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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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- Kaaja, R., et al.
(författare)
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Effects of sympatholytic therapy on insulin sensitivity indices in hypertensive postmenopausal women
- 2007
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Ingår i: Int J Clin Pharmacol Ther. - 0946-1965. ; 45:7, s. 394-401
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular risk factors are often ineffectively controlled in hypertensive postmenopausal women, and moreover, some antihypertensive drugs may increase particular risk factors such as insulin resistance. In a multicenter, multinational (Finland, Sweden, Lithuania), double-blind, prospectively randomized study hypertensive obese postmenopausal women without hormone therapy (n = 98) were randomly assigned to receive treatment with either the centrally acting agent moxonidine, 0.6 mg/day, or with the peripherally acting atenolol, 50 mg/day, for 8 weeks. In addition to blood pressure measurements, insulin sensitivity was estimated by the quantitative insulin sensitivity check index (QUICKI) and by the insulin sensitivity index (ISI-Matsuda). Subgroup analysis in insulin-resistant women (fasting P-insulin > or = 10 mU/l) and blood pressure responders (diastolic blood pressure < or = 90 mmHg and/or reduction of blood pressure > or = 10 mmHg) were also carried out. Both atenolol and moxonidine led to a significant reduction in diastolic blood pressure of 9.5 mmHg and 6.2 mmHg, respectively. Among insulin-resistant women, an increase in the insulin sensitivity assessed by ISI was improved with moxonidine treatment (p = 0.025). A decrease in insulin sensitivity assessed by QUICKI was observed with atenolol treatment in women with fasting insulin level < 10 mU/l. In patients, in whom blood pressure was reduced, an improvement in insulin sensitivity (ISI) was associated with moxonidine treatment (p = 0.019), but not with atenolol treatment. The centrally acting sympatholytic agent moxonidine did reduce blood pressure somewhat less than atenolol, but it was associated with an improved metabolic profile in terms of decreased insulin resistance both in insulin-resistant postmenopausal women and in women with a significant blood pressure response.
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- 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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- Peters, R., et al.
(författare)
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Evaluation of High Cholesterol and Risk of Dementia and Cognitive Decline in Older Adults Using Individual Patient Meta-Analysis
- 2021
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 50, s. 318-325
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. Method: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. Results: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. Conclusion: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia.
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