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. 2013 Mar 1;70(3):320-5.
doi: 10.1001/2013.jamaneurol.286.

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  1 , 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
Affiliations

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 et al. JAMA Neurol. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mosconi has a patent on a technology that was licensed to Abiant Inc by New York University and, as such, has a financial interest in this license agreement and holds stock and stock options in the company. Dr Mosconi has also received compensation for consulting services from Abiant Inc. Dr Weiner reported that he was on the scientific advisory boards of Lilly, Araclon, Institut Catala de Neurociencies Aplicades, Gulf War Veterans Advisory Committee, and Biogen Idec in 2010 and Pfizer in 2011; that he consulted for AstraZeneca, Araclon, Medivation/Pfizer, Ipsen, TauRx Therapeutics, Bayer HealthCare, Biogen Idec, ExonHit Therapeutics, Servier, and Synarc in 2010 and Pfizer and Janssen in 2011; that he received funding for travel from NeuroVigil, CHRU Hôpital Roger Salengro, Siemens, AstraZeneca, Geneva University Hospitals, Lilly, University of California, San Diego–Alzheimer’s Disease Neuroimaging Initiative (ADNI), Paris University, Institut Catala de Neurociencies Aplicades, University of New Mexico School of Medicine, Ipsen, and Clinical Trials on Alzhimer’s Disease in 2010 and Pfizer, The Alzheimer’s & Parkinson’s Conference, Paul Sabatier University, Novartis, and Tohoku University in 2011; that he was on the editorial advisory board of Alzheimer’s Disease & Dementia and Magnetic Resonance Imaging; that he received honoraria from NeuroVigil and Institut Catala de Neurociencies Aplicades in 2010 and Pharmaceuticals and Medical Devices Agency/Japanese Ministry of Health, Labour, and Welfare and Tohoku University in 2011; that he received commercial entities research support from Merck and Avid; that he received government entities research support from the US Department of Defense and the Department of Veterans Affairs; and that he has stock options in Synarc and Elan. The organizations contributing to the foundation for the National Institutes of Health, and thus to the National Institute on Aging–funded ADNI, are Abbott, the Alzheimer’s Association, the Alzheimer’s Drug Discovery Foundation, the Anonymous Foundation, AstraZeneca, Bayer HealthCare, BioClinica (ADNI 2), Bristol-Myers Squibb, the Cure Alzheimer’s Fund, Eisai, Elan, Gene Network Sciences, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Lilly, Medpace, Merck, Novartis, Pfizer, Roche, Schering Plough, Synarc, and Wyeth.

Figures

Figure
Figure
Cerebral metabolic rate for glucose (CMRgl) in the posterior cingulate and the hippocampus, determined using positron emission tomography, and hippocampal volume, determined using magnetic resonance imaging, in APOE ε4 homozygotes (HM), heterozygotes (HT), and noncarriers (NC). The CMRgl measurements are normalized to whole-brain measurement, whereas the hippocampal volumes are normalized for the variation in total intracranial volume. There is a significant decrease only with posterior cingulate CMRgl from noncarriers to homozygotes of the APOE ε4 allele (analysis of variance: P = .001; linear trend: P = .0003). Error bars indicate standard deviation.
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Comment in

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