Magnetic resonance imaging traits in siblings discordant for Alzheimer disease

Karen T. Cuenco, Robert C. Green, J. Zhang, Kathryn Lunetta, Porat M. Erlich, L. Adrienne Cupples, Lindsay A. Farrer, Charles DeCarli

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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)ε4 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 APOEε4 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.

Original languageEnglish (US)
Pages (from-to)268-275
Number of pages8
JournalJournal of Neuroimaging
Issue number3
StatePublished - Jul 2008


  • Alzheimer disease
  • Endophenotype
  • Genetic
  • MRI
  • White matter hyperintensities

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology
  • Neuroscience(all)
  • Radiological and Ultrasound Technology


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