Ola Nakken

• Dahl, Iselin Teresa; Dhami, Sanpreet Kaur Grewal; Sousa, Diana Aguiar de; Nakken, Ola; Zarnovicky, Svetozar & Faiz, Kashif Waqar [Vis alle 9 forfattere av denne artikkelen] (2026). Enhancing risk prediction for cerebral venous thrombosis: evaluation of an integrated approach with clinical CVT probability score and D-dimer levels. BMC Neurology. 26(1). doi: 10.1186/s12883-026-04687-x. Fulltekst i vitenarkiv
• Solheim, Magne Haugland; Riise, Trond; Cortese, Marianna; Nakken, Ola; Tysnes, Ole-Bjørn & Igland, Jannicke [Vis alle 7 forfattere av denne artikkelen] (2026). Distinct Prescription Patterns Emerge Years Before ALS Diagnosis: A Nationwide Registry-Based Study. Annals of Neurology. ISSN 0364-5134. 99(6), s. 1516–1525. doi: 10.1002/ana.78191. Fulltekst i vitenarkiv Vis sammendrag

  Objective: The prodromal phase of amyotrophic lateral sclerosis (ALS) is poorly defined. We aimed to characterize prescription drug use patterns in the pre-diagnostic period by analyzing nationwide prescription data to identify the earliest divergence between individuals who developed ALS and matched healthy controls. We used this divergence as an indirect marker to estimate the onset and duration of the prodrome. Methods: We conducted a nested case-control study using nationwide Norwegian registries (2005–2019). ALS cases were individually matched to 100 controls by sex, age, and education level using incidence density sampling. Drug prescription data were gathered from the Norwegian Prescription Database (NorPD). We calculated prescription rates up to 10 years before diagnosis, performed lag-time analyses, and used machine learning to predict ALS based on drug prescription patterns. Results: We identified 2,084 incident patients with ALS and 208,400 matched healthy controls. Overall, changes in prescription patterns occurred 2 to 3 years before ALS diagnosis. Among specific drug groups, 25 of 42 therapeutic drug classes were prescribed more frequently to patients with ALS than matched controls. Muscle relaxants and bone disease treatments were prescribed significantly more frequently 6 and 5 years before diagnosis, respectively. Interpretation: Prescription pattern changes occurred as early as 6 years before ALS diagnosis. These findings are consistent with a prodromal phase preceding the clinical stage of ALS, which may last several years. In contrast, the broad increase in medication use during the final year before diagnosis likely reflects increased health care utilization as patients seek treatment for the various emerging symptoms of the clinically manifest disease.

• Johansen, Henriette; Nakken, Ola; Holmøy, Trygve & Fredheim, Olav Magnus Søndenå (2026). Disease trajectories and end of life care in a Norwegian ALS cohort. BMC Neurology. 26(1). doi: 10.1186/s12883-026-04698-8. Fulltekst i vitenarkiv
• Nakken, Ola; Vaage, Anders Myhre; Stigum, Hein; Bjørnevik, Kjetil Lauvland; Holmøy, Trygve & Meyer, Haakon Eduard (2025). Duration of Current Statin Use and Amyotrophic Lateral Sclerosis Risk: A Norwegian Population-Based Cohort Study. Neurology. ISSN 0028-3878. 105(8). doi: 10.1212/WNL.0000000000214221. Fulltekst i vitenarkiv
• Vaage, Anders Myhre; Holmøy, Trygve; Dahl, Jesper; Stigum, Hein; Meyer, Haakon Eduard & Nakken, Ola (2025). Statin Use and Amyotrophic Lateral Sclerosis Survival: A Population-Based Cohort Study. European Journal of Neurology. ISSN 1351-5101. 32(3). doi: 10.1111/ene.70095. Fulltekst i vitenarkiv Vis sammendrag

