What is the clinical evidence from this study?

Study design: Case-Control. Population: Incident cardiovascular events (n=9435). Intervention: Incident CVD event vs. Matched controls without CVD event. Primary outcome: Trajectories of cognitive function (β -0.19, 95% CI -0.33 to -0.06).

What question did this study set out to answer?

To compare cognitive trajectories of older adults before a cardiovascular event to those without such events.

April 22, 2026Open Access

Cognitive Decline Preceding Incident Cardiovascular Events in Older Adults

Key Result

Individuals with incident CVD events experienced faster declines in global cognition (β, -0.19; 95% CI, -0.33 to -0.06) starting 3 to 8 years before the event compared with matched controls.

Key Points

To compare cognitive trajectories of older adults before a cardiovascular event to those without such events.
Nested case-control study using data from the ASPREE trial and ASPREE-XT study.
Assessed cognitive function using multiple tests such as the Modified Mini-Mental State Examination and Hopkins Verbal Learning Test.
Data analyzed from 19114 participants between June and December 2024.
1934 CVD events observed among 19114 participants over 11 years.
Cognitive declines noted 3 to 8 years before CVD events, including global cognition (β, −0.19), episodic memory (β, −0.04), and processing speed (β, −0.28), all with significant CI.
Similar trends for cognitive decline were observed in cases of fatal CHD, stroke, and heart failure, but not in nonfatal myocardial infarction.

Study Design

Type

Case-Control (n=9,435)

Multicenter

Yes

Structured PICO

Does cognitive decline precede incident cardiovascular events in older adults?

Population

9,435 older, community-dwelling individuals (aged ≥65 years) with no history of CVD at enrollment, including 1,887 case patients with an adjudicated incident CVD event and 7,548 matched controls. Overall median age 75.7 years, 52.7% male.

Intervention

Incident cardiovascular disease (CVD) event (fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, and hospitalization for heart failure)

Comparator

Matched control participants without a CVD event (matched by age, sex, and educational attainment)

Outcome

Trajectories of cognitive function (assessed by Modified Mini-Mental State Examination, Hopkins Verbal Learning Test–Revised, Symbol Digit Modalities Test, and Controlled Oral Word Association Test) preceding the eventsurrogate

Deterioration in cognitive function precedes incident cardiovascular events by 3 to 8 years in older adults, suggesting cognitive decline may be an early marker of subsequent CVD risk.

Main Result

Effect estimate: β -0.19 (95% CI -0.33 to -0.06)

Abstract

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.