Researchers tracking initially healthy older adults found that declines in thinking speed and other cognitive abilities can appear years before cardiovascular disease becomes clinically evident, pointing to a possible early warning window for prevention.
Study: Cognitive Decline Preceding Incident Cardiovascular Events in Older Adults. Image Credit: Vitalii Vodolazskyi / Shutterstock
A recent study published in JAMA Network Open suggests that cognitive decline may begin years before a cardiovascular disease (CVD) event. Researchers analyzed 11-year data from initially healthy older adults in the Aspirin in Reducing Events in the Elderly (ASPREE) and its extension.
The analysis showed that individuals who developed CVD experienced faster declines across multiple cognitive domains than controls. Notably, processing speed showed measurable deterioration as early as eight years prior, highlighting its potential as an early indicator of future CVD risk and the value of cognitive monitoring.
CVD and dementia often coexist in older adults, reflecting a complex, bidirectional interplay between cardiac and brain health. While considerable evidence shows that cognitive decline follows CVD events, particularly stroke, the timing and origin of these changes remain uncertain.
Researchers have not established whether cognitive deterioration begins before the event or results from its acute effects. Although some studies link poorer cognitive function to higher CVD risk, findings on pre-event cognitive trajectories are inconsistent and limited by small event numbers, reliance on self-reported outcomes, and a lack of domain-specific analyses, leaving a critical gap in understanding when cognitive decline truly begins.
ASPREE Cognitive Trajectory Study Design
In the present study, researchers examined whether cognitive decline precedes incident CVD events in older adults.
The team drew participants mainly aged 70 years and older, with eligibility from age 65 years for racial and ethnic minority individuals in the United States, from the ASPREE study and its ongoing extension, the ASPREE-XT trial.
These studies included individuals from the United States and Australia who were free of prior CVD at enrollment. The ASPREE study, conducted between 2010 and 2014, followed participants through 2017, while ASPREE-XT provided annual follow-ups through December 2022.
The investigators identified cases as participants who experienced incident CVD events, including hospitalization for heart failure (HHF), nonfatal myocardial infarction (MI), stroke, or fatal coronary heart disease (CHD).
They confirmed events using hospital records, physician reports, death certificates, and family input, with adjudication by expert panels. For comparison, they matched each case to four control individuals without CVD events based on age, sex, and education.
The authors assessed cognitive function using standardized tests targeting specific domains. These included the Modified Mini-Mental State Examination (3MS) for global cognition, the Symbol Digit Modalities Test (SDMT) for processing speed, the Controlled Oral Word Association Test (COWAT) for verbal fluency, and the Hopkins Verbal Learning Test–Revised (HVLT-R) for episodic memory.
The researchers applied mixed-effects statistical models to assess cognitive trajectories in cases and controls. Subgroup analyses further examined differences by sex and baseline comorbidity status.
Processing Speed and Pre-CVD Cognitive Decline
Over a median follow-up of 8.7 years, the study recorded 1,934 incident CVD events among 19,114 participants, of which 1,887 cases were successfully matched to 7,548 controls. Participants had a median age of 76 years, and just over half were men.
Individuals who experienced a CVD event had significantly faster cognitive decline across multiple domains compared to controls, with changes emerging three to eight years before CVD onset.
Declines in processing speed appeared first, up to 8 years before onset, followed by changes in episodic memory and global cognition around 5 years before onset, with verbal fluency affected approximately 3 years before onset.
Composite measures of executive function and global cognition also showed accelerated decline beginning about six years prior to CVD onset, while the composite memory trajectory did not differ significantly between groups.
These patterns were consistent across most CVD subtypes, including stroke, heart failure, and fatal coronary heart disease, but were less pronounced for nonfatal myocardial infarction.
Sex-stratified and subgroup analyses by diabetes, chronic kidney disease, and hypertension mirrored the primary results, although some trajectories were steeper in females and effect sizes were slightly larger in participants with chronic conditions.
These findings suggest that cognitive decline may reflect shared vascular and neurological processes that precede overt cardiovascular events. Chronic exposure to risk factors such as hypertension and smoking may help explain microvascular and endothelial dysfunction, impaired cerebral perfusion, and accelerated cognitive deterioration.
The weaker association observed for nonfatal myocardial infarction may indicate differing underlying mechanisms or a lower burden of preclinical disease in these individuals, although the study did not directly test these mechanisms.
Cognitive Monitoring and Cardiovascular Prevention
The findings indicate that cognitive decline, particularly in processing speed, can emerge several years preceding the onset of cardiovascular disease, suggesting potential value for early risk detection.
Incorporating routine cognitive assessments into preventive care may help identify high-risk individuals and improve risk stratification, although meaningful thresholds for decline remain to be established.
Such assessments would more likely serve as complementary markers of vascular health rather than diagnostic tools at this stage. The variation in cognitive trajectories across CVD subtypes further suggests distinct underlying mechanisms, with chronic vascular and neurovascular dysfunction potentially contributing to early decline in conditions such as stroke and heart failure.
Future research should adopt a life-course perspective and include diverse populations to better understand these associations. Integrating biomarker-based measures of subclinical vascular disease, such as arterial stiffness, inflammation, and neurovascular imaging, may clarify the link between early cognitive changes and subsequent CVD, informing more targeted prevention strategies.
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