Lower cardiac output is a risk factor for faster cerebral atrophy over a 11-year follow-up period in APOE-ε4 carriers
Published in Alzheimer's & Dementia, 2026
Recommended citation: Moore, E. E., Zhang, P., Khan, O. A., Liu, D., Gupta, D. K., Pechman, K. R., Gifford, K. A., Landman, B. A., Hohman, T. J. and Jefferson, A. L. (2026). "Lower cardiac output is a risk factor for faster cerebral atrophy over a 11-year follow-up period in APOE-ε4 carriers." Alzheimer's & Dementia, 22(8), e71598. https://doi.org/10.1002/alz.71598
Introduction
This study examined whether subtle reductions in cardiac output were associated with brain atrophy and whether associations differed by APOE-ε4 status.
Methods
The Vanderbilt Memory and Aging Project included 756 adults aged 50-92 years. Baseline echocardiography measured cardiac output, and serial MRI assessed brain volumes over up to 11 years (mean follow-up: 4.7 years). Adjusted regression models examined baseline associations and longitudinal changes.
Results
Among APOE-ε4 carriers, lower cardiac output was associated with smaller brain volumes at baseline and greater enlargement of the inferior lateral ventricles over time. These associations were absent in non-carriers.
Discussion
Subclinical cardiac dysfunction may contribute to neurodegeneration in genetically susceptible adults. Replication is needed, particularly because many findings did not survive correction for multiple comparisons.
Highlights
- Cardiac output and brain structure were studied over up to 11 years.
- Associations differed by APOE-ε4 carrier status.
- Longitudinal findings implicated the medial temporal region.
- Findings warrant cautious interpretation and independent replication.