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Aβ-related memory decline in APOE ε4 noncarriers

Lim, Y.Y., Laws, S.M., Villemagne, V.L., Pietrzak, R.H., Porter, T., Ames, D., Fowler, C., Rainey-Smith, S., Snyder, P.J., Martins, R.N., Salvado, O., Bourgeat, P., Rowe, C.C., Masters, C.L. and Maruff, P. (2016) Aβ-related memory decline in APOE ε4 noncarriers. Neurology, 86 (17). pp. 1635-1642.

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Objective: As the absence of Aβ-related memory decline in APOE ε4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ε4 carriers and noncarriers who were cognitively normal (CN).

Methods: CN older adults (n = 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments.

Results: Relative to Aβ− CN ε4 noncarriers, both Aβ+ CN ε4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ε4 carriers than in Aβ+ CN ε4 noncarriers. No cognitive decline was evident in Aβ− CN ε4 carriers.

Conclusions: In CN older adults, Aβ+ is associated with memory decline in ε4 noncarriers; however, the rate of this decline is much slower than that observed in ε4 carriers. These data indicate that the processes by which ε4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease.

Item Type: Journal Article
Publisher: Lippincott Williams & Wilkins
Copyright: © 2016 American Academy of Neurology
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