| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
- Sindi, S., et al.
(författare)
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Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline : A Randomized Clinical Trial
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 76:3, s. 491-498
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs). METHODS: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989). RESULTS: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264). CONCLUSIONS: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits. CLINICAL TRIALS REGISTRATION NUMBER: NCT01041989.
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| 3. |
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| 4. |
- Kulmala, J., et al.
(författare)
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Association between mid- to late life physical fitness and dementia : evidence from the CAIDE study
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 276:3, s. 296-307
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. This study investigated the association between perceived physical fitness at midlife, changes in perceived fitness during the three decades from mid-to late life and dementia risk. Design. Prospective cohort study. Setting. Cardiovascular risk factors, ageing and incidence of dementia (CAIDE) study. Subjects. Subjects were selected from four independent, random samples of population-based cardiovascular surveys and were first examined in 1972, 1977, 1982 or 1987, when they were on average 50 years old. The CAIDE target population included 3559 individuals. A random sample of 2000 individuals still alive in 1997 was drawn for re-examinations (performed in 1998 and 2005-2008) that consisted of cognitive assessments, with 1511 subjects participating in at least one re-examination. Dementia diagnoses were also confirmed from national registers for the entire target population. Main outcome measure. All-cause dementia. Results. Poor physical fitness at midlife was associated with increased dementia risk in the entire target population [hazard ratio (HR), 1.5; 95% confidence interval (CI), 1.1-2.0]. In participants, odds ratio (OR) was 2.0 (95% CI, 0.9-4.0). This association was significant in apolipoprotein E epsilon 4 allele (APO epsilon 4) noncarriers (OR, 4.3; 95% CI, 1.4-13.3), men (HR, 1.8; 95% CI, 1.1-3.0) and people with chronic conditions (HR, 2.9; 95% CI, 1.3-6.6). A decline in fitness after midlife was also associated with dementia (OR, 3.0; 95% CI, 1.7-5.1), which was significant amongst both men and women and more pronounced in APOE epsilon 4 carriers (OR, 4.4; 95% CI, 2.1-9.1). Conclusions. Perceived poor physical fitness reflects a combination of biological and lifestyle-related factors that can increase dementia risk. A simple question about perceived physical fitness may reveal at-risk individuals who could benefit from preventive interventions.
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| 5. |
- Sindi, S., et al.
(författare)
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Midlife improvements in financial situation are associated with a reduced dementia risk later in life : the CAIDE 30-year study
- 2020
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 32:11, s. 1317-1324
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Perceived financial strain is associated with various health conditions, but it is unknown whether it is associated with an increased risk for dementia. The goal is to examine the associations between midlife perceptions of financial situation and dementia risk later in life.Methods: Participants were derived from the Cardiovascular Risk Factors, Aging, and Dementia population-based cohort study (n = 2000) (between 1972 and 1987, baseline mean age 50 years) in Finland. Participants returned for two re-examinations in late life (in 1998 and 2005–2008, mean age 71 and 78 years). In this study, 1442 subjects that participated in at least one re-examination (mean total follow-up 25 years) were included in analyses. Financial strain was measured using two questions in midlife on perceptions of financial situation and perceptions of changes in financial situation. For each question, participants were categorized into three groups reporting improvement, worsening, or stability, with the latter set as the reference group. Analyses were adjusted for potential confounding factors.Results: The group reporting better financial situation had a reduced risk for dementia (fully adjusted model: odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33–0.86). In contrast, the group reporting worse financial situation did not have an increased risk for dementia (OR: 1.04, 95% CI: 0.53–2.02). Analyses on perceptions of current financial situation showed that the groups reporting satisfaction or dissatisfaction with financial situation did not differ in risk for dementia.Conclusion: This study is the first to show that midlife improvements in financial situation are associated with a reduced dementia risk later in life. Potential pathways related to stress reduction, improved lifestyle, and potential biological mechanisms are discussed.
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| 6. |
- Solomon, A., et al.
