Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease
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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.
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Cognitively intact children of AD mothers, relative to children of AD fathers, show greater age-associated brain atrophy, faster longitudinal brain atrophy, increased Aβ plaque deposition, elevated CSF oxidative stress markers, and AD-like CSF Aβ changes.
“Subsequent studies found that the cognitively intact children of AD mothers, relative to the cognitively intact children of AD fathers, show greater degrees of age-associated brain atrophy, faster rates of longitudinal brain atrophy, increased Aβ plaque deposition, elevated cerebrospinal fluid (CSF) oxidative stress markers, and AD-like CSF Aβ changes [130-137].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [135]
Maternal inheritance appears to determine several AD endophenotypes.
“Maternal inheritance appears to determine several AD endophenotypes.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [135]
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- Authors
- Honea, R. A., Swerdlow, R. H., Vidoni, E. D., & Burns, J. M.
- Affiliations
- University of Kansas (US)
- Venue
- Neurology
- Published
- 2011-03
- Volume
- 76
- Issue
- 9
- Pages
- 822-829
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3053329
- OpenAlex
- W2011089487
- Cited by
- 99
- References
- 41
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 13 · 2013: 12 · 2012: 13
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R21AG029615, R03AG026374)
- National Institute of Neurological Disorders and Stroke (K23NS058252)
- National Center for Research Resources (M01RR023940)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- Alzheimer's disease, family history (medicine), gray matter atrophy, maternal history, paternal history, precuneus, parahippocampal gyrus, hippocampus, APOE ε4, brain aging, cognitively normal elderly, voxel-based morphometry
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Cerebral Cortex, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Mothers, Risk Factors, Disease Progression, Genetic Predisposition to Disease, Parahippocampal Gyrus, Apolipoprotein E4
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