  Background Dyslipidemia is common in amyotrophic lateral sclerosis (ALS). Statin use has been associated with both favorable and poor prognoses. We assessed whether statin use affects ALS survival. Methods We linked four Norwegian health surveys (1972–2003) with mandatory national registries to obtain information on premorbid health, ALS diagnosis, and death. Using the Norwegian Prescribed Drug Registry, we identified participants who had dispensed statins pre- and post-diagnosis. We first compared pre-diagnosis statin discontinuation rates between ALS patients and matched controls. Flexible parametric models were then fitted to estimate the relationship between statin use and survival time in ALS, using restricted mean survival time and hazard ratio (HR) as effect measures. Results A total of 524 patients (43% female) with ALS were included. Mean time from ALS diagnosis to death or end of study was 2.0 (SD 2.1) years. A substantial proportion of statin users (21%) discontinued statins during the year leading up to diagnosis. This group was characterized by poorer ALS prognosis compared to those adhering to statins and were included as statin users in our analysis. After adjusting for sex, age, birth year, riluzole use and premorbid smoking status, body mass index, and total cholesterol levels, statin use was not associated with ALS survival. The estimated mean survival difference comparing statin users to non-users was 0.74 (95% CI −5.98 to 7.47) months, corresponding to a HR of 0.97 (95% CI 0.77–1.23). Conclusion Statin use was not associated with ALS survival, suggesting that statins should not routinely be discontinued in ALS.

• Olsen, Cathrine Goberg; Malmberg, Vetle Nilsen; Fahlström, Maria; Alstadhaug, Karl Bjørnar; Bjørnå, Ingrid Kristine & Braathen, Geir Julius [Vis alle 24 forfattere av denne artikkelen] (2024). Amyotrophic lateral sclerosis caused by the C9orf72 expansion in Norway–prevalence, ancestry, clinical characteristics and sociodemographic status. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. ISSN 2167-8421. 26(1-2), s. 132–140. doi: 10.1080/21678421.2024.2405118. Fulltekst i vitenarkiv Vis sammendrag

  Objective: The most common genetic cause of amyotrophic lateral sclerosis (ALS) is the C9orf72 expansion. A high incidence of this expansion has been detected in Sweden and Finland. This Norwegian population-based study aimed to identify the prevalence, geographic distribution, ancestry, and relatedness of ALS patients with a C9orf72 expansion (C9pos). Further, we compared C9pos and C9neg patients' clinical presentation, family history of ALS and other neurodegenerative disorders, and sociodemographic status. Methods: We recruited ALS patients from all 17 Departments of neurology in Norway. Blood samples and questionnaires regarding clinical characteristics, sociodemographic status and family history of ALS, and other neurodegenerative disorders were collected. The C9orf72 expansion was examined for all patients. Results: The study enrolled 500 ALS patients, 8.8% of whom were C9pos, with half being sporadic ALS cases. The proportion of C9pos cases differed between regions, ranging from 17.9% in the Northern

• Nakken, Ola; Aarseth, Jan Harald; Wergeland, Stig; Stigum, Hein; Meyer, Haakon E. & Holmøy, Trygve (2024). BCG vaccination and multiple sclerosis risk: A Norwegian cohort study. Multiple Sclerosis. ISSN 1352-4585. 30(6), s. 646–653. doi: 10.1177/13524585241230440. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Bacillus Calmette–Guérin (BCG) vaccination induces long-lasting effects on the adaptive and innate immune systems and prevents development of experimental autoimmune encephalomyelitis and possibly also inflammatory disease activity in multiple sclerosis (MS). Objective: The objective is to examine if BCG given in early adulthood decreases MS risk. Methods: From 791,369 (52% females) Norwegians participating in a national tuberculosis screening program from 1963 to 1975, we collected information on BCG vaccination and tuberculosis disease status. Later, MS disease was ascertained through both the Norwegian MS Registry and Biobank and the Norwegian Death Registry. We used logistic regression models to assess the relationship between BCG vaccination and MS risk. Results: In those BCG vaccinated, mean age at vaccination was 15.6 (standard deviation (SD) = 5.5) years. A total of 2862 (65% females) MS cases were retrieved. Overall, we found no association between MS risk and BCG vaccination. Compared to non-BCG-vaccinated individuals with no signs of tuberculosis infection, odds ratio (OR) for MS was 1.00 (95% confidence interval (CI) = 0.80–1.25) in the BCG-vaccinated group. In those not BCG vaccinated because of latent tuberculosis infection, the corresponding OR was 0.86 (95% CI = 0.66–1.13). Conclusion: We found no evidence of BCG vaccination or latent tuberculosis infection in young adulthood being linked to MS risk.

