Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis

Abstract

ObjectiveTo examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises from changes in physical activity in the preclinical (prodromal) phase of dementia.DesignMeta-analysis of 19 prospective observational cohort studies.Data sourcesThe Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies.Review methodThe search strategy was designed to retrieve individual-participant data from prospective cohort studies. Exposure was physical inactivity; primary outcomes were incident all-cause dementia and Alzheimer’s disease; and the secondary outcome was incident cardiometabolic disease (that is, diabetes, coronary heart disease, and stroke). Summary estimates were obtained using random effects meta-analysis.ResultsStudy population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical inactivity at study entry, and were linked to electronic health records. In 6.0 million person-years at risk, we recorded 2044 incident cases of all-cause dementia. In studies with data on dementia subtype, the number of incident cases of Alzheimer’s disease was 1602 in 5.2 million person-years. When measured <10 years before dementia diagnosis (that is, the preclinical stage of dementia), physical inactivity was associated with increased incidence of all-cause dementia (hazard ratio 1.40, 95% confidence interval 1.23 to 1.71) and Alzheimer’s disease (1.36, 1.12 to 1.65). When reverse causation was minimised by assessing physical activity ≥10 years before dementia onset, no difference in dementia risk between physically active and inactive participants was observed (hazard ratios 1.01 (0.89 to 1.14) and 0.96 (0.85 to 1.08) for the two outcomes). Physical inactivity was consistently associated with increased risk of incident diabetes (hazard ratio 1.42, 1.25 to 1.61), coronary heart disease (1.24, 1.13 to 1.36), and stroke (1.16, 1.05 to 1.27). Among people in whom cardiometabolic disease preceded dementia, physical inactivity was non-significantly associated with dementia (hazard ratio for physical activity assessed >10 before dementia onset 1.30, 0.79 to 2.14).ConclusionsIn analyses that addressed bias due to reverse causation, physical inactivity was not associated with all-cause dementia or Alzheimer’s disease, although an indication of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.

Physical activity and risk of Alzheimer’s disease: a two-sample Mendelian randomization study

“…Given the increase in life expectancy, AD is increasingly a public health challenge and measures to prevent or delay the onset of dementia are urgently needed. However, in combination with previous literature [13,14], the present study provides little evidence that recommending physical activity would help to prevent AD. Table 1 Mendelian randomization estimates between accelerometer-based physical activity and Alzheimer's disease…”

Physical inactivity and cardiovascular disease at the time of coronavirus disease 2019 (COVID-19)

“…11 A recent meta-analysis of prospective studies, totalling 36 investigations and over three million subjects followed up for a median period of 12 years, concluded that achieving the WHO recommended physical activity levels was associated with 17% lower risk of cardiovascular events (relative risk (RR), 0.83; 95% confidence interval (CI), 0.77-0.89), 23% lower risk of cardiovascular mortality (RR, 0.77; 95% CI, 0.71-0.84) and 26% lower incidence of type 2 diabetes (RR, 0.74; 95% CI, 0.72-0.77). 12 These findings were more recently confirmed by Kivim€ aki and colleagues, 13 who pooled data from 19 prospective observational cohort studies, totalling 404,840 subjects. Overall, physical inactivity was associated with 24% higher risk of coronary heart disease (hazard ratio, 1.24; 95% CI, 1.13-1.36), 16% enhanced risk of stroke (hazard ratio, 1.16; 95% CI, 1.05-1.27) and 42% higher risk of diabetes (hazard ratio, 1.42; 95% CI, 1.25-1.61).…”

Behavioural change towards reduced intensity physical activity is disproportionately prevalent among adults with serious health issues or self-perception of high risk during the UK COVID-19 lockdown

“…The extent to which adults in the UK will revert back to their usual PA regimes once lockdown measures are relaxed is unclear, but the potential for multiple lockdowns being necessary over a protracted period could lead to prolonged periods of low PA in a substantial proportion of the population. This is concerning because it is well established that insufficient levels of PA are associated with poor mental [6] and physical [7,8] health and with premature mortality [9].…”