2019). Genome wide Association study: identifying Genetic markers in apathy in People with Alzheimer's disease. Alzheimer's & Dementia. ISSN 1552-5260. 15, s. P286–P286. doi: 10.1016/j.jalz.2019.06.686.
• Richter, Grit; Kirsebom, Bjørn-Eivind; Selnes, Per; Nordengen, Kaja; Waterloo, Knut & Gisladottir, Berglind [Vis alle 12 forfattere av denne artikkelen] (2019). Early increase in CSF neurogranin/BACE1 ratio in predementia APOE-ɛ4 homozygote cases with amyloid pathology .
• Kvås, Inger-Lise; Saltvedt, Ingvild & Fladby, Tormod (2018). Ja, du kan forebygge demens. [Avis]. Norsk ukeblad.
• Grambaite, Ramune; Selnes, Per; Hessen, Erik & Fladby, Tormod (2018). Memory intrusions and CSF biomarkers in subjective and mild cognitive impairment.
• Kirsebom, Bjørn-Eivind; Nordengen, Kaja; Selnes, Per; Waterloo, Knut; Brix, Britta & Vanmechelen, Eugeen [Vis alle 8 forfattere av denne artikkelen] (2018). INCREASED CSF NEUROGRANIN/BACE1 RATIO IN AMYLOID POSITIVE SUBJECTS WITH SUBJECTIVE COGNITIVE DECLINE.
• Kirsebom, Bjørn-Eivind; Espenes, Ragna; Waterloo, Knut; Johnsen, Stein Harald & Fladby, Tormod (2017). Screening for Alzheimer's Disease: Cognitive Impairent in Self-Referred and Memory Clinic-Referred Patients.
• Lillenes, Meryl Sønderby; Riaz, Tahira; Rabano, Alberto; Fladby, Tormod & Tonjum, Tone (2016). Altered DNA base excision repair profile in brain tissue and blood in Alzheimer's disease. Vis sammendrag

  Alzheimer’s disease (AD) is the major contributor to cognitive decline and dementia worldwide. Considering the expanding numbers of elderly in our society, studies of health and disease in the aging population is increasingly important. In order to understand AD, one must understand normal aging. AD is preceded by mild cognitive impairment (MCI), and once MCI occurs, early diagnostics and therapies are urgently needed. MCI/AD is associated with increased oxidative stress, resulting from imbalance in production and clearance of reactive oxygen species (ROS). ROS can damage DNA and other macromolecules, leading to genome instability and disrupted cellular functions. To counteract the harmful effects of oxidative DNA damage, cells use the base excision repair (BER) pathway. We have monitored the expression of the DNA repair profile in human blood and post-mortem brain biopsies from AD and MCI patients and healthy aged individuals by transcriptional profiling and mass spectrometry. In this context, we have a particular a focus on selected BER components, to define if the expression profile varies between AD patients as compared to healthy controls. Notably, BER expression was significantly higher in brain tissue compared to blood. BER mRNA levels were correlated to clinical signs and cerebrospinal fluid biomarkers for AD. Blood mRNA levels of OGG1 was low and PARP1 high in MCI and AD. These findings suggest that alteration in BER gene expression is an event preceding AD and reflect the oxidative stress-generating energy-consumption in the brain and the importance of BER in repairing these damage events. Collectively, these studies provide new keys to understanding early events in the progression of AD and also expand the pool of potential biomarkers for pre-clinical AD

• Skogseth, Ragnhild Eide; Aarsland, Dag; Gilhus, Nils Erik & Fladby, Tormod (2019). Biomarker and pathology studies in neurodegenerative cognitive impairment . Universitetet i Bergen. ISSN 9788230865682.

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