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

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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

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Gyrus Cinguli
Alzheimer Disease
Glucose
Apolipoprotein E4
Homozygote
Apolipoproteins E
Heterozygote
Metabolism
Alzheimer's Disease
Person
Genetic Risk
Neuropsychological Tests
Fluorodeoxyglucose F18
Brain
Positron-Emission Tomography
Alleles
Magnetic Resonance Imaging
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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

In: JAMA Neurology, Vol. 70, No. 3, 03.2013, p. 320-325.

Research output: Contribution to journalArticle

Protas, HD, Chen, K, Langbaum, JBS, Fleisher, AS, Alexander, GE, Lee, W, Bandy, D, De Leon, MJ, Mosconi, L, Buckley, S, Truran-Sacrey, D, Schuff, N, Weiner, MW, Caselli, RJ & Reiman, EM 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, vol. 70, no. 3, pp. 320-325. https://doi.org/10.1001/2013.jamaneurol.286
Protas, Hillary D. ; Chen, Kewei ; Langbaum, Jessica B S ; Fleisher, Adam S. ; Alexander, Gene E ; Lee, Wendy ; Bandy, Daniel ; De Leon, Mony J. ; Mosconi, Lisa ; Buckley, Shannon ; Truran-Sacrey, Diana ; Schuff, Norbert ; Weiner, Michael W. ; Caselli, Richard J. ; Reiman, Eric M. / 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. In: JAMA Neurology. 2013 ; Vol. 70, No. 3. pp. 320-325.
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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.",
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T1 - 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

AU - Protas, Hillary D.

AU - Chen, Kewei

AU - Langbaum, Jessica B S

AU - Fleisher, Adam S.

AU - Alexander, Gene E

AU - Lee, Wendy

AU - Bandy, Daniel

AU - De Leon, Mony J.

AU - Mosconi, Lisa

AU - Buckley, Shannon

AU - Truran-Sacrey, Diana

AU - Schuff, Norbert

AU - Weiner, Michael W.

AU - Caselli, Richard J.

AU - Reiman, Eric M.

PY - 2013/3

Y1 - 2013/3

N2 - 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.

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