Magnetic Resonance Imaging Traits in Siblings Discordant for Alzheimer Disease
Open accessAbstract
BACKGROUND: Magnetic resonance imaging (MRI) can aid clinical assessment of brain changes potentially correlated with Alzheimer disease (AD). MRI traits may improve our ability to identify genes associated with AD‐outcomes. We evaluated semi‐quantitative MRI measures as endophenotypes for genetic studies by assessing their association with AD in families from the Multi‐Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) Study. METHODS: Discordant siblings from multiple ethnicities were ascertained through a single affected proband. Semi‐quantitative MRI measures were obtained for each individual. The association between continuous/ordinal MRI traits and AD were analyzed using generalized estimating equations. Medical history and Apolipoprotein E (APOE)ɛ4 status were evaluated as potential confounders. RESULTS: Comparisons of 214 affected and 234 unaffected subjects from 229 sibships revealed that general cerebral atrophy, white matter hyperintensities (WMH), and mediotemporal atrophy differed significantly between groups (each at P < .0001) and varied by ethnicity. Age at MRI and duration of AD confounded all associations between AD and MRI traits. Among unaffected sibs, the presence of at least one APOE ɛ 4 allele and MRI infarction was associated with more WMH after adjusting for age at MRI. CONCLUSION: The strong association between MRI traits and AD suggests that MRI traits may be informative endophenotypes for basic and clinical studies of AD. In particular, WMH may be a marker of vascular disease that contributes to AD pathogenesis.
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Cross-sectional studies of CVBI in convenience samples often find increased SBI and WMLs in subjects with dementia, consistent with community-based pathological studies.
“Cross-sectional studies of CVBI in convenience samples often find increased evidence of both SBI and WMLs in subjects with dementia,254,255 consistent with recent community-based pathological studies.12”
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- Authors
- Cuenco, K. T., Green, R. C., Zhang, J., Lunetta, K., Erlich, P. M., Cupples, L. A., Farrer, L. A., DeCarli, C., & for the MIRAGE Study Group
- Affiliations
- Boston University (US)
- Corresponding author
- Cuenco, Karen T.
- Cupples, L. Adrienne
- ORCID
- Venue
- Journal of Neuroimaging
- Publisher
- Wiley
- Published
- 2008-07
- Volume
- 18
- Issue
- 3
- Pages
- 268-275
- ISSN
- 1051-2284 (ISSN-L)
- 1552-6569
- PMC
- PMC2778266
- OpenAlex
- W1986146023
- Cited by
- 27
- References
- 58
- Citations by year
- 2023: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 4
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute on Aging (P30AG010129, R01-HG/AG-02213, K24AG027841, P30AG013846, R01AG009029, R01 AG09029, P30-AG13846))
- National Human Genome Research Institute (R01HG002213)
- 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, endophenotypes, brain atrophy, white matter hyperintensities, APOE ε4, vascular disease, ethnic differences
- MeSH terms
- Aged, Alzheimer Disease, Atrophy, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Phenotype, Regression Analysis, Risk Factors, Confounding Factors, Epidemiologic, Statistics, Nonparametric, Siblings, Apolipoprotein E4
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