• Vaage, Anders Myhre; Meyer, Haakon Eduard; Landgraff, Ida Kalstad; Myrstad, Marius; Holmøy, Trygve & Nakken, Ola (2024). Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study. Neurology. ISSN 0028-3878. 103(2). doi: 10.1212/WNL.0000000000209575. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objectives Observational studies have demonstrated an increased amyotrophic lateral sclerosis (ALS) risk among professional athletes in various sports. For moderately increased levels of physical activity and fitness, the results are diverging. Through a cohort study, we aimed to assess the relationship between indicators of physical activity and fitness (self-reported physical activity and resting heart rate) and long-term ALS risk. Methods From a large Norwegian cardiovascular health survey (1985–1999), we collected information on self-reported physical activity in leisure time, resting heart rate, and other cardiovascular risk factors. Patients with ALS were identified through health registries covering the whole population. We fitted Cox proportional hazard models to assess the risk of ALS according to levels of self-reported physical activity in 3 categories (1: sedentary; 2: minimum 4 hours per week of walking or cycling; 3: minimum 4 hours per week of recreational sports or hard training), and resting heart rate modeled both on the continuous scale and as quartiles of distribution. Results Out of 373,696 study participants (mean 40.9 [SD 1.1] years at inclusion), 504 (41.2% women) developed ALS during a mean follow-up time of 27.2 (SD 5.0) years. Compared with participants with the lowest level of physical activity, the hazard ratio was 0.71 (95% CI 0.53–0.95) for those with the highest level. There were no clear associations between resting heart rate and ALS in the total sample. In men, the hazard ratio of ALS was 0.71 (95% CI 0.53–0.95) for those reporting moderate levels of physical activity and 0.59 (95% CI 0.42–0.84) for those reporting high levels, compared with those reporting low levels. Men with resting heart rate in the lowest quartile had 32% reduced risk of ALS (hazard ratio 0.68, 95% CI 0.49–0.94) compared with those in the second highest quartile. In women, no association was detected between neither self-reported levels of physical activity nor resting heart rate and ALS risk. Discussion Indicators of high levels of physical activity and fitness are associated with a reduced risk of ALS more than 30 years later in men, but not in women.

• Novy, Camilla; Busk, Øyvind; Tysnes, Ole-Bjørn; Landa, Sigve Strand; Aanjesen, Tori Navestad & Alstadhaug, Karl Bjørnar [Vis alle 29 forfattere av denne artikkelen] (2024). Repeat expansions in AR, ATXN1, ATXN2 and HTT in Norwegian patients diagnosed with amyotrophic lateral sclerosis. Brain Communications. 6(2), s. 1–10. doi: 10.1093/braincomms/fcae087. Fulltekst i vitenarkiv Vis sammendrag

  Genetic repeat expansions cause neuronal degeneration in amyotrophic lateral sclerosis as well as other neurodegenerative disorders such as spinocerebellar ataxia, Huntington’s disease and Kennedy’s disease. Repeat expansions in the same gene can cause multiple clinical phenotypes. We aimed to characterize repeat expansions in a Norwegian amyotrophic lateral sclerosis cohort. Norwegian amyotrophic lateral sclerosis patients (n = 414) and neurologically healthy controls adjusted for age and gender (n = 713) were investigated for repeat expansions in AR, ATXN1, ATXN2 and HTT using short read exome sequencing and the ExpansionHunter software. Five amyotrophic lateral sclerosis patients (1.2%) and two controls (0.3%) carried ≥36 repeats in HTT (P = 0.032), and seven amyotrophic lateral sclerosis patients (1.7%) and three controls (0.4%) carried ≥29 repeats in ATXN2 (P = 0.038). One male diagnosed with amyotrophic lateral sclerosis carried a pathogenic repeat expansion in AR, and his diagnosis was revised to Kenne

