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Background Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer's disease (AD) vary by the genetic risk of AD and related dementias (ADD) is unknown. Methods This study included 148 659 older adults of white British ancestry (aged ≥60 years) participating in UK Biobank with no dementia, and self-reported poor health status at baseline. Polygenic risk scores (PRS) for ADD were calculated based on 64 genetic variants. Grip strength was measured by hand dynamometers. Results The hazard ratios (HR) of dementia (n  = 4 963) and AD (n  = 2 373) for high genetic risk of ADD were 2.36 (95% confidence interval [CI]: 2.15–2.59) and 3.00 (95% CI: 2.61–3.44), respectively, compared with low genetic risk. Compared with the bottom tertile of grip strength, the top tertile of grip strength had a hazard ratio (HR) of 0.69 (95% CI: 0.64–0.74) for incident dementia, and 0.74 (95% CI: 0.66–0.82) for incident AD, after adjustment for confounders and PRS for ADD. The risk of dementia and AD was lower with the top grip strength tertile within each level of genetic susceptibility to ADD. There was no evidence of multiplicative interaction between grip strength and genetic susceptibility to ADD for both dementia (p value:.241) and AD (p value:.314). Conclusions Older adults with higher PRS for ADD are at higher risk of developing dementia and AD. The risk of dementia and AD was lower in individuals with higher grip strength, regardless of their level of genetic susceptibility to ADD. [ABSTRACT FROM AUTHOR]

Background: Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable‐device‐measured ST with physical activity (PA) is unknown. Objectives: To examine the associations of wearable‐device‐measured ST replaced by PA with incident CHD across strata of genetic susceptibility. Methods: This study included 77,500 White British (57% female) with valid wrist‐worn accelerometry and without prevalent CHD/stroke from UK Biobank. Genetic susceptibility to CHD was quantified through weighted polygenic risk scores for CHD based on 300 single‐nucleotide polymorphisms. Wrist‐worn accelerometer data were used to derive ST, light PA, and moderate‐to‐vigorous PA (MVPA). Results: Reallocation of 60 min/day of ST into the same amount of MVPA was associated with approximately 9% lower relative risk of CHD for all participants and across strata of genetic risk: replacement of 1 min/day of ST associated with <1% lower relative risk of CHD. No evidence of interaction (p: 0.784) was found between genetic risk and ST for CHD risk. Reallocating 60 min/day of ST into the same MVPA time was associated with greater absolute CHD risk reductions at high genetic risk (0.27%) versus low genetic risk (0.15%). Conclusions: Replacing any amount of ST with an equal amount of MVPA time is associated with a lower relative risk of CHD, irrespective of genetic susceptibility to CHD. Reductions in CHD absolute risk for replacing ST with MVPA are greater at high genetic risk versus low genetic risk. [ABSTRACT FROM AUTHOR]