Heterogeneity in the association between cardiovascular disease and cognitive decline: a pooled analysis of five...

We assessed the association between cardiovascular disease (CVD) and cognitive decline in adults aged 50 years or older using pooled data from five multinational cohorts, quantified heterogeneity, and explored its potential sources.

Individual-level data from China Health and Retirement Longitudinal Study (CHARLS), Health and Retirement Study, Survey of Health, Ageing and Retirement in Europe, English Longitudinal Study of Ageing, and Mexican Health and Aging Study (83,159 adults ≥50 years) were pooled. Linear mixed models were used to estimate CVD-cognitive decline associations, followed by random-effects meta-analysis. Heterogeneity was explored via descriptive stratification analyses, subgroup analyses, and sensitivity analyses. In supplementary analyses, we fitted time-varying CVD models, mutually adjusted models for stroke and heart disease, and separate time-varying models for stroke and heart disease as sensitivity analyses.

Substantial heterogeneity across cohorts in the association between CVD and cognitive decline (I² = 97.5%, p < 0.001) was observed. The stratification analyses revealed that CHARLS differed from the other four cohorts across multiple characteristics (region, sex, body mass index, and education). Subgroup and sensitivity analyses generally supported the main findings, although the association reversed in CHARLS when analyses were restricted to participants with CVD not taking medication. Additionally, heart disease correlated with accelerated cognitive decline across four Western cohorts, with heart disease-to-stroke ratios between 1.8:1 and 5.2:1, while stroke alone showed no significant link in any cohort.

The association between CVD and cognitive decline varies markedly across populations, with opposite directions observed between Chinese and Western cohorts. This heterogeneity may be partially explained by variations in the composition of heart disease and the use of medication across five cohorts.