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- 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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| 3. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Lehtisalo, J., et al.
(författare)
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Association of long-term dietary fat intake, exercise, and weight with later cognitive function in the Finnish Diabetes Prevention Study
- 2016
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 20:2, s. 146-154
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate associations of long-term nutrient intake, physical activity and obesity with later cognitive function among the participants in the Finnish Diabetes Prevention Study, in which a lifestyle intervention was successful in diabetes prevention. Design: An active lifestyle intervention phase during middle age (mean duration 4 years) and extended follow-up (additional 9 years) with annual lifestyle measurements, followed by an ancillary cognition assessment. Setting: 5 research centers in Finland. Participants: Of the 522 middle-aged, overweight participants with impaired glucose tolerance recruited to the study, 364 (70%) participated in the cognition assessment (mean age 68 years). Measurements: A cognitive assessment was executed with the CERAD test battery and the Trail Making Test A on average 13 years after baseline. Lifestyle measurements included annual clinical measurements, food records, and exercise questionnaires during both the intervention and follow-up phase. Results: Lower intake of total fat (p=0.021) and saturated fatty acids (p=0.010), and frequent physical activity (p=0.040) during the whole study period were associated with better cognitive performance. Higher BMI (p= 0.012) and waist circumference (p= 0.012) were also associated with worse performance, but weight reduction prior to the cognition assessment predicted worse performance as well (decrease vs. increase, p= 0.008 for BMI and p= 0.002 for waist). Conclusions: Long-term dietary fat intake, BMI, and waist circumference have an inverse association with cognitive function in later life among people with IGT. However, decreases in BMI and waist prior to cognitive assessment are associated with worse cognitive performance, which could be explained by reverse causality.
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| 7. |
- Kivipelto, Miia, et al.
(författare)
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World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia
- 2020
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094
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Tidskriftsartikel (refereegranskat)abstract
- Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
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| 8. |
- Kulmala, J, et al.
(författare)
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Leisure-Time and Occupational Physical Activity in Early and Late Adulthood in Relation to Later Life Physical Functioning
- 2016
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Ingår i: Journal of physical activity & health. - : Human Kinetics. - 1543-5474 .- 1543-3080. ; 13:10, s. 1079-1087
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) has beneficial effects on older age physical functioning, but longitudinal studies with follow-ups extending up to decades are few. We investigated the association between leisure-time PA (LTPA) and occupational PA (OPA) from early to late adulthood in relation to later life performance-based physical functioning.Methods:The study involved 1260 people aged 60 to 79 years who took part in assessments of physical functioning (Short Physical Performance Battery [SPPB] test, 10-m maximal walking test, and grip strength test). Participants’ data on earlier life LTPA/OPA (age range 25 to 74 years) were received from the previous studies (average follow-up 13.4 years). Logistic, linear, and censored regression models were used to assess the associations between LTPA/OPA earlier in life and subsequent physical functioning.Results:A high level of LTPA earlier in life was associated with a lower risk of having difficulties on the SPPB test (odds ratio [OR]: 0.37; 95% confidence interval [CI], 0.24–0.58) and especially on the chair rise test (OR: 0.42; 95% CI, 0.27–0.64) in old age. Heavy manual work predicted difficulties on SPPB (OR: 1.91; 95% CI, 1.22–2.98) and the chair rise test (OR: 1.75; 95% CI, 1.14–2.69) and poorer walking speed (β = .10, P = .005).Conclusions:This study highlights the importance of LTPA on later life functioning, but also indicates the inverse effects that may be caused by heavy manual work.
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