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Amyloid and APOE [epsilon]4 interact to influence short-term decline in preclinical Alzheimer disease.
Mormino, Elizabeth C. PhD; Betensky, Rebecca A. PhD; Hedden, Trey PhD; Schultz, Aaron P. PhD; Ward, Andrew BA; Huijbers, Willem PhD; Rentz, Dorene M. PsyD; Johnson, Keith A. MD; Sperling, Reisa A. MD; For the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing, and the Harvard Aging Brain Study
[Article] Neurology. 82(20):1760-1767, May 20, 2014.

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Objective: To examine whether [beta]-amyloid (A[beta]) and APOE [epsilon]4 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 [epsilon]4 and A[beta] 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 A[beta] participants were more likely to be APOE [epsilon]4 than low A[beta] participants. CNs who were both high A[beta] and APOE [epsilon]4 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 A[beta]/APOE [epsilon]4-, low A[beta]/APOE [epsilon]4 , and high A[beta]/APOE [epsilon]4-). No other pairwise contrast was significant for any cognitive measure.

Conclusions: Clinically normal individuals who are APOE [epsilon]4 and have high A[beta] showed the highest cognitive decline. These results suggest that A[beta] and APOE [epsilon]4 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.