Lower Left Ventricular Ejection Fraction Relates to Cerebrospinal Fluid Biomarker Evidence of Neurodegeneration in Older Adults

Abstract

Background:

Subclinical cardiac dysfunction is associated with decreased cerebral blood flow, placing the aging brain at risk for Alzheimer’s disease (AD) pathology and neurodegeneration.

Objective:

This study investigates the association between subclinical cardiac dysfunction, measured by left ventricular ejection fraction (LVEF), and cerebrospinal fluid (CSF) biomarkers of AD and neurodegeneration.

Methods:

Vanderbilt Memory & Aging Project participants free of dementia, stroke, and heart failure (n = 152, 72±6 years, 68% male) underwent echocardiogram to quantify LVEF and lumbar puncture to measure CSF levels of amyloid-β₄₂ (Aβ₄₂), phosphorylated tau (p-tau), and total tau (t-tau). Linear regressions related LVEF to CSF biomarkers, adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E ɛ4 status. Secondary models tested an LVEF x cognitive diagnosis interaction and then stratified by diagnosis (normal cognition (NC), mild cognitive impairment (MCI)).

Results:

Higher LVEF related to decreased CSF Aβ₄₂ levels (β= –6.50, p = 0.04) reflecting greater cerebral amyloid accumulation, but this counterintuitive result was attenuated after excluding participants with cardiovascular disease and atrial fibrillation (p = 0.07). We observed an interaction between LVEF and cognitive diagnosis on CSF t-tau (p = 0.004) and p-tau levels (p = 0.002), whereas lower LVEF was associated with increased CSF t-tau (β= –9.74, p = 0.01) and p-tau in the NC (β= –1.41, p = 0.003) but not MCI participants (p-values>0.13).

Conclusions:

Among cognitively normal older adults, subclinically lower LVEF relates to greater molecular evidence of tau phosphorylation and neurodegeneration. Modest age-related changes in cardiovascular function may have implications for pathophysiological changes in the brain later in life.