Magnetic resonance imaging traits in siblings discordant for Alzheimer disease.
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)epsilon4 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 APOEepsilon4 allele and MRI infarction was associated with more WMH after adjusting for age at MRI.


CONCLUSIONS
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.
Cuenco
Karen T
KT
Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, MA 02118, USA. ktcuenco@bu.edu
Green
Robert C
RC
Zhang
J
J
Lunetta
Kathryn
K
Erlich
Porat M
PM
Cupples
L Adrienne
LA
Farrer
Lindsay A
LA
DeCarli
Charles
C
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D001284:Atrophy; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D012044:Regression Analysis; D012307:Risk Factors; D035781:Siblings; D018709:Statistics, Nonparametric
D053327:Apolipoprotein E4