The Vanderbilt Memory and Aging Project followed 756 adults aged 50–92 years (mean 67 ± 9 years) for up to 11 years (mean 4.7 years) to examine whether baseline cardiac output related to cross-sectional and longitudinal gray matter volumes, and whether APOE-ε4 status modified these associations.
Lower baseline cardiac output was linked to smaller total brain, temporal lobe, and occipital lobe volumes cross-sectionally in APOE-ε4 carriers only (p < 0.04). Longitudinally, cardiac output interacted with APOE-ε4 status on inferior lateral ventricle volume (p = 0.006), with lower cardiac output predicting greater ventricular expansion (a proxy for medial temporal atrophy) only in APOE-ε4 carriers (p = 0.01). No associations were found in APOE-ε4 non-carriers.
- Predominantly White, well-educated, healthy cohort limits generalizability. - Cardiac output measured at a single time point, which may not reflect habitual resting function. - Many findings did not survive false discovery rate correction, and significant interaction terms did not always yield significant stratified results—and vice versa.
In patients who carry the APOE-ε4 allele, even subclinical reductions in cardiac output may accelerate brain atrophy, especially in the medial temporal lobe. Consider cardiac screening as part of dementia-risk evaluation in APOE-ε4 carriers, while awaiting replication in more diverse cohorts.
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