Publication Type | Academic Article |
Authors | Protas H, Chen K, Langbaum J, Fleisher A, Alexander G, Lee W, Bandy D, de Leon M, Mosconi L, Buckley S, Truran-Sacrey D, Schuff N, Weiner M, Caselli R, Reiman E |
Journal | JAMA Neurol |
Volume | 70 |
Issue | 3 |
Pagination | 320-5 |
Date Published | 03/01/2013 |
ISSN | 2168-6157 |
Keywords | Alzheimer Disease, Cognition, Glucose, Gyrus Cinguli, Hippocampus |
Abstract | OBJECTIVE: To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. DESIGN: Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. SETTING: Academic medical center. PARTICIPANTS: A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. MAIN OUTCOME MEASURES: The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. RESULTS: Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P < .05, determined by use of pairwise Fisher z tests). CONCLUSIONS: Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease. |
DOI | 10.1001/2013.jamaneurol.286 |
PubMed ID | 23599929 |
PubMed Central ID | PMC3745014 |