TY - JOUR
T1 - Apolipoprotein E Genotype Modifies the Association Between Cardiac Output and Cognition in Older Adults
AU - Bown, Corey W.
AU - Liu, Dandan
AU - Osborn, Katie E.
AU - Gupta, Deepak K.
AU - Mendes, Lisa A.
AU - Pechman, Kimberly R.
AU - Hohman, Timothy J.
AU - Wang, Thomas J.
AU - Gifford, Katherine A.
AU - Jefferson, Angela L.
N1 - Funding Information:
This 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.
Publisher Copyright:
© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2019/8/6
Y1 - 2019/8/6
N2 - Background: Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-ε4 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-ε4 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 ε4 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-ε4 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac output×APOE-ε4 status interaction and again stratified by ε4 carrier status. Cardiac output×APOE-ε4 status related to naming (β=0.91, P=0.0009), category fluency (β=1.2, P=0.01), information processing speed (β=−5.4, P=0.001), visuospatial skill (β=0.85, P=0.003), and executive function performances (β=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-ε4 carriers. Conclusions: APOE-ε4 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 ε4 allele. These findings add to increasing evidence that APOE-ε4 carrier status has important implications for associations between vascular and brain health in aging adults.
AB - Background: Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-ε4 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-ε4 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 ε4 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-ε4 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac output×APOE-ε4 status interaction and again stratified by ε4 carrier status. Cardiac output×APOE-ε4 status related to naming (β=0.91, P=0.0009), category fluency (β=1.2, P=0.01), information processing speed (β=−5.4, P=0.001), visuospatial skill (β=0.85, P=0.003), and executive function performances (β=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-ε4 carriers. Conclusions: APOE-ε4 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 ε4 allele. These findings add to increasing evidence that APOE-ε4 carrier status has important implications for associations between vascular and brain health in aging adults.
KW - Alzheimer's disease
KW - apolipoprotein E ε4
KW - cardiac output
KW - cognition
KW - vascular risk factors
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U2 - 10.1161/JAHA.118.011146
DO - 10.1161/JAHA.118.011146
M3 - Article
C2 - 31364446
AN - SCOPUS:85070813729
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 15
M1 - e011146
ER -