Cardiac function and neuropathological substrates on MRI across age span: A Cross‐Cohort Collaboration (CCC)

Abstract

AbstractBackgroundCardiac dysfunction has been linked to an increased risk of dementia. However, the underlying pathophysiological substrates remain largely unspecified due to considerable heterogeneity in prior studies. We aggregated data from seven community‐based studies within the Cross‐Cohort Collaboration, to study the association between cardiac function and brain health.MethodsParticipants from all cohorts underwent echocardiography to assess systolic function (left ventricular ejection fraction (LVEF)) and diastolic function (EA‐ratio, deceleration time (DT)). High‐resolution brain MRI was performed to compute volumes of total brain (TBV), gray matter, white matter, hippocampus, and white matter hyperintensities (WMH). We used multivariable linear regression models to determine the association of echocardiographic measures and clinical heart failure with brain volumes, pooling the results using random‐effects meta‐analysis.ResultsAmong 10,307 individuals (median age: 62.5 years [54.7 – 70.5]; 54.9% women), moderate to severe systolic function was associated with lower total brain volume (beta per 1‐SD decrease: ‐0.18; 95%CI [‐0.32 ‐ ‐0.04], I2=36%), most profound for white matter and hippocampal volumes. Impaired relaxation in the diastolic phase was associated with smaller total brain volumes (‐0.10; 95%CI [‐0.16 ‐ ‐0.04], I2=2%), again driven by white matter and the hippocampi. Restrictive diastolic function similarly predisposed to lower hippocampal volume (‐0.16; 95%CI [‐0.31 ‐ ‐0.01], I2=0%). Diastolic dysfunction, but not systolic function, was associated with higher volume of WMH (0.03; 95%CI [0.01‐0.05]; I2=0% for DT). Of 8055 participants with clinical data, 277 (3.4%) had heart failure, which was related to all lower brain volumes. These results were consistent across cohorts. In stratified analyses, higher LVEF was associated with higher TBV, from age 50‐59 years onwards up until the oldest age category (80+ years), including larger hippocampi (0.04; 95%CI [0.00‐0.08]; I2=0%) for those aged between 50‐59 years.ConclusionCardiac dysfunction is associated with brain imaging markers of neurodegeneration in community‐dwelling individuals from midlife to late‐life. Preservation of cardiac function may be an additional target to promote cognitively healthy ageing.