Technology and Dementia Preconference

The detection of progression is key to the statistical power of placebo-controlled clinical trials. This is a challenge in dementia, as disease progression is confounded with natural aging, and as widely used assessments (CDR, ADAS-Cog) lack sensitivity and are administered only infrequently and in specialist settings. We report a non-interventional study conducted with 10 pharma companies to evaluate the feasibility and value of capturing repeated multimodal digital assessments with Alzheimer's dementia patients, using the NeuLogiq^TM platform in the home over 12 months. The difference in progression between mild dementia and matched controls serves as a model of placebo vs. an efficacious intervention. We quantify the statistical power of NeuLogiq digital measures, relative to conventional endpoints.

Seven UK sites recruited Alzheimer's type mild dementia patients (n = 59, ACE-III scores >60 and ≤88) and controls (n = 60). Participants were asked to perform 8 cognitive tasks presented on a tablet with synchronous low-burden EEG, autonomously at home. Overnight EEG was also recorded. NeuLogiq sessions were staggered throughout the year, with 26 samples requested per task. Benchmark paper-based assessments (including ADAS-Cog) were administered in-clinic (months 0, 6, 12) and blood plasma was collected (months 6, 12). Progression was analyzed with mixed effects models, for benchmarks and a predefined selection of Cumulus variables.

Over 52 weeks, there was a real but modest difference in progression on ADAS-Cog (beta=2.03, p = 0.021) and DSST (beta=-5.67, p = 0.006), and no significant difference on VPA, with all showing familiarization effects (Fig. 1). Of the 41 predefined NeuLogiq measures, several exhibited a similar/larger effect size to ADAS-Cog (Fig. 2). Two survived correction for multiple comparisons: tablet-based associative memory task (beta=-4.52, p <0.001) and psychomotor task (beta= 42.4, p <0.001). Post-hoc analysis showed that p -tau positive/negative patients were separated on the memory task, and on the symbol coding executive function task (Fig. 3).

Individual tablet-based tasks, completed autonomously at home by mild dementia patients, are more sensitive measurements of disease progression than ADAS-Cog. In on-going analysis we are quantifying the additional statistical power that multimodal/multivariate/composite measures may provide, and the resulting potential reductions in size, duration and risk of clinical trials in dementia.