Reduced gray matter volume in normal adults with a maternal family history of Alzheimer disease

University of Kansas School of Medicine, Department of Neurology, 2100 West 36th Ave., Suite 110, Kansas City, KS 66160, USA.
Neurology (Impact Factor: 8.3). 01/2010; 74(2):113-20. DOI: 10.1212/WNL.0b013e3181c918cb
Source: PubMed

ABSTRACT A consistently identified risk factor for Alzheimer disease (AD) is family history of dementia, with maternal transmission significantly more frequent than paternal transmission. A history of maternal AD may be related to AD-like glucose consumption in cognitively healthy subjects. In this cross-sectional study, we tested whether cognitively healthy people with a family history of AD have less gray matter volume (GMV), an endophenotype for late-onset AD, than individuals with no family history, and whether decreases in GMV are different in subjects with a maternal family history.
As part of the Kansas University Brain Aging Project, 67 cognitively intact individuals with a maternal history of late-onset AD (FHm, n = 16), a paternal history of AD (FHp, n = 8), or no parental history of AD (FH-, n = 43), similar in age, gender, education, and Mini-Mental State Examination score, were scanned at 3 T. We used voxel-based morphometry to examine GMV differences between groups, controlling for age, gender, and apoE4.
Cognitively healthy individuals with a family history of late-onset AD had significantly decreased GMV in the precuneus, middle frontal, inferior frontal, and superior frontal gyri compared with FH- individuals. FHm subjects had significantly smaller inferior frontal, middle frontal, precuneus, and lingual gyri compared with FH- and FHp subjects.
Overall, maternal family history of Alzheimer disease (AD) in cognitively normal individuals is associated with lower gray matter volume in AD-vulnerable brain regions. These data complement and extend reports of cerebral metabolic differences in subjects with a maternal family history.


Available from: Jeffrey M Burns, Apr 09, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The ε4 allele of the apolipoprotein E (APOE4) is associated with an increased risk of developing Alzheimer's disease (AD). Hence, several studies have compared the brain characteristics of APOE4 carriers versus non-carriers in presymptomatic stages to determine early AD biomarkers. The present review provides an overview on APOE4-related brain changes in cognitively normal individuals, focusing on the main neuroimaging biomarkers for AD, i.e. cortical beta-amyloid (Aβ) deposition, hypometabolism and atrophy. The most consistent findings are observed with Aβ deposition as most studies report significantly higher cortical Aβ load in APOE4 carriers compared with non-carriers. Fluorodeoxyglucose-positron emission tomography studies are rare and tend to show hypometabolism in brain regions typically impaired in AD. Structural magnetic resonance imaging findings are the most numerous and also the most discrepant, showing atrophy in AD-sensitive regions in some studies but contradicting results as well. Altogether, this suggests a graded effect of APOE4, with a predominant effect on Aβ over brain structure and metabolism. Multimodal studies confirm this view and also suggest that APOE4 effects on brain structure and function are mediated by both Aβ-dependent and Aβ-independent pathological processes. Neuroimaging studies on asymptomatic APOE4 carriers offer relevant information to the understanding of early pathological mechanisms of the disease, although caution is needed as to whether APOE4 effects reflect AD pathological processes, and are representative of these effects in non-carriers.
    Neuropsychology Review 08/2014; 24(3). DOI:10.1007/s11065-014-9263-8 · 5.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diffusion tensor imaging has been used extensively as a research tool to understand the structural changes associated with white matter pathology. Using water diffusion as the basis to construct anatomic details, diffusion tensor imaging offers the potential to identify structural and functional adaptations before gross anatomical changes, such as lesions and tumors, become apparent on conventional MRI. Over the past 10 years, further parameters, such as axial and radial diffusivity, have been developed to characterize white matter changes specific to axons and myelin. In this paper, the potential application and outstanding issues on the use of diffusion tensor imaging directional diffusivity as a biomarker in axonal and myelin damage in neurological disorders will be reviewed.
    Imaging in medicine 10/2013; 5(5):427-440. DOI:10.2217/iim.13.49
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Various studies have suggested that the mitochondrial genome plays a role in late-onset Alzheimer's disease, although results are mixed. We used an endophenotype-based approach to further characterize mitochondrial genetic variation and its relationship to risk markers for Alzheimer's disease. We analyzed longitudinal data from non-demented, mild cognitive impairment, and late-onset Alzheimer's disease participants in the Alzheimer's Disease Neuroimaging Initiative with genetic, brain imaging, and behavioral data. We assessed the relationship of structural MRI and cognitive biomarkers with mitochondrial genome variation using TreeScanning, a haplotype-based approach that concentrates statistical power by analyzing evolutionarily meaningful groups (or clades) of haplotypes together for association with a phenotype. Four clades were associated with three different endophenotypes: whole brain volume, percent change in temporal pole thickness, and left hippocampal atrophy over two years. This is the first study of its kind to identify mitochondrial variation associated with brain imaging endophenotypes of Alzheimer's disease. Our results provide additional evidence that the mitochondrial genome plays a role in risk for Alzheimer's disease.
    PLoS ONE 09/2013; 8(9):e74158. DOI:10.1371/journal.pone.0074158 · 3.53 Impact Factor