Neuropsychological, Psychiatric, and Functional Correlates of Clinical Trial Enrollment.

Screen failure rates in Alzheimer's disease (AD) clinical trial research are unsustainable, with participant recruitment being a top barrier to AD research progress. The purpose of this project was to understand the neuropsychological, psychiatric, and functional features of individuals who failed screening measures for AD trials. Previously collected clinical data from 38 patients (aged 50-83) screened for a specific industry-sponsored clinical trial of MCI/early AD (Biogen 221AD302, [EMERGE]) were analyzed to identify predictors of AD trial screen pass/fail status. Worse performance on non-memory cognitive domains like crystalized knowledge, executive functioning, and attention, and higher self-reported anxiety, was associated with failing the screening visit for the EMERGE AD clinical trial, whereas we were not able to detect a relationship between screening status and memory performance, self-reported depression, or self-reported daily functioning. By identifying predictors of AD trial screen passing/failure, this research may influence decision-making about which patients are most likely to successfully enroll in a trial, thereby potentially lowering participant burden, maximizing study resources, and reducing costs.

Short-Term Practice Effects and Amyloid Deposition: Providing Information Above and Beyond Baseline Cognition.

BACKGROUND: Practice effects, which are improvements in cognitive test scores due to repeated exposure to testing materials, may provide information about Alzheimer's disease pathology, which could be useful for clinical trials enrichment. OBJECTIVES: The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to amyloid deposition on neuroimaging. PARTICIPANTS: Twenty-seven, non-demented older adults (9 cognitively intact, 18 with mild cognitive impairment) received amyloid imaging with 18F-Flutemetamol, and two cognitive testing sessions across one week to determine practice effects. RESULTS: A composite measure of 18F-Flutemetamol uptake correlated significantly with all seven cognitive tests scores on the baseline battery (r's = -0.61 - 0.59, all p's<0.05), with higher uptake indicating poorer cognition. Practice effects significantly added to the relationship (above and beyond the baseline associations) with 18F-Flutemetamol uptake on 4 of the 7 cognitive test scores (partial r's = -0.45 - 0.44, p's<0.05), with higher uptake indicating poorer practice effects. The odds ratio of being "amyloid positive" was 13.5 times higher in individuals with low practice effects compared to high practice effects. CONCLUSIONS: Short-term practice effects over one week may be predictive of progressive dementia and serve as an affordable screening tool to enrich samples for preventative clinical trials in Alzheimer's disease.