@misc{10481/79027,
year = {2022},
month = {11},
url = {https://hdl.handle.net/10481/79027},
abstract = {Objective: The apolipoprotein E +4 (APOE +4) allele and midlife obesity are
independent risk factors for Alzheimer’s disease (AD). Both of these risk factors
are also associated with differences in brain activation, as measured by blood
oxygenation level-dependent (BOLD) responses, in the absence of detectable
cognitive deficits. Although the presence of these risk factors may influence
brain activity during working memory tasks, no study to date has examined
whether the presence of the +4 allele explains variation in working memory
brain activity while matching for levels of overweight/obesity. The primary
aim of this study was to determine whether the presence of the +4 allele is
associated with differences in task-functional magnetic resonance imaging
(fMRI) brain activation in adults with overweight/obesity. We predicted that +4
carriers would have greater brain activation in regions that support working
memory.
Methods: This ancillary study included 48 (n = 24 APOE +4 carriers;
n = 24 APOE +4 non-carriers), sedentary middle-aged adults
(Mean age = 44.63   8.36 years) with overweight/obesity (Mean
BMI = 32.43   4.12 kg/m2) who were matched on demographic
characteristics. Participants were a subsample enrolled in 12-month
randomized clinical trial examining the impact of energy-restricted diet
and exercise on cardiovascular health outcomes. Participants completed
a n-back working memory task with fMRI, which were completed within
one month of the start of the intervention. Participants also underwent
pseudo-continuous arterial spin labeling scans, a MRI measure of cerebral
blood flow (CBF). Results: Compared to non-+4 carriers with overweight/obesity, +4 carriers
with overweight/obesity had lower fMRI brain activity in the middle frontal
gyrus, pre and post central gyrus, supramarginal gyrus, superior temporal
gyrus, lateral occipital cortex, and angular gyrus (z range = 2.52–3.56) during
the n-back working memory task. Differences persisted even when controlling
for CBF in these brain regions.
Conclusion: These results indicate that presence of the APOE +4 allele in
middle-aged adults with overweight/obesity is related to altered brain activity
during a working memory paradigm, which may confer risk for accelerated
neurocognitive decline in late adulthood. Future research is needed to clarify
the clinical implications of these findings in the context of risk for AD.},
organization = {United States Department of Health & Human Services},
organization = {National Institutes of Health (NIH) - USA		
University of Pittsburgh Clinical and Translational Science Institute (CTSI)	3R01AG060741-03S1	
R01 DK095172	
R01-HL103646	
UL1 TR001857},
publisher = {Frontiers},
keywords = {APOE},
keywords = {fMRI},
keywords = {Cerebral blood flow (CBF)},
keywords = {Obesity},
keywords = {Working memory},
title = {Reduced brain activity during a working memory task in middle-aged apolipoprotein E +4 carriers with overweight/obesity},
doi = {10.3389/fnhum.2022.1001229},
author = {Drake, Jermon A. and Erickson, Kirk I.},
}