Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease
Yen Ying Lim1, Simon M Laws2, Victor L Villemagne2
1From The Florey Institute of Neuroscience and Mental Health (Y.Y.L., V.L.V., C.F., C.L.M., P.M.), The University of Melbourne, Parkville; Centre of Excellence for Alzheimer's Disease Research and Care (S.M.L., T.P., S.R.-S., R.N.M.), Edith Cowan University, Joondalup, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Academic Unit for Psychiatry of Old Age (D.A.), St. Vincent's Health, The University of Melbourne, Kew; National Ageing Research Institute (D.A.), Parkville, Australia; Department of Neurology (P.J.S.), Warren Alpert Medical School of Brown University, Providence, RI; Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship (O.S., P.B.), Australian e-Health Research Centre-BiaMedIA, Brisbane; Departments of Nuclear Medicine and Centre for PET (V.L.V., C.C.R.) and Medicine (V.L.V., C.C.R.), Austin Health, Heidelberg; Sir James McCusker Alzheimer's Disease Research Unit (S.M.L., T.P.), Hollywood Private Hospital, Perth; Co-operative Research Centre for Mental Health (S.M.L., T.P.), Carlton South; and CogState Ltd. (P.M.), Melbourne, Australia. yen.lim@florey.edu.au.
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.
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