BackgroundResearch has revealed that manifest Alzheimer's disease (AD) dementia is preceded by preclinical and prodromal phases during which pathology is accumulating but function remains intact. This understanding and concern that disease-modifying interventions initiated at the dementia stage may come too late in the neurodegenerative process to be successful has led to a paradigm shift in AD clinical trials. AD trials now enroll patients with mild cognitive impairment (MCI) and persons with no cognitive symptoms. Trial designs are similar to those enrolling dementia participants. We set out to test the hypothesis that attitudes towards trial design features differ among different potential AD trial populations.
MethodsWe sent a survey composed of 37 items assessing specific trial elements to 246 cognitively normal, MCI, and AD dementia participants at the University of California Los Angeles (UCLA) Alzheimer's Disease Research Center (ADRC), from whom we received 91 responses (37 cognitively normal, 32 MCI, and 22 dementia). To quantify willingness to enroll, we created three composite scenarios by summing responses and fitting proportional odds models with a binary outcome variable for whether patients were highly willing to participate in low-, moderate-, or high-risk and burden trials.
ResultsMCI participants less frequently correctly self-identified their diagnoses than those with dementia or normal cognition. Compared to dementia patients, the odds of participating in a low-risk, low-burden trial were 12% lower for MCI patients (odds ratio (OR) = 0.88, 95% confidence interval (CI) 0.23-3.29) and 70% lower (OR = 0.30, 95% CI 0.08-1.09) for cognitively normal participants. With increasing risk and burden, willingness to enroll decreased and the gap in relative willingness between diagnostic groups increased. In the medium-risk, medium-burden scenario, the estimated OR was 0.64 (95% CI 0.17-2.40) for MCI and 0.21 for the cognitively normal (95% CI 0.06-0.77). In the high-risk, high-burden scenario, the estimated OR indicated reduced willingness for MCI (OR = 0.27, 95% CI 0.06-1.15) and cognitively normal respondents (OR = 0.12, 95% CI 0.03-0.54).
ConclusionsThese results suggest that AD trials enrolling predementia populations, especially those requiring frequent visits and implementing biomarker testing procedures, may encounter challenges to enrollment.