Lower cardiac output is associated with neurodegeneration among older adults with normal cognition but not mild cognitive impairment

Subclinical cardiac dysfunction is associated with smaller total brain volume on magnetic resonance imaging (MRI). To study whether cardiac output relates to regional measurements of grey and white matter structure, older adults (n=326) underwent echocardiogram to quantify cardiac output (L/min) and brain MRI. Linear regressions related cardiac output to grey matter volumes measured on T(1) and white matter hyperintensities assessed on T(2)-FLAIR. Voxelwise analyses related cardiac output to diffusion tensor imaging adjusting for demographic, genetic, and vascular risk factors. Follow-up models assessed a cardiac output x diagnosis interaction with stratification (normal cognition, mild cognitive impairment). Cardiac output interacted with diagnosis, such that lower cardiac output related to smaller total grey matter (p=0.01), frontal lobe (p=0.01), and occipital lobe volumes (p=0.01) among participants with normal cognition. When excluding participants with cardiovascular disease and atrial fibrillation, associations emerged with smaller parietal lobe (p=0.005) and hippocampal volume (p=0.05). Subtle age-related cardiac changes may contribute to disrupt neuronal homeostasis and impact grey matter integrity prior to cognitive impairment.