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: 13.75). 11/2007; 64(10):1163-71. DOI: 10.1001/archpsyc.64.10.1163
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Carey Gleason, Aug 28, 2014
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: How and when the known genetic risk allele, apolipoprotein E-epsilon4 (APOEepsilon4), confers risk to Alzheimer's disease has yet to be determined. We studied older adults and found that APOEepsilon4 carriers had greater neural activation in the medial frontal and parahippocampal gyrus during a memory task (cluster-corrected p < .01). When compared to a group of younger adults, interactive effects of age and APOEepsilon4 were found in the inferior frontal-anterior temporal region, one of the first areas to develop amyloid plaques in patients with Alzheimer's disease, and, in the posterior cingulate, one of the earliest areas to show decreased cerebral metabolism in Alzheimer's disease. Thus, abnormally high activation in fronto-temporal areas are present in both younger and older APOEepsilon4 carriers confronted with a working memory task when compared to non-APOEepsilon4 carriers. This effect, however, appears to diminish with age.
    Brain Imaging and Behavior 06/2010; 4(2):177-88. DOI:10.1007/s11682-010-9097-9 · 3.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Structural brain change and concomitant cognitive decline are the seemingly unavoidable escorts of aging. Despite accumulating studies detailing the effects of age on the brain and cognition, the relationship between white matter features and cognitive function in aging have only recently received attention and remain incompletely understood. White matter microstructure can be measured with diffusion tensor imaging (DTI), but whether DTI can provide unique information on brain aging that is not explained by white matter volume is not known. In the current study, the relationship between white matter microstructure, age, and neuropsychological function was assessed using DTI in a statistical framework that employed white matter volume as a voxel-wise covariate in a sample of 120 healthy adults across a broad age range (18-83). Memory function and executive function were modestly correlated with the DTI measures while processing speed showed the greatest extent of correlation. The results suggest that age-related white matter alterations underlie age-related declines in cognitive function. Mean diffusivity and fractional anisotropy in several white matter brain regions exhibited a nonlinear relationship with age, while white matter volume showed a primarily linear relationship with age. The complex relationships between cognition, white matter microstructure, and white matter volume still require further investigation.
    Developmental Neuropsychology 05/2010; 35(3):257-77. DOI:10.1080/87565641003696775 · 2.67 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent neuroimaging work has observed activity in cortical midline structures (CMS) such as medial prefrontal and posterior cingulate cortices during self-referential processing. Moreover, items rated as self-relevant produce increased activity in these regions relative to items that are deemed not self-relevant. A common thread among previous reports has been reliance on experimental tasks that encourage or require online self-referential processing. In this paper, we report findings from two experiments that manipulated requirements for self-reflection. In Experiment 1, subjects rated trait adjectives for social desirability and for self-relevance. Results revealed increasing activity in CMS with increasing self-relevance, but only during explicit ratings of self-relevance. In Experiment 2, we examined CMS activity during passive viewing of personal semantic facts (such as subjects' own first names). Taken together, these results suggest that highly self-relevant information captures attention through neural mechanisms that are comparable to those engaged during explicit self-reflection, namely via recruitment of CMS structures.
    Social neuroscience 02/2009; 4(3):197-211. DOI:10.1080/17470910802250519 · 2.87 Impact Factor

Similar Publications