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Abstract
Objective: Beyond age, having a family history is the most significant risk factor for Alzheimer disease (AD). This longitudinal brain imaging study examines whether there are differential patterns of regional gray matter atrophy in cognitively healthy elderly subjects with (FH+) and without (FH−) a family history of late-onset AD.
Methods: As part of the KU Brain Aging Project, cognitively intact individuals with a maternal history (FHm, n = 11), paternal history (FHp, n = 10), or no parental history of AD (FH−, n = 32) similar in age, gender, education, and Mini-Mental State Examination (MMSE) score received MRI at baseline and 2-year follow-up. A custom voxel-based morphometry processing stream was used to examine regional differences in atrophy between FH groups, controlling for age, gender, and APOE ϵ4 (APOE4) status. We also analyzed APOE4-related atrophy.
Results: Cognitively normal FH+ individuals had significantly increased whole-brain gray matter atrophy and CSF expansion compared to FH−. When FH+ groups were split, only FHm was associated with longitudinal measures of brain change. Moreover, our voxel-based analysis revealed that FHm subjects had significantly greater atrophy in the precuneus and parahippocampus/hippocampus regions compared to FH− and FHp subjects, independent of APOE4 status, gender, and age. Individuals with an ε4 allele had more regional atrophy in the frontal cortex compared to ε4 noncarriers.
Conclusions: We conclude that FHm individuals without dementia have progressive gray matter volume reductions in select AD-vulnerable brain regions, specifically the precuneus and parahippocampal gyrus. These data complement and extend reports of regional cerebral metabolic differences and increases in amyloid-β burden in FHm subjects, which may be related to a higher risk for developing AD.
Footnotes
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Study funding: Supported by grants R03AG026374 and R21 AG029615 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 space, expertise, and nursing support.
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Supplemental data at www.neurology.org
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- AD
- Alzheimer disease
- CDR
- Clinical Dementia Rating
- FH+
- with family history of late-onset Alzheimer disease
- FH−
- without family history of late-onset Alzheimer disease
- FHm
- maternal history of Alzheimer disease
- FHp
- paternal history of Alzheimer disease
- GLM
- general linear model
- GMChange
- gray matter volume change image
- MCI
- mild cognitive impairment
- MMSE
- Mini-Mental State Examination
- mtDNA
- mitochondrial DNA
- VBM
- voxel-based morphometry
- Received August 4, 2010.
- Accepted November 12, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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