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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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