NEUROLOGY 2010;74:113-120
© 2010 American Academy of Neurology
Reduced gray matter volume in normal adults with a maternal family history of Alzheimer disease
R. A. Honea, DPhil,
R. H. Swerdlow, MD,
E. D. Vidoni, PT, PhD,
J. Goodwin, BS and
J. M. Burns, MD
From the University of Kansas School of Medicine, Kansas City, KS.
Address correspondence and reprint requests to Dr. Robyn A. Honea, University of Kansas School of Medicine, Department of Neurology, 2100 West 36th Ave., Suite 110, Kansas City, KS 66160 rhonea{at}kumc.edu or jburns2{at}kumc.edu
Objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Abbreviations: AD = Alzheimer disease; BA = Brodmann area; CDR = Clinical Dementia Rating; FH+ = parental family history of Alzheimer disease; FH– = no family history of Alzheimer disease; FHm = maternal family history of Alzheimer disease; FHp = paternal family history of Alzheimer disease; GMV = gray matter volume; mtDNA = mitochondrial DNA; TICV = total intracranial volume.
Supplemental data at www.neurology.org
Study funding: Supported by grants R03 AG026374, R21 AG029615, and R01 AG022407 from the National Institutes of Aging and K23NS058252 from the National Institute on Neurological Disorders and Stroke. The University of Kansas General Clinical Research Center (M01RR023940) provided essential space, expertise, and nursing support. The Hoglund Brain Imaging Center is supported by grant C76 HF00201.
Disclosure: Author disclosures are provided at the end of the article.
Received July 9, 2009. Accepted in final form October 21, 2009.
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PNAS,
March 30, 2010;
107(13):
5949 - 5954.
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