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Abstract
Objective: To determine the relationship between β-amyloid (Aβ) load as measured by [11C]–Pittsburgh compound B (PiB) PET and cognitive function in cognitively normal older adults.
Methods: We studied 408 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging (MCSA) from January 2009 through March 2011. The participants underwent PiB PET and neuropsychometric testing within 6 months. The association between PiB retention and cognitive function was measured by partial correlation and an interaction with APOE status was tested using linear regression after adjusting for age, sex, and education.
Results: Higher PiB retention was associated with cognitive performance (Spearman partial r = −0.18; p < 0.01), specifically the memory, language, attention/executive, and visual-spatial processing domains in the whole group of participants. The association between PiB retention and cognition was modified by the APOE status on linear regression analysis even after controlling for the differences in the distribution of PiB values among APOE ϵ4 carriers and noncarriers (p = 0.02). Cognitive performance was associated with the Aβ deposition in the frontal, temporal, and parietal lobe association cortices in APOE ϵ4 carriers on SPM analysis (p < 0.001).
Conclusion: There is a modest association between PiB retention and cognitive function in cognitively normal older adults and this relationship between Aβ load and cognitive function is modified by APOE status. Whereas Aβ load is associated with greater cognitive impairment in APOE ϵ4 carriers, the cognitive function in APOE ϵ4 noncarriers is influenced less by the Aβ load, suggesting that APOE isoforms modulate the harmful effects of Aβ on cognitive function. Neurology® 2012;78:232–240
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- ANOVA=
- analysis of variance;
- GM=
- gray matter;
- MCSA=
- Mayo Clinic Study of Aging;
- MPRAGE=
- magnetization-prepared rapid gradient echo;
- PiB=
- Pittsburgh compound B;
- WAIS-R=
- Wechsler Adult Intelligence Scale—Revised
Footnotes
Study funding: NIH (K23 AG030935, R01 AG11378, 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 the NIH Construction Grant (NIH C06 RR018898).
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Editorial, page 228
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Supplemental data at www.neurology.org.
- Received March 9, 2011.
- Accepted July 7, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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