Cardiac Output Tied to Brain Volume in APOE-ε4 Carriers

TOPLINELower cardiac output was associated with a smaller brain volume in older adults carrying the apolipoprotein E (APOE)-ε4 allele, but not in non-carriers, a study found.METHODOLOGYResearchers conducted a cohort study using data from the Vanderbilt Memory and Aging Project, which enrolled older adults aged 50-92 years without dementia at baseline.A total of 756 adults (mean age, 67 years; 47% men; 81% White non-Hispanic individuals) were included, comprising 488 APOE-ε4 non-carriers and 268 APOE-ε4 carriers, with follow-up averaging 4.7 years.Cardiac output was measured at baseline using echocardiography, and brain MRI was performed longitudinally to assess gray matter volumes in multiple regions including the total brain, frontal lobe, temporal lobe, parietal lobe, occipital lobe, hippocampus, inferior lateral ventricle, and Alzheimer's disease signature regions.Associations between baseline cardiac output and longitudinal gray matter volume changes were examined, adjusting for age, sex, race/ethnicity, education, body surface area, cognitive status, Framingham Stroke Risk Profile score, and intracranial volume, with interaction terms testing whether APOE-ε4 status modified these associations.TAKEAWAYIn cross-sectional analysis, cardiac output was not associated with gray matter volume and did not interact with APOE-ε4 status or cognitive status on gray matter volume. In stratified analysis, among APOE-ε4 carriers, lower cardiac output was associated with smaller total brain (β = 5768 mm; P = .02), temporal lobe (β = 1184 mm³; P = .02), and occipital lobe (β = 884 mm³; P = .02).In non-carriers, cardiac output was not significantly associated with longitudinal changes in any gray matter region examined.In longitudinal analysis, baseline cardiac output interacted with APOE-ε4 status on the inferior lateral ventricle (β = −30.5 mm³; P = .006). Lower heart rate was associated with larger inferior lateral ventricle volume over time in APOE-ε4 carriers (β = -3.5, P = .04), but stroke volume was not.IN PRACTICE"Lower cardiac output at baseline is associated with small brain volumes over time in the medial temporal lobes in participants who are APOE-ε4 carriers. Results suggest that subclinical cardiac dysfunction may be a key risk factor for future neurodegeneration in individuals with a genetic predisposition to Alzheimer’s disease," the authors wrote."Screening of cardiovascular function, even in middle age, may be a useful tool for risk quantification among individuals who are APOE-ε4 carriers," they added.SOURCEThe study was led by Elizabeth E. Moore, Mass General Brigham, Boston. It was published online on August 4 in Alzheimer's & Dementia.LIMITATIONSThe cohort was predominantly White, well-educated, and relatively healthy, limiting generalizability to other races, ethnicities, and populations with greater vascular risk or cardiovascular disease burden. Cardiac output was measured at a single timepoint, which may not fully reflect resting cardiac function due to acute metabolic fluctuations. Some findings did not survive correction for multiple comparisons, and some significant interaction results did not yield significant stratified results, requiring cautious interpretation.DISCLOSURESThe study was funded by the Alzheimer's Association, the Richard Eugene Hickman Alzheimer’s Disease Research Endowment, and the Vanderbilt Memory and Alzheimer’s Center. Some authors reported having employment ties with various organizations. Detailed disclosures are provided in the original article.This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.