• Vaage, Anders Myhre; Benth, Jurate Saltyte; Meyer, Haakon Eduard; Holmøy, Trygve & Nakken, Ola (2023). Premorbid lipid levels and long-term risk of ALS—a population-based cohort study. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. ISSN 2167-8421. doi: 10.1080/21678421.2023.2295455. Fulltekst i vitenarkiv Vis sammendrag

  Objective To assess the temporal relationship between premorbid lipid levels and long-term amyotrophic lateral sclerosis (ALS) risk. Methods From Norwegian cardiovascular health surveys (1974–2003), we collected information on total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, and other cardiovascular risk factors. ALS incidence and mortality were identified through validated Norwegian health registries. The relation between premorbid lipid levels and ALS risk was assessed by Cox regression models. Results Out of 640,066 study participants (51.5% females), 974 individuals (43.5% females) developed ALS. Mean follow-up time was 23.7 (SD 7.1) years among ALS cases. One mmol/l increase in LDL-C was associated with 6% increase in risk for ALS (hazard ratio 1.06 [95% CI: 1.01–1.09]). Higher levels of TC and TG were also associated with increased ALS risk, but only within the last 6–7 years prior to ALS diagnosis or death. No association between HDL-C and ALS risk was found. Adjusting for body mass index, birth cohort, smoking, and physical activity did not alter the results. Conclusions Higher levels of LDL-C are associated with increased ALS risk over 40 years later, compatible with a causal relationship. The temporal relationship between TG, TC, and ALS risk suggests that increased levels of these lipid biomarkers represent consequences of ALS.

• Nakken, Ola; Vaage, Anders Myhre; Stigum, Hein; Heldal, Einar; Meyer, Haakon E. & Holmøy, Trygve (2023). Tuberculin responses after BCG vaccination predict amyotrophic lateral sclerosis risk. Brain, Behavior, and Immunity - Health (BBI - Health). 34, s. 1–6. doi: 10.1016/j.bbih.2023.100704. Fulltekst i vitenarkiv Vis sammendrag

  Background T cell infiltration around dying motor neurons is a hallmark of amyotrophic lateral sclerosis (ALS). It is not known if this immune response represents a cause or a consequence of the disease. We aimed to establish whether individual variation in regulation of a T cell driven immune response is associated with long-term ALS risk. Methods Tuberculin skin test (TST) following BCG vaccination represents a standardized measure of a secondary T cell driven immune response. During a Norwegian tuberculosis screening program (1963–1975) Norwegian citizens born from 1910 to 1955 underwent TST. In those previously BCG vaccinated (median 7 years prior to TST), we related tuberculin skin tests to later ALS disease identified through validated Norwegian health registers. We fitted Cox proportional hazard models to investigate the association between tuberculin reactivity and ALS risk. Results Among 324,629 participants (52 % women) with median age 22 (IQR 10) years at tuberculosis screening, 496 (50 % women) later developed ALS. Hazard ratio for ALS was 0.74 (95% CI 0.57–0.95) for those who remained TST negative compared to those who mounted a positive TST. The association was strongest when time between BCG immunization and TST was short. The associations observed persisted for more than four decades after TST measurement. Conclusions Negative TST responses after BCG vaccination is associated with decreased long-term risk for ALS development, supporting a primary role for adaptive immunity in ALS development.

• Høyer, Helle; Nakken, Ola & Holmøy, Trygve (2023). A Novel SPAST Variant Associated with Isolated Spastic Paraplegia. Case Reports in Genetics. ISSN 2090-6552. doi: 10.1155/2023/4553365. Fulltekst i vitenarkiv Vis sammendrag

  Genetic variants in SPAST are the most common cause of hereditary spastic paraplegia (HSP), entitled spastic paraplegia type 4 (SPG4). Inheritance is autosomal dominant, and age of onset can vary from childhood to adulthood. Pathogenic SPAST variants are often observed in isolated cases, likely due to reduced penetrance and clinical variability. We report an isolated case of SPG4 associated with a novel likely pathogenic variant in SPAST. A 38-year-old woman presented with an eight-year history of progressive difficulty walking. Neurological examination revealed spastic paraparesis in the absence of upper motor neuron dysfunction, sensory deficits, or intellectual disability. Magnetic resonance imaging (MRI) of the brain and spinal cord was normal. No family members had similar complaints. Genetic analysis revealed a novel heterozygous sequence variant in SPAST, c.1751A > G p.(Asp584Gly) (NM_014946.4). The affected amino acid is highly conserved among orthologue and paralogue species. Four other nucleotide substitutions predicted to affect the same amino acid, a "hot spot", have been reported previously in adult-onset HSP. This report describes a novel SPAST variant in a female with HSP without a known family history of the disorder.

