Cardiorespiratory Fitness, Coronary Artery Calcium, and Risk of Later-Life Dementia: The Cooper Center Longitudinal Study.

BACKGROUND: Cardiorespiratory fitness (CRF) and coronary artery calcium (CAC) are established cardiovascular risk markers reflecting physiological reserve and subclinical atherosclerosis, respectively. Their independent and joint associations with dementia remain unclear. OBJECTIVES: We examined mid-to-late midlife CRF and CAC in relation to later-life dementia within a large U.S. METHODS: Participants in the Cooper Center Longitudinal Study (1998-2018) were linked to Medicare claims (1999-2019). CRF was estimated via maximal treadmill testing (categorized as age- and sex-specific low, moderate, or high); CAC was categorized as <100 vs ≥100 Agatston units. Incident all-cause dementia was identified via Medicare surveillance. Parametric illness-death models estimated HRs for dementia, accounting for competing mortality and adjusting for demographic, behavioral, and cardiometabolic risk factors, with mutual adjustment for CRF and CAC. RESULTS: Among 10,933 participants free of cardiovascular disease and dementia at baseline (mean age 57.2 years; 30.2% women), 868 dementia cases occurred over a median follow-up of 5.8 years. After multivariable adjustment, high CRF (vs low) was associated with a lower dementia risk (HR: 0.69; 95% CI: 0.53-0.90), whereas CAC ≥100 (vs <100) was associated with a higher risk (HR: 1.24; 95% CI: 1.07-1.44). Continuous analyses demonstrated a linear inverse association for CRF and a graded positive association for CAC. No interaction between CRF and CAC was observed. CONCLUSIONS: Lower CRF and higher CAC are independently associated with incident dementia. These findings support complementary, nonoverlapping roles of functional fitness and cumulative vascular injury in dementia pathogenesis, highlighting the importance of lifelong cardiovascular health.