Regional cerebral tau predicts decline in everyday functioning across the Alzheimer’s disease spectrum

Abstract Background Emerging difficulty performing cognitively complex everyday tasks, or ‘instrumental activities of daily living’ (IADL) may be an early clinical sign of Alzheimer’s disease (AD). We aimed to investigate how changes over time in everyday functioning relate to cerebral tau burden across the AD clinical spectrum. Methods We included 581 participants (73.9 ± 7.6 years old; 52% female) from the Alzheimer’s Disease Neuroimaging Initiative who underwent tau positron emission tomography (PET) and completed at least two assessments of the Functional Activities Questionnaire (FAQ). Participants were classified as cognitively normal (n = 334) or symptomatic (n = 247). We analyzed the association between longitudinal FAQ scores and baseline tau in six temporal, parietal, and frontal brain regions in mixed-effects models. Models were run in the entire sample, as well as stratified by diagnostic group (cognitively normal or symptomatic). We additionally investigated tau-PET adjusted for, as well as interacting with, amyloid-β. Results Greater tau burden in several frontal, temporal, and parietal regions was associated with steeper decline over time in everyday functioning. These findings remained when adjusting for baseline global cortical amyloid-β; amyloid-β itself was only associated with change over time in FAQ scores when tau was not included in the model. When stratifying by diagnostic group, most associations between tau and everyday functioning, adjusted for amyloid-β, were present only in the symptomatic group. Conclusions The rate of change in everyday functioning is related to baseline tau burden in various brain regions, more strongly so than global cortical amyloid-β, specifically in cognitively symptomatic individuals. Longitudinal studies in incident dementia populations are needed to better understand functional changes in response to AD pathology across the disease

Using a digital tool to detect early changes in everyday functioning in older adults: A pilot study of the Assessment of Smartphone Everyday Tasks (ASSET)

Abstract INTRODUCTION To investigate the utility of a new digital tool for measuring everyday functioning in preclinical Alzheimer's disease, we piloted the Assessment of Smartphone Everyday Tasks (ASSET) application. METHODS Forty‐six participants (50.3 ± 27.1 years; 67% female; 20 young unimpaired, 17 old unimpaired, 9 mildly cognitively impaired) completed ASSET 7 times. ASSET comprises two main tasks, simulating a Patient Portal and a Calendar. We assessed ASSET's internal consistency, test–retest reliability, and user experience. RESULTS ASSET main tasks correlated with each other (r = 0.75, 95% confidence interval [CI] = [0.58, 0.86]). Performance on ASSET's Patient Portal related to cognition (r = 0.64, 95% CI = [0.42, 0.79]) and observer ratings of everyday functioning (r = 0.57, 95% CI = [0.24, 0.79]). Test–retest reliability was good (intraclass correlation coefficient = 0.87, 95% CI = [0.77, 0.93]). Most participants rated their experience with ASSET neutrally or positively. DISCUSSION ASSET is a promising smartphone‐based digital assessment of everyday functioning. Future studies may investigate its utility for early diagnosis and evaluation of treatment of Alzheimer's disease