• Olsen, Cathrine Goberg; Busk, Øyvind Løvold; Aanjesen, Tori Navestad; Alstadhaug, Karl Bjørnar; Bjørnå, Ingrid Kristine & Braathen, Geir Julius [Vis alle 28 forfattere av denne artikkelen] (2022). Genetic Epidemiology of Amyotrophic lateral Sclerosis in Norway: A 2-Year Population-Based Study. Neuroepidemiology. ISSN 0251-5350. 56(4), s. 271–282. doi: 10.1159/000525091. Fulltekst i vitenarkiv Vis sammendrag

  Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40-70% of familial ALS patients and approximately in 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. Methods: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. Results: A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected with ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region. Conclusion: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well.

• Nakken, Ola; Holmøy, Trygve; Stigum, Hein; Myhr, Kjell-Morten; Dahl, Jesper & Heldal, Einar [Vis alle 7 forfattere av denne artikkelen] (2022). Strong tuberculin response after BCG vaccination is associated with low multiple sclerosis risk: a population-based cohort study. International Journal of Epidemiology. ISSN 0300-5771. 51(5), s. 1637–1644. doi: 10.1093/ije/dyac039. Fulltekst i vitenarkiv Vis sammendrag

  Background: Multiple sclerosis (MS) is characterized by inflammatory lesions in the central nervous system involving pro-inflammatory T-cells. Immune dysregulation is well described in prevalent disease, but it is not known whether this precedes disease development. Bacillus Calmette–Guerin (BCG) vaccination ameliorates MS-like disease in mice. In people vaccinated with BCG, the tuberculin skin test (TST) offers a standardized measure of a T-cell-mediated immune response. We therefore hypothesized that the strength of the TST response after BCG vaccination is associated with subsequent MS risk. Methods: Using data from a Norwegian tuberculosis screening programme (1963–1975), we designed a population-based cohort study and related the size of TST reactions in individuals previously vaccinated with BCG to later MS disease identified through the Norwegian MS registry. We fitted Cox proportional hazard models and flexible parametric survival models to investigate the association between TST reactivity, MS risk and its temporal relationship. Results: Among 279 891 participants (52% females), 679 (69% females) later developed MS. Larger TST reactivity was associated with decreased MS risk. The hazard ratio for MS per every 4-mm increase in skin induration size was 0.86 (95% confidence interval 0.76–0.96) and similar between sexes. The strength of the association persisted for >30 years after the TST. Conclusion: A strong in vivo vaccine response to BCG is associated with reduced MS risk >30 years later. The immunological mechanisms determining TST reactivity suggest that skewed T-cell-mediated immunity precedes MS onset by many decades.

• Høglund, Rune Alexander; Meyer, Haakon Eduard; Stigum, Hein; Torkildsen, Øivind; Grytten, Nina & Holmøy, Trygve [Vis alle 7 forfattere av denne artikkelen] (2021). Association of body mass index in Adolescence and young Adulthood and long-term risk of multiple Sclerosis: A Population-Based Study. Neurology. ISSN 0028-3878. 97(23), s. E2253–E2261. doi: 10.1212/WNL.0000000000012957. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objectives To prospectively investigate the long-term relationship between body mass index (BMI) in adolescents and young adults and risk for multiple sclerosis (MS) at the population level. Methods We used data from the population-based compulsory Norwegian tuberculosis screening program during 1963 to 1975, including objectively measured height and weight from ≈85% of all eligible citizens. This was combined with data from the Norwegian MS registry and biobank up to November 2020. BMI was standardized according to age and sex, and risk for MS was calculated with Cox proportional hazard models. Results During 30,829,506 years of follow-up, we found 1,409 cases of MS among 648,734 participants in eligible age groups (14–34 years). Overall, obesity was associated with increased MS risk (hazard ratio [HR] 1.53 [95% confidence interval (CI) 1.25–1.88]), and the risk was similar in men (HR 1.4 [95% CI 0.95–2.06] and women (HR 1.59 [95% CI 1.25–2.02]). Risk was highest for the youngest age groups (age 14–16: HR 1.73 [95% CI 1.19–2.53]; 17–19: HR 1.61 [95% CI 1.08–2.39]; 20–24: HR 1.56 [95% CI 1.04–2.36]) and was no longer present for those >30 years of age. Discussion High BMI in individuals 14 to 24 years of age was associated with increased MS risk later in life in both male and female individuals.

