Cognitive Decline Preceding Incident Cardiovascular Events in Older Adults.

Importance: The risk of cognitive decline and dementia following cardiovascular disease (CVD) events is well recognized. However, it remains unclear whether cognitive changes observed after such events reflect a process that begins prior to the event itself. Objective: To compare the cognitive trajectories of older adults preceding an incident CVD event with those of a matched control group without an event. Design, Setting, and Participants: Data for this nested case-control study were obtained from a prospective cohort of older, community-dwelling individuals (aged ≥65 years) in Australia and the US with no history of CVD at the time of study enrollment in the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial and the extension (ASPREE-XT) observational study. The ASPREE trial was conducted between March 2010 and December 2014, with follow-up to June 2017. The ongoing ASPREE-XT trial continued annual follow-up; this study reports data through December 2022. Case patients with an adjudicated CVD event, including fatal coronary heart disease (CHD), nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and hospitalization for heart failure (HHF), were matched by age, sex, and educational attainment to control participants without a CVD event. Data were analyzed from June to December 2024. Exposures: Cognitive function as assessed by the Modified Mini-Mental State Examination, the Hopkins Verbal Learning Test-Revised, the Symbol Digit Modalities Test, and the Controlled Oral Word Association Test. Main Outcomes and Measures: Linear mixed-effects models were used to estimate the trajectories of cognitive function among case patients with a CVD event and control participants. Results: Over 11 years, 1934 CVD events occurred among 19 114 participants. In this analysis, 1887 of 1934 case patients (97.6%) with adjudicated CVD events were matched to 7548 control participants (N = 9435; overall median age, 75.7 years [IQR, 72.4-80.0 years]; 4970 males [52.7%]). Individuals with incident CVD events had lower cognitive function, starting at between 3 and 8 years before the event, compared with those without CVD. Faster declines in global cognition (β, -0.19 [95% CI, -0.33 to -0.06]), episodic memory (β, -0.04 [-0.11 to -0.03]), processing speed (β, -0.28 [95% CI, -0.48 to -0.07]), and verbal fluency (β, -0.15 [95% CI, -0.27 to -0.04]) in the years prior to the CVD event were also observed compared with control participants. Composite global cognition (β, -0.11 [95% CI, -0.17 to -0.06]) and executive function scores (β, -0.07 [95% CI, -0.11 to -0.03]), but not memory, also declined faster. Similar cognitive trajectories were observed for fatal CHD, stroke, and HHF; however, this pattern was not observed for nonfatal MI, in which case patients and control participants showed comparable trends. Conclusions and Relevance: In this case-control study of community-dwelling older adults, deterioration in cognitive function was prominent prior to CVD events, suggesting that this decline may be associated with subsequent CVD events. These findings may help inform future research aimed at understanding the association between cognitive change and CVD.