Stronger effect of amyloid load than APOE genotype on cognitive decline in healthy older adults
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Abstract
Objective: Although the APOE ϵ4 allele is associated with more rapid decline in memory in healthy older adults, the significance of elevated cerebral β-amyloid (Aβ) load for longitudinal changes in cognition is unclear.
Methods: Healthy and cognitively normal older adults (n = 141; mean age 76 years) underwent PET neuroimaging for cerebral Aβ, APOE genotyping, and cognitive assessment as part of their baseline assessment in the Australian Imaging Biomarkers and Lifestyle study. Cognitive function was reassessed 18 months later.
Results: Linear mixed-model analyses adjusted for baseline cognitive function indicated that, relative to individuals with low cerebral Aβ, individuals with high cerebral Aβ showed significantly greater decline in working memory and verbal and visual episodic memory at 18 months. Compared with noncarriers, APOE ϵ4 carriers showed a greater decline in visual memory at the 18-month assessment. No interaction between APOE ϵ4 and cerebral Aβ load was observed for any measure of cognitive function.
Conclusions: In this prospective study of healthy older adults, high cerebral Aβ load was associated with greater decline in episodic and working memory over 18 months. The APOE ϵ4 genotype was also associated with a decline in visual memory, although the effect was less than that observed for cerebral Aβ load.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- AIBL=
- Australian Imaging Biomarkers and Lifestyle;
- ANCOVA=
- analysis of covariance;
- CVLT-II=
- California Verbal Learning Test, Second Edition;
- DET=
- Detection task;
- DET-IDN=
- Psychomotor-Attention Composite;
- IDN=
- Identification task;
- LMM=
- linear mixed model;
- MCI=
- mild cognitive impairment;
- OBK=
- One Back task;
- OCL=
- One Card Learning task;
- OCL-OBK=
- Working Memory-Learning Composite;
- PAL=
- Paired Associate Learning task;
- PiB=
- Pittsburgh compound B;
- SUV=
- standardized uptake value;
- SUVR=
- standardized uptake value ratio
Footnotes
-
AIBL Research Group Coinvestigators are listed on the Neurology® Web site at www.neurology.org.
Supplemental data at www.neurology.org
- Received February 22, 2012.
- Accepted May 29, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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