• Nakken, Ola; Meyer, Haakon E; Stigum, Hein & Holmøy, Trygve (2019). High BMI is associated with low ALS risk: A population-based study. Neurology. ISSN 0028-3878. 93(5), s. e424–e432. doi: 10.1212/WNL.0000000000007861. Fulltekst i vitenarkiv Vis sammendrag

  This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased. Abstract Objective To investigate the temporal relationship among prediagnostic body mass index (BMI), weight change, and risk of amyotrophic lateral sclerosis (ALS). Methods From the compulsory Norwegian tuberculosis screening program, we collected objectively measured BMI from 85% of all citizens (near 1.5 million) between 20 and 70 years of age living in 18 of 19 Norwegian counties between 1963 and 1975. For those who participated in later health surveys, we collected further information on weight change, lifestyle, and health. We identified ALS cases until September 2017 through national registries of diagnoses at death and at encounters with the specialist health service. Both Cox hazard models and flexible parametric survival models were fitted to address our research question. Results We identified 2,968 ALS cases during a mean of 33 (maximum 54) years follow-up. High prediagnostic BMI was associated with low subsequent ALS risk across the typical ALS ages in both sexes. Overall, hazard ratio (HR) for ALS per 5-unit increase in prediagnostic BMI was 0.83 (95% confidence interval [CI] 0.79–0.88). After an initial increase during the first 10 years, it decreased almost linearly throughout the observation period and was 0.69 (95% CI 0.62–0.77) after 50 years. Those in the quartile with highest weight gain had lower ALS risk than those in the lowest quartile (HR 0.63, 95% CI 0.44–0.89). Conclusion High BMI and weight gain are associated with low ALS risk several decades later. The strength of the association between BMI and ALS risk increases up to 50 years after BMI measurement.

• Nakken, Ola; Lindstrøm, Jonas Christoffer & Holmøy, Trygve (2018). Sex ratio in multiple sclerosis mortality over 65 years; an age-period-cohort analysis in Norway. Journal of Neurology. ISSN 0340-5354. 265(6), s. 1295–1302. doi: 10.1007/s00415-018-8832-9. Fulltekst i vitenarkiv Vis sammendrag

  Increasing female: male ratio in multiple sclerosis (MS) has been assigned to cohort effects, with females in more recent birth cohorts possibly being more exposed or vulnerable to environmental risk factors than males. We collected MS mortality data in Norway from 1951 to 2015 from The Norwegian Cause of Death registry. Age-Period-Cohort analysis was conducted using log-linear Poisson models, including sex interaction terms. MS was registered as the underlying, contributing or direct cause in 6060 deaths. MS associated mortality remained stable with a slight preponderance among males until after 1980, and have since increased preferentially among females. Throughout the study period the mean annual increase was 1.25% for females and 0.3% for males (p < 0.0001). Age-period-cohort analysis revealed limited evidence of cohort effects for the gender differences; the best fitting model only included gender-age and gender-period interaction terms. The period effect evened out for males in the last three decades but increased for females, especially among the oldest age-groups. In conclusion, the increased female: male mortality ratio in MS associated mortality is driven mainly by increased mortality among females in the three last decades, particularly in the older age groups. It is best explained by disproportional period effects, providing evidence of time-varying external factors including improved access to diagnosis among females.

