Aβ-related memory decline in APOE ϵ4 noncarriers: Implications for Alzheimer disease

Yen Ying Lim, Simon M. Laws, Victor L. Villemagne, Robert H. Pietrzak, Tenielle Porter, David Ames, Christopher Fowler, Stephanie Rainey-Smith, Peter J. Snyder, Ralph N. Martins, Olivier Salvado, Pierrick Bourgeat, Christopher C. Rowe, Colin L. Masters, Paul Maruff

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1635-1642
Number of pages8
Issue number17
Publication statusPublished - 26 Apr 2016
Externally publishedYes

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