Cardiovascular Health at Midlife and Alzheimer Disease Biomarkers

Background: Cardiovascular health factors are associated with cognitive decline and risk of dementia, including Alzheimer disease (AD); however, this has been mostly studied in late life. We investigated whether vascular and lifestyle factors are associated with AD plasma and imaging biomarkers in midlife. Methods: We investigated 1,406 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study with information on vascular and lifestyle factors framed from the American Heart Association (AHA) "life's essential 8" (LE8) guidelines for cardiovascular health at early midlife (mean age 45.0 ± SD 3.6) and AD biomarkers in late midlife (mean age 60 ± SD 3.5). LE8 was calculated and categorized into poor (0-49), intermediate (50-79), and ideal (80-100) cardiovascular health, based on 8 components including smoking, diet, body mass index (BMI), sleep, fasting glucose, blood pressure, cholesterol, and physical activity. We assessed the AD plasma biomarkers phosphorylated tau 217 (ptau-217) and amyloid beta 42/40 ratio (Aβ42/40) and the Spatial Pattern of Abnormality for Recognition of Early AD (SPARE-AD), an algorithm that characterizes AD-like brain atrophy on brain MRI. We used linear regression to examine the association between LE8 and log transformed and standardized AD biomarker measures adjusting for age, sex, race, education, and kidney function. Results: Compared to ideal LE8, intermediate (67.9% of participants) and poor (12.6%) LE8 was associated with lower Aβ42/40 (adjusted mean difference: -2.37, 95% CI: -2.38 to -2.36 and -2.38, 95% CI: -2.40 to -2.36, respectively). There was no association between the LE8 group and ptau-217 level. Moreover, compared to ideal LE8 participants, those with poor LE8 had higher SPARE-AD atrophy pattern (adjusted mean difference: -0.71, 95% CI: -0.81 to -0.62). Conclusion: These findings indicate that poor cardiovascular health in midlife, as defined by the AHA LE8, is linked to less favorable early AD biomarker profiles, particularly reflecting greater amyloid burden and structural brain changes.