Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults

Abstract

Background: Left ventricular (LV) hypertrophy is associated with cerebrovascular disease and cognitive decline. Increased LV mass index is a subclinical imaging marker that precedes overt LV hypertrophy. This study relates LV mass index to white matter microstructure and cognition among older adults with normal cognition and mild cognitive impairment.

Methods and results: Vanderbilt Memory & Aging Project participants free of clinical stroke, dementia, and heart failure (n=318, 73±7 years, 58% male, 39% mild cognitive impairment) underwent brain magnetic resonance imaging, cardiac magnetic resonance, and neuropsychological assessment. Voxelwise analyses related LV mass index (g/m²) to diffusion tensor imaging metrics. Models adjusted for age, sex, education, race/ethnicity, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E-ε4 status. Secondary analyses included a LV mass index×diagnosis interaction term with follow-up models stratified by diagnosis. With identical covariates, linear regression models related LV mass index to neuropsychological performances. Increased LV mass index related to altered white matter microstructure (P<0.05). In models stratified by diagnosis, associations between LV mass index and diffusion tensor imaging were present among mild cognitive impairment participants only (P<0.05). LV mass index was related only to worse visuospatial memory performance (β=-0.003, P=0.036), an observation that would not withstand correction for multiple testing.

Conclusions: In the absence of prevalent heart failure and clinical stroke, increased LV mass index corresponds to altered white matter microstructure, particularly among older adults with clinical symptoms of prodromal dementia. Findings highlight the potential link between subclinical LV remodeling and cerebral white matter microstructure vulnerability.

Keywords: cognitive impairment; diffusion‐weighted imaging; left ventricular mass; white matter disease.

Figure 1

Participant inclusion/exclusion details. Missing data categories are mutually exclusive. Thirty‐nine total participants with LVH, CVD, or atrial fibrillation were excluded for sensitivity analyses (LVH n=10; CVD n=10; atrial fibrillation n=15; LVH and atrial fibrillation n=3; CVD and atrial fibrillation n=1). CVD indicates cardiovascular disease; DTI, diffusion tensor imaging; LV, left ventricular; LVH, left ventricular hypertrophy; MCI, mild cognitive impairment; NC, normal cognition.

Figure 2

LV mass index and mean diffusivity. Association between LV mass index and mean diffusivity. Skeletons show regions where LV mass index is positively associated with mean diffusivity in the whole sample (n=313), NC participants only (n=164), and MCI participants only (n=122). No significance was seen in the NC group. Images taken at Z=91. L indicates left; LV, left ventricular; MCI, mild cognitive impairment; NC, normal cognition; R, right.