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

Journal article
Authors Hailey A Kresge
Dandan Liu
Deepak K Gupta
Elizabeth E Moore
Katie E Osborn
Lealani Mae Y Acosta
Susan P Bell
Kimberly R Pechman
Katherine A Gifford
Lisa A Mendes
Thomas J Wang
Kaj Blennow
Henrik Zetterberg
Timothy J Hohman
Angela L Jefferson
Published in Journal of Alzheimer's disease : JAD
Volume 74
Issue 3
Pages 965-974
ISSN 1875-8908
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 965-974
Language en
Subject categories Neurochemistry


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

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