Abstract
BACKGROUND AND OBJECTIVES: Cardiac dysfunction and heart failure are linked to cognitive impairment, but the underlying brain pathology remains undetermined. We investigated associations between cardiac function (measured by echocardiography or cardiac MRI), clinical heart failure, and structural markers on brain MRI, including volumes of gray and white matter (WM), the hippocampus, and white matter hyperintensities (WMHs). METHODS: We leverage data from 7 prospective, community-based cohorts across Europe and the United States, all part of the Cross-Cohort Collaboration. The included cohorts were the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in Communities study, Austrian Stroke Prevention Study, Cardiovascular Health Study, Framingham Heart Study, Rotterdam Study, and Study of Health in Pomerania (SHIP-START and SHIP-TREND). Each cohort performed cross-sectional multivariable linear regression analyses, after which estimates were pooled through random-effects meta-analysis. Heterogeneity was assessed by the I(2) index (%). RESULTS: Among 10,889 participants (mean age: 66.8 years, range 52.0-76.0; 56.7% women), markers of systolic dysfunction were consistently associated with smaller total brain volume (TBV) (e.g., adjusted standardized mean difference for moderate to severe dysfunction -0.19, 95% CI -0.31 to -0.07, I(2) = 20%). Impaired relaxation and restrictive diastolic dysfunction were also associated with smaller TBV (e.g., for impaired relaxation -0.08, 95% CI -0.15 to -0.01, I(2) = 32%) and hippocampal volume (-0.18, 95% CI -0.33 to -0.03, I(2) = 0%), with similar results for the E/A-ratio. Systolic and diastolic dysfunction was not consistently associated with volume of WMHs. Among 5 cohorts with available data, 302 (3.4%) participants had clinical heart failure, which was associated with smaller brain volumes, particularly in the hippocampus (-0.13, 95% CI -0.23 to -0.02, I(2) = 1%). DISCUSSION: In this large study among community-dwelling adults, subclinical cardiac dysfunction was associated with brain imaging markers of neurodegeneration. These findings encourage longitudinal investigations on the effect of maintaining cardiac function on brain health.