AbstractBackgroundImpaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late‐life dementia (after 80 years of age). We examined whether hand grip strength and timed‐up‐and‐go (TUG) performance, including their change over 5 years, were associated with late‐life dementia events in older women and whether any associations provided independent information to Apolipoprotein Eℇ4 (APOEℇ4) genotype.MethodsGrip strength and TUG were assessed in community‐dwelling older women (mean ± SD; age 75.0 ± 2.6 years) at baseline (n= 1225) and 5 years (n= 1052). Incident 14.5‐year late‐life dementia events (dementia‐related hospitalization/death) were obtained from linked health records. Cardiovascular risk factors (Framingham Risk Score),APOEgenotyping, prevalent atherosclerotic vascular disease and cardiovascular‐related medications were evaluated at baseline. These were included in multivariable‐adjusted Cox‐proportional hazards models assessing the relationship between muscle function measures and late‐life‐dementia events.ResultsOver follow‐up, 207 (16.9%) women had a late‐life dementia event. Compared with women with the highest grip strength (Quartile [Q] 4, 25.8 kg), those with the lowest grip strength (Q1, 16.0 kg) had greater hazard for a late‐life dementia event (HR 2.27 95% CI 1.54–3.35,P< 0.001). For TUG, the slowest women (Q4, 12.4 vs. Q1, 7.4 s) also recorded a greater hazard for a late‐life dementia event (HR 2.10 95% CI 1.42–3.10,P= 002). Weak hand grip (<22 kg) or slow TUG (>10.2 s) provided independent information to the presence of anAPOEℇ4 allele (n= 280, 22.9%). Compared with women with no weakness and noAPOEℇ4 allele, those with weakness andAPOEℇ4 allele had a greater hazard (HR 3.19 95% CI 2.09–4.88,P< 0.001) for a late‐life dementia event. Women presenting with slowness and theAPOEℇ4 allele also recorded a greater hazard for a late‐life dementia event (HR 2.59 95% CI 1.64–4.09,P< 0.001). For 5‐year muscle function changes, compared with women with the lowest performance decrement (Q1), those with the largest decrement (Q4) had higher hazards for a late‐life dementia event (grip strength HR 1.94 95% CI 1.22–3.08,P= 0.006; TUG HR 2.52 95% CI 1.59–3.98,P< 0.001) over the next 9.5 years.ConclusionsWeaker grip strength and slower TUG, and a greater decline over 5 years, were significant risk factors for a late‐life‐dementia event in community‐dwelling older women, independent of lifestyle and genetic risk factors. Incorporating muscle function measures as part of dementia screening appears useful to identify high‐risk individuals who might benefit from primary prevention programmes.