The main objective of this new application is to demonstrate that individuals with low practice effects on repeated cognitive testing across one week are likely to be identified as “positive” on amyloid imaging and other biomarkers associated with Alzheimer's disease. This project would also examine if short-term practice effects and amyloid deposition 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. 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. 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. Many current clinical trials in Mild Cognitive Impairment and Alzheimer's disease are using biomarkers (e.g., “positive” on amyloid imaging, atrophic hippocampi, APOE e4) as part of the inclusion criteria. Similarly, biomarkers are becoming increasingly important in the diagnosis of Alzheimer's disease and other types of dementia. However, many of these biomarkers are costly, invasive, provide little clinical information, and may be only completed at sites with unique resources. There is a need for more practical markers of disease and its progression, which could be used to enrich clinical trials. Practice effects, collected on cognitive testing across one week, may fill this important gap. In the current pragmatic project, we expect to provide clinicians and researchers with a new tool (i.e., practice effects) for predicting current amyloid positivity in seniors with and without cognitive impairments. We will also examine the relationship between short-term practice effects and other biomarkers associated with Alzheimer's disease (e.g., atrophic hippocampi, APOE e4, functional connectivity of brain networks). We expect to provide supporting evidence to include practice effects in future clinical trials in normal aging, Mild Cognitive Impairment, and Alzheimer's disease.

This project expects to inform clinical trials by providing a new tool (i.e., short-term practice effects) for predicting current amyloid positivity in seniors with and without cognitive impairment. This project will also examine the relationship between short-term practice effects and other biomarkers associated with Alzheimer's disease (e.g., atrophic hippocampi, APOE e4, functional connectivity of brain networks). By completing 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 enrich trials with those more likely to progress. Practice effects also have considerable clinical benefits for diagnosis and prognosis of cognitive disorders in late life.