A simple genetic stratification method for lower cost, more expedient clinical trials in early Alzheimer's disease: A preliminary study of tau PET and cognitive outcomes

IntroductionIdentifying individuals who are most likely to accumulate tau and exhibit cognitive decline is critical for Alzheimer's disease (AD) clinical trials. MethodsParticipants (N = 235) who were cognitively normal or with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative were stratified by a cutoff on the polygenic hazard score (PHS) at 65th percentile (above as high-risk group and below as low-risk group). We evaluated the associations between the PHS risk groups and tau positron emission tomography and cognitive decline, respectively. Power analyses estimated the sample size needed for clinical trials to detect differences in tau accumulation or cognitive change. ResultsThe high-risk group showed faster tau accumulation and cognitive decline. Clinical trials using the high-risk group would require a fraction of the sample size as trials without this inclusion criterion. DiscussionIncorporating a PHS inclusion criterion represents a low-cost and accessible way to identify potential participants for AD clinical trials.

Automated summary

This study found that individuals in the high-risk group, identified based on polygenic hazard score (PHS), exhibited faster tau accumulation and cognitive decline in Alzheimer's disease clinical trials. Trials using the high-risk group as inclusion criteria would require a smaller sample size. Incorporating PHS as an inclusion criterion is a cost-effective and accessible method to identify potential participants for AD clinical trials.