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Apolipoprotein E Genotype Modifies the Association Between Cardiac Output and Cognition in Older Adults

dc.contributor.authorBown, Corey W.
dc.contributor.authorLiu, Dandan
dc.contributor.authorOsborn, Katie E.
dc.contributor.authorGupta, Deepak K.
dc.contributor.authorMendes, Lisa A.
dc.contributor.authorPechman, Kimberly R.
dc.contributor.authorHohman, Timothy J.
dc.contributor.authorWang, Thomas J.
dc.contributor.authorGifford, Katherine A.
dc.contributor.authorJefferson, Angela L.
dc.description.abstractBackground-Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-epsilon 4 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-epsilon 4 carrier status modifies the cross-sectional association between cardiac output and cognition. Methods and Results-Vanderbilt Memory & Aging Project participants free of clinical stroke and dementia (n=306, 73 +/- 7 years, 42% female) underwent echocardiography to determine cardiac output (L/min), comprehensive neuropsychological assessment, and venous blood draw to determine APOE genotype and epsilon 4 carrier status. Linear regressions related cardiac output to neuropsychological test performance, adjusting for age, sex, education, race/ethnicity, body surface area, cognitive diagnosis, Framingham Stroke Risk Profile, and APOE-epsilon 4 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac outputxAPOE-epsilon 4 status interaction and again stratified by FA carrier status. Cardiac outputxAPOE-epsilon 4 status related to naming (beta=0.91, P=0.0009), category fluency (beta=1.2, P=0.01), information processing speed (beta=-5.4, P=0.001), visuospatial skill (beta=0.85, P=0.003), and executive function performances (beta=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-epsilon 4 carriers. Conclusions-APOE-epsilon 4 carrier status appears to modify the cross-sectional association between cardiac output and neuropsychological performance such that lower cardiac output relates to poorer performances among carriers of the epsilon 4 allele. These findings add to increasing evidence that APOE-epsilon 4 carrier status has important implications for associations between vascular and brain health in aging adults.en_US
dc.description.sponsorshipThis research was supported by T32-AG058524 (Bown), Alzheimer's Association IIRG-08-88733 (Jefferson), R01-AG034962 (Jefferson), R01-NS100980 (Jefferson), K24-AG046373 (Jefferson), Paul B. Beeson Career Development Award in Aging K23-AG045966 (Gifford), K01-AG049164 (Hohman), UL1-TR000445 (Vanderbilt Clinical Translational Science Award), and the Vanderbilt Memory & Alzheimer's Center.en_US
dc.publisherJournal of the American Heart Associationen_US
dc.rightsCopyright © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
dc.subjectAlzheimer's diseaseen_US
dc.subjectapolipoprotein E epsilon 4en_US
dc.subjectcardiac outputen_US
dc.subjectvascular risk factorsen_US
dc.titleApolipoprotein E Genotype Modifies the Association Between Cardiac Output and Cognition in Older Adultsen_US

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