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September 06, 2011; 77 (10) Articles

Magnetic resonance spectroscopy, β-amyloid load, and cognition in a population-based sample of cognitively normal older adults

K. Kantarci, V. Lowe, S.A. Przybelski, M.L. Senjem, S.D. Weigand, R.J. Ivnik, R. Roberts, Y.E. Geda, B.F. Boeve, D.S. Knopman, R.C. Petersen, C.R. Jack
First published August 24, 2011, DOI: https://doi.org/10.1212/WNL.0b013e31822dc7e1
K. Kantarci
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V. Lowe
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S.A. Przybelski
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M.L. Senjem
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S.D. Weigand
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Y.E. Geda
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B.F. Boeve
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R.C. Petersen
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Citation
Magnetic resonance spectroscopy, β-amyloid load, and cognition in a population-based sample of cognitively normal older adults
K. Kantarci, V. Lowe, S.A. Przybelski, M.L. Senjem, S.D. Weigand, R.J. Ivnik, R. Roberts, Y.E. Geda, B.F. Boeve, D.S. Knopman, R.C. Petersen, C.R. Jack
Neurology Sep 2011, 77 (10) 951-958; DOI: 10.1212/WNL.0b013e31822dc7e1

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Abstract

Objective: To determine the relationship between proton magnetic resonance spectroscopy (1H MRS) metabolites and β-amyloid (Aβ) load and the effects of Aβ load on the association between 1H MRS metabolites and cognitive function in cognitively normal older adults.

Methods: We studied 311 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging from January 2009 through September 2010. Participants underwent 11C-Pittsburgh compound B (PiB) PET, 1H MRS from the posterior cingulate gyri, and neuropsychometric testing to assess memory, attention/executive, language, and visual-spatial domain functions within 6 months. Partial Spearman rank order correlations were adjusted for age, sex, and education.

Results: Higher PiB retention was associated with abnormal elevations in myoinositol (mI)/creatine (Cr) (partial rs = 0.17; p = 0.003) and choline (Cho)/Cr (partial rs = 0.13; p = 0.022) ratios. Higher Cho/Cr was associated with worse performance on Auditory Verbal Learning Test Delayed Recall (partial rs = −0.12; p = 0.04), Trail Making Test Part B (partial rs = 0.12; p = 0.04), Wechsler Adult Intelligence Scale–Revised (WAIS-R) Digit Symbol (partial rs = −0.18; p < 0.01), and WAIS-R Block Design (partial rs = −0.12; p = 0.03). Associations between 1H MRS metabolites and cognitive function were not different among participants with high vs low PiB retention.

Conclusion: In cognitively normal older adults, the 1H MRS metabolite ratios mI/Cr and Cho/Cr are associated with the preclinical pathologic processes in the Alzheimer disease cascade. Higher Cho/Cr is associated with worse performance on domain-specific cognitive tests independent of Aβ load, suggesting that Cho/Cr elevation may also be dependent on other preclinical dementia pathologies characterized by Cho/Cr elevation such as Lewy body or ischemic vascular disease in addition to Aβ load.

Glossary

GLOSSARY
Aβ=
β-amyloid;
AD=
Alzheimer disease;
AVLT=
Auditory Verbal Learning Test;
Cho=
choline;
Cr=
creatine;
GM=
gray matter;
1H MRS=
proton magnetic resonance spectroscopy;
MCI=
mild cognitive impairment;
MCSA=
Mayo Clinic Study of Aging;
mI=
myoinositol;
MPRAGE=
magnetization-prepared rapid gradient echo;
NAA=
N-acetylaspartate;
PiB=
11C-Pittsburgh compound B;
SV=
single voxel;
WAIS-R=
Wechsler Adult Intelligence Scale–Revised

Footnotes

  • Study funding: Supported by the NIH (K23-AG030935, R01-AG11378, and U01-AG 06786). Support for several investigators was provided by the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation and NIH Construction Grant (C06-RR018898).

  • Editorial, page 932

  • Supplemental data at www.neurology.org

  • Received December 23, 2010.
  • Accepted April 1, 2011.
  • Copyright © 2011 by AAN Enterprises, Inc.
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