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M.A. Dubbelman, J. Sanchez, A.P. Schultz, D.M. Rentz, R.E. Amariglio, S.A.M. Sikkes, R.A. Sperling, K.A. Johnson, G.A. Marshall, on behalf of the A4 Study team, full listing of team and site personnel available at

J Prev Alz Dis 2022;4(9):801-808

Background: Performance of cognitively complex “instrumental activities of daily living” (IADL) has previously been related to amyloid deposition in preclinical Alzheimer’s disease. Objectives: We aimed to investigate the relationship between IADL performance and cerebral tau accumulation in cognitively normal older adults. Design: Cross-sectional. Setting: Data was collected in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies. Participants: Participants (n = 447, age 71.9±4.9 years, 57.5% female) who underwent tau positron emission tomography were selected from the A4 and LEARN studies. Measurements: IADL performance was measured using the self- and study partner-reported versions of the Alzheimer’s Disease Cooperative Study Activities of Daily Living – Prevention Instrument (ADCS ADL-PI). We also investigated discordance between participants and their study partners. Cross-sectional associations between entorhinal and inferior temporal tau (independent variables) and ADCS ADL-PI total scores, item-level scores and discordance (dependent variables) were investigated in linear and logistic regressions. Analyses were adjusted for age, sex and education and a tau by amyloid interaction was also included. Results: Participants and their study partners reported high levels of IADL performance. Entorhinal and inferior temporal tau were related to study partner but not to self-reported total ADCS ADL-PI scores. The association was not retained after adjustment for global cerebral amyloid burden. At the item level, greater entorhinal tau was associated with study partner-reported difficulties remembering important dates (odds ratio (OR) = 1.24, 95% confidence interval (95%CI) = [1.06, 1.45], p = 0.008) and difficulties remembering the details of TV programs and movies (OR = 1.32, 95%CI = [1.08, 1.61], p = 0.007). Greater inferior temporal tau was associated with self-reported difficulties managing to find personal belongings (OR = 1.23, 95%CI = [1.04, 1.46], p = 0.018) and study partner-reported difficulties remembering the details of TV programs and movies (OR = 1.39, 95%CI = [1.11, 1.75], p = 0.005). Discordance between participant and study partner-report was more likely with greater entorhinal (OR = 1.18, 95%CI = [1.05, 1.33], p = 0.005) and inferior temporal tau burden (OR = 1.29, 95%CI = [1.10, 1.51], p = 0.002). Discussion: We found a cross-sectional relationship between study partner-reported everyday functioning and tau in cognitively normal older adults. Participants were more likely to self-report difficulties differently from their study partners when tau burden was higher. This may hint at an altered early-disease awareness of functional changes and underscores the importance of self-report of IADL functioning in addition to collateral report by a study partner.

M.A. Dubbelman ; J. Sanchez ; A.P. Schultz ; D.M. Rentz ; R.E. Amariglio ; S.A.M. Sikkes ; R.A. Sperling ; K.A. Johnson ; G.A. Marshall ; on behalf of the A4 Study team, full listing of team and site personnel available at ; (2022): Everyday Functioning and Entorhinal and Inferior Temporal Tau Burden in Cognitively Normal Older Adults. The Journal of Prevention of Alzheimer’s Disease (JPAD).

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