Practice effects of daily functioning across the Alzheimer's disease spectrum

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Project Summary The main objective of this new application is to demonstrate that individuals with low practice effects on measures of daily functioning repeated across one week are more likely to cognitively progress over the following year. This project would also examine if practice effects on these performance-based functional scales differ across the disease spectrum in late adulthood by comparing older individuals who are cognitively intact to those with Mild Cognitive Impairment and Alzheimer's disease. In an exploratory aim, the relationship between practice effects on these functional scales and various biomarkers of Alzheimer's disease (e.g., hippocampal volumes via MRI, amyloid deposition via PET, APOE e4) will be studied. These findings would add to the supporting evidence of practice effects as a marker of diagnosis, prognosis, and treatment response in normal aging, Mild Cognitive Impairment, and dementing illnesses. However, it will extend our prior work by focusing on practice effects on functional measures (whereas our prior work looked at practice effects on cognitive tests). By realizing the aims of this pragmatic project, we would be able to offer more efficient screening of potential participants for clinical trials, which would reduce participant burden and financial costs associated with these trials. Practice effects could also be used to enrich trials with those more likely to progress and to monitor treatment benefit as a proximal outcome measure. Practice effects also have considerable clinical benefits for diagnosis and prognosis of cognitive disorders in late life. This project is consistent with the mission of the National Institute on Aging. Relevance. Current clinical trials in Mild Cognitive Impairment and Alzheimer's disease require participants to progress/decline across the trial to accurately evaluate the experimental intervention. Although existing biomarkers (e.g., tau and amyloid imaging) are being used to identify those most likely to progress, these biomarkers are expensive and invasive. Cheaper, less invasive, and more sensitive biomarkers are clearly needed to make these trials more efficient. We propose that practice effects on performance-based functional measures might fill this important gap in the literature. In the current pragmatic project, we expect to provide clinicians and researchers with a new tool (i.e., practice effects on functional scales) for predicting cognitive decline in seniors with and without cognitive impairments. We expect to provide supporting evidence to include practice effects in future clinical trials in normal aging, Mild Cognitive Impairment, and Alzheimer's disease.