Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for alzheimer disease

Hillary D. Protas, Kewei Chen, Jessica B.S. Langbaum, Adam S. Fleisher, Gene E. Alexander, Wendy Lee, Daniel Bandy, Mony J. De Leon, Lisa Mosconi, Shannon Buckley, Diana Truran-Sacrey, Norbert Schuff, Michael W. Weiner, Richard J. Caselli, Eric M. Reiman

Research output: Contribution to journalArticle

80 Scopus citations

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-middleaged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) e4 allele, reflecting 3 levels of risk for lateonset 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 e4 homozygotes, e4 heterozygotes, and noncarriers. Setting: Academic medical center. Participants: A total of 31 e4 homozygotes, 42 e4 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 e4 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.

Original languageEnglish (US)
Pages (from-to)320-325
Number of pages6
JournalJAMA Neurology
Volume70
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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    Protas, H. D., Chen, K., Langbaum, J. B. S., Fleisher, A. S., Alexander, G. E., Lee, W., Bandy, D., De Leon, M. J., Mosconi, L., Buckley, S., Truran-Sacrey, D., Schuff, N., Weiner, M. W., Caselli, R. J., & Reiman, E. M. (2013). Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for alzheimer disease. JAMA Neurology, 70(3), 320-325. https://doi.org/10.1001/2013.jamaneurol.286