P1‐259: Regional hypometabolism in cognitively normal Hispanic carriers of the apolipoprotein E–ϵ4 allele
Year: 2008
Type: article
Study design: Observational Study
Abstract: Although the apolipoprotein E (APOE) ϵ4 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 ϵ4 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 ϵ4 carriers of European descent have abnormally low CMRgl in AD-affected brain regions. SPM5 was used to compare FDG PET images in 11 cognitively normal ϵ4 carriers and 16 non-carriers, 54.6±6.4 years of age, from Arizona's Hispanic community. 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 ϵ4 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 mid-cingulate 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). Our brain imaging findings support the relevance of the APOE ϵ4 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 ϵ4 carriers to evaluate putative risk-reducing and prevention therapies.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4246020133