(författare)
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Self-rated physical fitness and estimated maximal oxygen uptake in relation to all-cause and cause-specific mortality
- 2018
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 28:2, s. 532-540
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the longitudinal associations of self-rated physical fitness and estimated maximal oxygen uptake (VO2max) with all-cause and cause-specific mortality. A total of 59741 participants in the Finnish National FINRISK Study Cohort had data on self-rated physical fitness and covariates. A subsample of 4823 participants had estimated VO2max data. Follow-up ranged from 3 to 38years. Associations of self-rated physical fitness and VO2max with mortality were analyzed using multivariate Cox proportional hazard models. The study showed that poor self-rated physical fitness was related to all-cause mortality (hazard ratio [HR] 1.9; 95% confidence interval [CI] 1.8-2.0) and mortality due to cardiovascular (HR 2.0, 95% CI 1.9-2.2), cerebrovascular (HR 1.9, 95% CI 1.6-2.2) and respiratory diseases (HR 2.1, 95% CI 1.9-2.4), trauma (HR 1.7, 95% CI 1.3-2.0), infections (HR 1.8, 95% CI 1.3-2.7), dementia (HR 1.9, 95% CI 1.6-2.3), and cancer (HR 1.7, 95% CI 1.5-1.9). Coexisting higher age, physical inactivity, male gender, and severe chronic conditions further increased the risk. In men, higher VO2max was associated with a lower risk of lung cancer mortality (HR 0.8, 95% CI 0.7-0.96). Based on the results, self-rated physical fitness reflects a combination of unfavorable biological and lifestyle-related factors, which increase mortality risk. A simple question about perceived physical fitness may reveal at-risk individuals who would benefit from more intensive treatment of chronic conditions and other interventions aiming to promote better fitness and well-being.
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| 7. |
- Hooshmand, Babak, et al.
(författare)
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Homocysteine and holotranscobalamin and the risk of Alzheimer disease : a longitudinal study
- 2010
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 75:16, s. 1408-1414
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the relation between serum levels of homocysteine (tHcy) and holotranscobalamin (holoTC), the active fraction of vitamin B12, and risk of incident Alzheimer disease (AD) in a sample of Finnish community-dwelling elderly. METHODS: A dementia-free sample of 271 subjects aged 65-79 years derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed up for 7 years to detect incident AD. The association between serum tHcy and holoTC with AD was analyzed with multiple logistic regression after adjusting for several potential confounders, including common vascular risk factors. RESULTS: The odds ratios (ORs) (95% confidence interval [CI]) for AD were 1.16 (1.04-1.31) per increase of 1 μmol/L of tHcy at baseline and 0.980 (0.965-0.995) for each increase of 1 pmol/L baseline holoTC. Adjustment for several potential confounders including age, sex, education, APOE ε4 allele, body mass index, Mini-Mental State Examination, smoking, stroke, and blood pressure did not alter the associations: ORs (95% CI) for AD became 1.19 (1.01-1.39) for tHcy and 0.977 (0.958-0.997) for holoTC. Adjusting for holoTC attenuated the tHcy-AD link (OR changed from 1.16 to 1.10, 95% CI 0.96-1.25). The holoTC-AD relationship was less influenced by controlling for tHcy (OR changed from 0.980 to 0.984, 95% CI 0.968-1.000). Addition of folate did not change any of the results. CONCLUSIONS: This study suggests that both tHcy and holoTC may be involved in the development of AD. The tHcy-AD link may be partly explained by serum holoTC. The role of holoTC in AD should be further investigated.
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| 8. |
- Solomon, A, et al.
(författare)
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Lipid-lowering treatment is related to decreased risk of dementia : a population-based study (FINRISK)
- 2010
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Ingår i: Neurodegenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 7:1-3, s. 180-182
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several lines of evidence have linked cholesterol to dementia.OBJECTIVE: To investigate lipid-lowering drug use and dementia development in a Finnish population.METHODS: FINRISK is a large population-based survey of cardiovascular risk factors carried out since 1972 every 5 years using independent, random and representative population samples from different parts of Finland. Several cohorts were part of the WHO-MONICA study. Data from cohorts 1972-2002 were linked to the Hospital Discharge Registry and Drug Reimbursement Registry (1995-2007) to ascertain dementia diagnoses and lipid-lowering treatment. Selection criteria for the study were: (1) alive and without dementia in 1995; (2) age > or = 60 years (in 1995 for earlier cohorts and in 1997 or 2002 for later cohorts; (3) treatment prescribed at least 1 year before dementia diagnosis.RESULTS: 17,597 persons were included in the study. Lipid-lowering treatment was related to decreased dementia risk. In Cox proportional hazards model, hazard ratio (95% CI) was 0.42 (0.37-0.49; controlled for age, sex, education, survey region, survey year, baseline cholesterol, body mass index and systolic blood pressure).CONCLUSION: Preliminary results from the FINRISK study indicate that lipid-lowering drugs may have a beneficial effect in dementia prevention. Further data linkage is ongoing in order to investigate the roles of different types of lipid-lowering drugs.
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