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Abstract
Objective: To examine whether β-amyloid (Aβ) and APOE ε4 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN).
Methods: Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the contributions of APOE ε4 and Aβ on longitudinal change over a median of 1.49 years were examined. Cognitive decline was assessed with the Mini-Mental State Examination (MMSE) and Logical Memory (immediate and delayed recall scores).
Results: High Aβ participants were more likely to be APOE ε4+ than low Aβ participants. CNs who were both high Aβ and APOE ε4+ showed greater decline in Logical Memory immediate recall (p < 0.087), Logical Memory delayed recall (p < 0.024), and MMSE (p < 0.034) compared to all other groups (low Aβ/APOE ε4−, low Aβ/APOE ε4+, and high Aβ/APOE ε4−). No other pairwise contrast was significant for any cognitive measure.
Conclusions: Clinically normal individuals who are APOE ε4+ and have high Aβ showed the highest cognitive decline. These results suggest that Aβ and APOE ε4 are not redundant contributors of decline in aging but rather interact to promote decline during the short follow-up period examined in this study. Longer follow-up periods will be essential to fully elucidate the influence of Alzheimer disease risk factors on cognitive decline in aging.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- AIBL=
- Australian Imaging Biomarkers and Lifestyle Study of Ageing;
- CDR=
- Clinical Dementia Rating;
- CN=
- clinically normal older individuals;
- HABS=
- Harvard Aging Brain Study;
- MMSE=
- Mini-Mental State Examination;
- PiB=
- Pittsburgh compound B;
- ROI=
- region of interest
Footnotes
Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative database, the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing, and the Harvard Aging Brain Study. See the Acknowledgment section at the end of the article for more information.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
See page 1768
Editorial, page 1756
Supplemental data at Neurology.org
- Received October 18, 2013.
- Accepted in final form January 16, 2014.
- © 2014 American Academy of Neurology
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