Reduced brain activity during a working memory task in middle-aged apolipoprotein E ε4 carriers with...

Area of Science:

• Neuroscience
• Genetics
• Public Health

Background:

• Midlife obesity and the apolipoprotein E ε4 (APOE ε4) allele are known risk factors for Alzheimer's disease (AD).
• Both factors are associated with altered brain activation (BOLD responses) even without cognitive impairment.
• Previous research has not specifically examined APOE ε4's impact on working memory brain activity in overweight/obese individuals.

Purpose of the Study:

• To investigate if the APOE ε4 allele is associated with differences in task-functional magnetic resonance imaging (fMRI) brain activation.
• To determine these associations in middle-aged adults with overweight/obesity during a working memory task.

Main Methods:

• Included 48 middle-aged adults (mean age 44.63) with overweight/obesity (mean BMI 32.43), matched demographically.
• Participants were divided into APOE ε4 carriers (n=24) and non-carriers (n=24).
• A n-back working memory task using fMRI and arterial spin labeling (ASL) for cerebral blood flow (CBF) was administered.

Main Results:

• APOE ε4 carriers exhibited lower fMRI brain activity in several regions, including the middle frontal gyrus and lateral occipital cortex, during the working memory task compared to non-carriers.
• These differences in brain activation persisted even after controlling for cerebral blood flow.
• Regions showing reduced activity included the pre and post central gyrus, supramarginal gyrus, superior temporal gyrus, and angular gyrus.

Conclusions:

• The presence of the APOE ε4 allele in middle-aged adults with overweight/obesity is associated with altered brain activity during working memory.
• These alterations may indicate an increased risk for accelerated neurocognitive decline and Alzheimer's disease.
• Further research is required to fully understand the clinical implications of these findings for AD risk.