Abstract: We will conduct an open-label double-blind group assignment clinical trial testing serum “adipokine” proteins as the mediators of the Federal Drug Administration (FDA)-approved medication donepezil (Aricept®)’s effect on the latent dementia severity metric “δ”. Adipokines are inflammatory proteins released by adipose tissues and recently associated with cognitive decline. Our intent is to demonstrate multiple potential improvements in the conduct of any future dementia-related clinical trial. For example, the use of telephone assessment minimizes recruitment and assessment costs and protects participants from potential SARS-cov-2 exposure. The entire protocol could be administered by telephone, if necessary, in subjects unvaccinated against SARS-cov-2. In prior work, we have established the latent variable “δ” (for dementia) as a dementia-specific cognitive phenotype. We will use δ to equate study groups on their baseline dementia severity and set the recruitment threshold to maximize the potential for reversions back across δ’s dementia conversion threshold if treatment is effective. We will deploy a novel “Line of identity (LOI)” algorithm to further select cases most likely to benefit from our intervention (an example of precision medicine). We will use a second latent dementia severity metric (dTEL) as a comprehensive dementia-specific outcome. Finally, we will test a latent adipokine biomarker construct as a mediator of donepezil’s effect on δ. That will potentially establish a novel mechanism for acetylcholinesterase inhibition.