INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression: The INCREASE study

Alzheimer’s disease (AD) represents one of the most important public health issues our society is facing today. An estimated 5 million people age 65 and older in the United States (US) are currently living with AD, and this number may nearly triple by 2050. The National Alzheimer’s Project Act (NAPA) 2015 report emphasizes the need for identifying preventive strategies that can delay symptomatic disease onset to reduce this growing population burden. While much emphasis has been placed on developing and testing effective diseasemodifying strategies targeting this asymptomatic preclinical phase of AD (pAD), little emphasis has been placed on currently available strategies that target cognitive reserve, potentially delaying symptom onset, shortening the overall course of symptomatic disease, and substantially reducing the financial and societal impact of AD today. We hypothesize that targeted reductions in inappropriate medication use (Beers Criteria 2015), will bolster cognitive reserve in subjects at risk for AD, delaying the onset of clinical symptoms, and reducing the prevalence and duration of symptomatic disease. The impact of this strategy, if successful, includes a dramatic reduction in overall health care expenditures for the millions affected by AD by delaying the symptomatic phase of disease in accord with NAPA aims. Our specific aims are: Specific Aim 1. Conduct a 12 months, randomized, placebo-controlled trial to evaluate the impact of a patientcentered, pharmacist-physician team medication therapy management intervention in increasing cognitive reserve by reducing unnecessary and inappropriate prescribing in community-dwelling, elderly, non-demented subjects. Specific Aim 2 (exploratory). Evaluate the impact of preclinical amyloid burden on cognitive reserve deficits and decline (measured as cognitive reserve ratio) to evaluate efficacy of delaying symptomatic disease progression in pAD. While not eliminating AD or shortening duration of biological disease, the delay in symptom onset and progression to functional decline resulting from reduction in inappropriate medication use could lessen AD prevalence and significantly reduce healthcare expenditures related to not only AD, but potentially all forms of dementia involving a prodromal asymptomatic period. Study results would enable the larger implementation of similar medication management strategies in clinical practice to address the need for multifaceted preventive strategies to maintain cognitive health in the aging population.