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O3‐10‐04: Performance on the memory binding test predicts incident aMCI and dementia: Results from the einstein aging study
Author(s) -
Mowrey Wenzhu,
Lipton Richard B.,
Buschke Herman
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.07.294
Subject(s) - dementia , medicine , geriatric depression scale , cognition , memory impairment , psychology , audiology , psychiatry , depressive symptoms , disease
in preclinical AD. However, currently we do not know how a clinically meaningful outcome would manifest over the 36 months of such clinical trials. One possibility is to consider the effect of apolipoprotein E (APOE) ε4 on Ab+ cognitive decline. We and others have reported that ε4 carriage reliably increases Ab related cognitive decline in preclinical AD over 36-months. Therefore ameliorating the effects of e4 on AB+ related change on the ADCSPACC could provide one benchmark for a clinically meaningful treatment effect in these trials. Methods:CN older adults (n1⁄4333) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Ab neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, and 36-month follow-ups. The ADCS-PACC was computed using scores from the California Verbal List Learning Test (2 edition), Logical Memory task, Mini Mental Status Examination and WAIS Digit Symbol Substitution Test. Ab PET neuroimaging was used to classify participants as Ab+ and APOE genotyping was used to classify participants as ε4 carriers or non-carriers. Results: No change in the ADCSPACC was observed over the 36 months in Ab+ ε4 non-carriers [mean (SD) slope1⁄40.00(0.243)]. In comparison, Ab+ ε4 carriers showed a significantly greater deterioration on the ADCS-PACC over 36-months [mean (SD) slope1⁄4 -0.243 (0.365)]. The difference in slopes over 36-months was, by convention, moderately large [d (95%CI)1⁄40.77 (0.45,1.09)]. There was no effect of ε4 carriage on subject memory or mood in Ab+ CN older adults. Conclusions: These data show that in Ab+ CN older adults, the ADCS-PACC is sensitive to moderation by ε4, with this effect moderate-to-large in magnitude. As APOE ε4 exerts a disease specific and clinically meaningful effect on risk for AD, it may be considered as a benchmark for determining a clinically meaningful effect in secondary prevention trials of preclinical AD.