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

Document Type



Lippincott Williams and Wilkins


Centre of Excellence for Alzheimer's Disease Research and Care




Originally published as : Lim, Yen Ying (04.2016). "Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease.". Neurology (0028-3878), 86 (17), p. 1635-1642. Article found here


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. © 2016 American Academy of Neurology.