Effect of Alzheimer Disease Risk on Brain Function During Self-appraisal in Healthy Middle-aged Adults

Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705, USA.
Archives of General Psychiatry (Impact Factor: 14.48). 11/2007; 64(10):1163-71. DOI: 10.1001/archpsyc.64.10.1163
Source: PubMed


Asymptomatic middle-aged adult children of patients with Alzheimer disease (AD) recently were found to exhibit functional magnetic resonance imaging (fMRI) deficits in the mesial temporal lobe during an encoding task. Whether this effect will be observed on other fMRI tasks is yet unknown. This study examines the neural substrates of self-appraisal (SA) in persons at risk for AD. Accurate appraisal of deficits is a problem for many patients with AD, and prior fMRI studies of healthy young adults indicate that brain areas vulnerable to AD such as the anterior mesial temporal lobe and posterior cingulate are involved during SA tasks.
To determine whether parental family history of AD (hereafter referred to as FH) or presence of the epsilon4 allele of the apolipoprotein E gene (APOE4) exerts independent effects on brain function during SA.
Cross-sectional factorial design in which APOE4 status (present vs absent) was one factor and FH was the other. All participants received cognitive testing, genotyping, and an fMRI task that required subjective SA decisions regarding trait adjective words in comparison with semantic decisions about the same words.
An academic medical center with a research-dedicated 3.0-T MR imaging facility.
Cognitively normal middle-aged adults (n = 110), 51 with an FH and 59 without an FH.
Blood oxygen-dependent contrast measured using T2*-weighted echo-planar imaging.
Parental family history of AD and APOE4 status interacted in the posterior cingulate and left superior and medial frontal regions. There were main effects of FH (FH negative > FH positive) in the left hippocampus and ventral posterior cingulate. There were no main effects of APOE genotype.
Our results suggest that FH may affect brain function during subjective SA in regions commonly affected by AD. Although the participants in this study were asymptomatic and middle-aged, the findings suggest that there may be subtle alterations in brain function attributable to AD risk factors.

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Available from: Carey Gleason, Aug 28, 2014
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    • "There were also studies reviewed which did not support the existence of a compensatory recruitment process in older cognitively intact ε4 carriers. Johnson et al. [54] found that APOE genotype alone did not impact neural activity during a self-appraisal task in middle-age adults, although APOE status did interact with a family history of AD to produce greater frontal and posterior cingulate activations in ε4 carriers without a family history of AD. Johnson et al. [55] reported similar results in an earlier study of middle-age adults using an episodic memory task. While APOE ε4 carriers with no family history of AD did show the predicted enhanced recruitment of MTL structures, ε4 carriers with a family history of AD actually showed the lowest levels of MTL recruitment of all participant groups [55]. "
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