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IC‐P2‐111: Regional hypometabolism in cognitively normal Hispanic carriers of the apolipoprotein E ϵ4 allele
Author(s) -
Langbaum Jessica,
Reiman Eric M.,
Chen Kewei,
Alexander Gene E.,
Bandy Daniel,
Smilovici Oded,
Lee Wendy,
Recshke Cole,
Caselli Richard J.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.2566
Subject(s) - posterior cingulate , apolipoprotein e , precuneus , dementia , psychology , allele , medicine , oncology , disease , neuroscience , cortex (anatomy) , genetics , cognition , biology , gene
Background: Although the apolipoprotein E (APOE) 4 allele is an established susceptibility gene for late-onset Alzheimer’s disease (AD), the extent to which it contributes to the risk of AD in Hispanic individuals remains to be clarified. We have previously demonstrated that non-Hispanic cognitively normal APOE 4 have abnormally low positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, and we proposed using PET CMRgl measurements as a quantitative, presymptomatic endophenotype for the assessment of putative genetic and non-genetic risk factors. Our objective was to test the hypothesis that cognitively normal, late-middle aged Hispanic-American APOE 4 carriers of European descent have abnormally low CMRgl in AD-affected brain regions. Methods: SPM5 was used to compare FDG PET images in 11 cognitively normal 4 carriers and 16 non-carriers, 54.6 6.4 years of age, from Arizona’s Hispanic community. Results: The subject groups did not differ significantly in their age or educational level, their gender or reported family history of dementia distribution, or their Mini-Mental State Examination (MMSE) scores (29.5 0.6), or neuropsychological scores. Consistent with our findings in non-Hispanic subjects, Hispanic 4 carriers had significantly lower CMRgl than non-carriers in previously identified AD-related hypometabolic regions including the posterior cingulate (P 0.05 after correction for multiple comparisons in this AD-affected search region), extending into midcingulate cortex, and the precuneus and parietal regions (p 0.005, uncorrected). They also had lower CMRgl in hippocampus, thalamus, caudate and anterior cingulate cortex (p 0.0005, uncorrected). Conclusions: Our brain imaging findings support the relevance of the APOE 4 allele to the risk of late-onset AD in Hispanic persons of European descent, and it supports the inclusion of Hispanic subjects in future studies using PET as a surrogate endpoint in 4 carriers to evaluate putative riskreducing and prevention therapies.