What does this research mean for the field?

Cognitive impairment is associated with increased risks of cardiovascular death and composite cardiovascular outcomes, an association partially mediated by modifiable metabolic, lifestyle, and psychological risk factors. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

December 1, 2025BMJ OpenOpen Access

Association of cognitive impairment with adverse cardiovascular outcomes: the mediating role of modifiable risk factors in a prospective cohort study

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Why the study?

To investigate the association between cognitive impairment and CVD, quantify how uncontrolled risk factors mediate this relationship, and assess whether mediation effects vary by sex and age.

Does cognitive impairment increase the risk of cardiovascular death and composite cardiovascular outcomes in adults without prevalent CVD or dementia?

Structured PICO

Does cognitive impairment increase the risk of cardiovascular death and composite cardiovascular outcomes in adults without prevalent CVD or dementia?

Population

152,155 participants without prevalent CVD or dementia at baseline from the UK Biobank, mean age 56.3±8.2 years, 44.0% male.

Intervention

Cognitive impairment

Comparator

No cognitive impairment

Outcome

Cardiovascular death and composite cardiovascular outcomescomposite

Cognitive impairment is associated with an increased risk of cardiovascular death and composite cardiovascular outcomes, partially mediated by uncontrolled lifestyle, cardiometabolic, and psychological risk factors.

Implication

Cognitive impairment signals higher CVD risk; leaves open whether targeting mediators improves outcomes in trials.

Abstract

OBJECTIVES: To investigate, in a prospective cohort study, the association between cognitive impairment and cardiovascular disease (CVD), to quantify the extent to which uncontrolled risk factors mediate this association, and to explore whether the mediation effect varies across sex and age groups. DESIGN: Prospective cohort study. SETTING: UK Biobank, a large population-based cohort study in the UK. PARTICIPANTS: A total of 152 155 participants without prevalent CVD or dementia at baseline were included. The mean age was 56.3±8.2 years, and 44.0% were male. PRIMARY OUTCOMES: Cardiovascular death and composite cardiovascular outcomes, assessed using Cox proportional-hazards models and mediation analyses. RESULTS: During a median follow-up of 13.03-13.87 years, 1474 cardiovascular deaths and 21 518 composite cardiovascular outcomes were recorded. Participants with cognitive impairment (n=23 146; 15.2%) exhibited higher proportions of lifestyle, metabolic and psychological risks (p<0.001), except alcohol consumption. Cognitive impairment was associated with a 21% increased risk of cardiovascular death (HR 1.21, 95% CI 1.07 to 1.37) and a 5% higher risk of composite cardiovascular outcomes (HR 1.05, 95% CI 1.01 to 1.09). Mediation analyses indicated that 11.30%, 9.10% and 8.25% of the association between cognitive impairment and cardiovascular death were mediated by uncontrolled glucose, alcohol consumption and depression, respectively. Similarly, 17.50%, 12.39% and 11.98% of the association with composite cardiovascular outcomes were mediated by depression, anxiety and alcohol consumption, respectively. These mediating effects varied by sex and were more pronounced in females. CONCLUSIONS: Cognitive impairment is associated with increased risks of cardiovascular death and composite cardiovascular outcomes. Uncontrolled lifestyle, cardiometabolic and psychological risk factors partially mediate this association, highlighting the importance of comprehensive management to improve cardiovascular prognosis in this population.