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.

The authors have declared no competing interest.

The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts 75N92023D00002, 75N92023D00003, 75N92023D00004, 75N92023D00005, and 75N92023D00006 from the National Heart, Lung, and Blood Institute (NHLBI). CARDIA was also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRBs of CARDIA Field Centers (University of Alabama, Northwestern University, Kaiser Permanente Northern California, University of Minnesota) gave ethical approval of this work.

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