Document Type

Journal Article

Publisher

Lippincott Williams and Wilkins

School

Centre of Excellence for Alzheimer's Disease Research and Care

RAS ID

21783

Comments

This is an Author's Accepted Manuscript of:

Lim, Yen Ying, Laws, S.M., Villemagne, V.L., Pietrzak, R.H., Porter, T., Ames, D., ... Maruff, P. (2016). "Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease.". Neurology, 86 (17), p. 1635-1642.

https://doi.org/10.1212/WNL.0000000000002604

Abstract

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.

DOI

10.1212/WNL.0000000000002604

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