• Nakken, Ola; Sørum, Lillian & Holmøy, Trygve (2018). Genetisk utredning ved amyotrofisk lateral sklerose. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(13). doi: 10.4045/tidsskr.18.0193. Fulltekst i vitenarkiv
• Nakken, Ola; Lindstrøm, Jonas Christoffer; Tysnes, Ole-Bjørn & Holmøy, Trygve (2018). Assessing amyotrophic lateral sclerosis prevalence in Norway from 2009 to 2015 from compulsory nationwide health registers. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. ISSN 2167-8421. 19(3-4), s. 303–310. doi: 10.1080/21678421.2017.1418004. Fulltekst i vitenarkiv Vis sammendrag

  Objective: In Norway, diagnoses from specialist health care visits, drug prescriptions, and causes of deaths are registered in compulsory health registers. We aimed to determine amyotrophic lateral sclerosis (ALS) prevalence from 2009 to 2015 by combining these registers. Methods:We validated the Norwegian Patient Registry (NPR) through hospital files, and linked it with the Norwegian Cause of Death Registry and the Norwegian Prescription Database. Poisson regression models were fitted for estimating gender ratios, time trends and possible interactions. Similar models were used for mortality data subtracted from the dataset. Results: Eleven percent of patients with at least one ALS-related entry in NPR did not have ALS. ALS prevalence could nevertheless be reliably estimated through ascertaining cases identified in two separate registers, or with at least two entries in NPR with first entry within four years prior to prevalence date. ALS prevalence remained stable, and was 7.6/100,000 (95% CI 6.9–8.4) at 31st December 2015. Mean male:female ratio was higher for prevalence (1.8; 95% CI 1.6–2.0) than for mortality (1.5; 95% CI 1.2–1.8) (p¼0.04). There were also significant regional differences in prevalence (p50.01) but not in mortality. Conclusions: Norwegian compulsory health registers provide reliable tools for ALS surveillance, and suggest gender and regional differences in survival after diagnosis.

• Nakken, Ola; Lindstrøm, Jonas Christoffer; Tysnes, Ole-Bjørn & Holmøy, Trygve (2016). Mortality trends of amyotrophic lateral sclerosis in Norway 1951–2014: an age–period–cohort study. Journal of Neurology. ISSN 0340-5354. s. 1–8. doi: 10.1007/s00415-016-8273-2. Fulltekst i vitenarkiv Vis sammendrag

  Recent studies suggest that the incidence and mortality of amyotrophic lateral sclerosis (ALS) are increasing. Changing environmental factors could influence disease risk differently throughout life span, and also between genders, birth cohorts, and seasons of birth. We aimed at describing long-term ALS mortality trends in Norway between 1951 and 2014 using age–period–cohort analysis. The Norwegian Cause of Death Registry provided ALS mortality data that were age- and sex-adjusted through direct standardization. Poisson regression analyses were used for identification of mortality trends and potential month of birth effects. We identified 5345 ALS cases, of which 54.7 % were men. ALS mortality increased throughout the whole period (p < 0.001), with a mean annual increase of 1.14 %. The increase was confined to those older than 60 years, but rates consistently dropped amongst the absolute oldest. The increase was mainly driven by birth cohort effects that increased from 1860 until 1934 (p < 0.001). No month of birth effect or change in sex ratio was found. The continuous increase in ALS mortality since 1951 is best explained by the long-term changes in exposure to risk factors or in case ascertainment, affecting men and women equally in the generations born since 1860 and at least into 1934.

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• Glover, Joel; Tysnes, Ole-Bjørn; Myhr, Kjell-Morten; Bråthen, Geir; Sandvig, Ioanna & Høyer, Helle [Vis alle 9 forfattere av denne artikkelen] (2019). Hvor står ALS-forskningen i Norge? Fulltekst i vitenarkiv
• Nakken, Ola & Holmøy, Trygve (2018). Rett til ikke å vite og amyotrofisk lateral sklerose. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(16), s. 1502–1502. doi: 10.4045/tidsskr.18.0734. Fulltekst i vitenarkiv

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