What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Cardiovascular disease and cognitive decline (n=83159). Intervention: Cardiovascular disease (CVD) vs. Non-CVD. Primary outcome: Annual rate of cognitive decline (standardized Z-scores) (β -0.0207, 95% CI -0.08 to 0.04, p=0.3887).

What does this research mean for the field?

Cardiovascular disease is not significantly associated with overall cognitive decline across pooled global populations, demonstrating marked international heterogeneity with accelerated decline in Western cohorts and an inverse association in a Chinese cohort. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

September 1, 2026Alzheimer s & DementiaOpen Access

Heterogeneity in the association between cardiovascular disease and cognitive decline: a pooled analysis of five prospective cohort studies from 24 countries

Q: What are the key findings of this study?

Cardiovascular disease was not significantly associated with overall cognitive decline in the pooled analysis (β -0.0207), though substantial heterogeneity was observed across populations with accelerated decline in Western cohorts and a protective trend in the Chinese cohort.

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Key result

Pre-existing CVD shows no overall association with accelerated cognitive decline in pooled analysis.

β -0.0207
95% CI -0.08 to 0.04
P=0.3887
n=83,159

Why the study?

The association between cardiovascular disease and cognitive decline in adults aged 50 years or older varies across populations and remains incompletely understood, with heterogeneity and its sources not fully characterized.

Does cardiovascular disease accelerate cognitive decline in adults aged 50 years or older?

Study Design

Type

Meta-Analysis (n=83,159)

Multicenter

Yes

Structured PICO

Does cardiovascular disease accelerate cognitive decline in adults aged 50 years or older?

Population

83,159 adults aged 50 years or older across five prospective longitudinal cohorts in 24 countries, followed for a median of 4 to 9 years to assess the association between cardiovascular disease and cognitive decline.

Exposure

Pre-existing Cardiovascular Disease (CVD), defined as self-reported physician diagnosis of heart disease (e.g., myocardial infarction, coronary heart disease, angina, congestive heart failure), stroke, or current use of prescribed medication for these conditions.

Comparator

Participants without cardiovascular disease (non-CVD group).

Outcome

Annual rate of cognitive decline (assessed via standardized global cognitive function Z-scores derived from memory, numeracy, and orientation domains).

Main Result

Standardized Mean Difference: -0.0207 (95% CI -0.08–0.04)

p-value: p=0.3887

The association between cardiovascular disease and cognitive decline is highly heterogeneous across populations, significantly accelerating cognitive decline in Western cohorts but showing opposite or null effects in Chinese and Mexican cohorts.

Limitations

CVD status primarily relied on self-reported physician diagnoses, introducing potential exposure misclassification.
Inconsistent data on CVD onset precluded pre- and post-diagnosis trajectory analyses, potentially introducing survivor bias.
Cause-specific reasons for loss to follow-up were not consistently available across all harmonized cohorts.
Harmonization cannot completely remove cross-cultural differences in cognitive test results, self-reported health, and healthcare access.
Absence of comprehensive clinical data regarding CVD treatment and severity across cohorts.
Datasets lacked data on transient ischemic attacks (TIAs).
Possibility of residual reverse causality due to the observational nature of the cohorts.
Treatment of CVD as a unified entity, whereas the true association is likely concentrated in heart disease.
Differential loss to follow-up (higher attrition rates among those with CVD across all cohorts)
Significant exclusions due to missing baseline data (ranging from 9.6% in HRS to 63.6% in CHARLS)
Use of self-reported physician diagnosis and medication use to define CVD status

Implication

Heterogeneity across populations cautions against broad clinical inferences; leaves open ethnicity-specific effects for prospective validation.

Abstract

INTRODUCTION: 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. METHODS: 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. RESULTS: = 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. DISCUSSION: 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.

Discussion

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Published by Alzheimer s & Dementia · CC BY-NC-ND

Cite This Study

Li et al. (2026) conducted a meta-analysis in Cardiovascular disease and cognitive decline (n=83,159). Cardiovascular disease (CVD) vs. Non-CVD was evaluated on Annual rate of cognitive decline (standardized Z-scores) (β -0.0207, 95% CI -0.08 to 0.04, p=0.3887). Cardiovascular disease was not significantly associated with overall cognitive decline in the pooled analysis (β -0.0207), though substantial heterogeneity was observed across populations with accelerated decline in Western cohorts and a protective trend in the Chinese cohort.

synapsesocial.com/papers/6ac5b7ae6f3cfd46c823b203 https://doi.org/10.1002/alz.71843

Topics

Women and heart disease

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Implication

Heterogeneity across populations cautions against broad clinical inferences; leaves open ethnicity-specific effects for prospective validation.

Heterogeneity in the association between cardiovascular disease and cognitive decline: a pooled analysis of five prospective cohort studies from 24 countries

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

Topics

Heterogeneity in the association between cardiovascular disease and cognitive decline: a pooled analysis of five prospective cohort studies from 24 countries

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

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