Does targeted medication therapy management increase cognitive reserve? Results from the INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer’s Symptomatic Expression (INCREASE) study

Background The INCREASE study is based on the hypothesis that targeted reductions in inappropriate medication use will bolster cognitive reserve (CR) in individuals at risk for Alzheimer’s Disease (AD), delaying the onset of clinical symptoms, and reducing the prevalence and duration of symptomatic disease. Method We conducted a 12‐month, randomized controlled trial to: (1) evaluate the impact of a medication therapy management (MTM) intervention in reducing unnecessary and inappropriate medication use in community‐dwelling, non‐demented older adults, (2) determine the impact of preclinical amyloid burden on CR deficits and decline to evaluate efficacy of delaying symptomatic disease progression in preclinical AD (pAD). Primary outcome measures included pre‐ to post‐intervention measures of: (1) medication use ( Medication Appropriateness Index, MAI); 2) CR Change Score (CRCS) defined as the difference in the scopolamine‐challenged vs unchallenged neurocognitive scores (Trail Making Tests A and B; California Verbal Learning Test, CVLT) . For the second aim, we used baseline determination of total brain relative standardized uptake values for amyloid β‐ positron emission tomography to examine the relative impact of pAD pathology on CRCS at baseline and over time in the placebo group, as well as the interplay of pAD pathology with inappropriate medication use at baseline and optimization of medication use after one year. Result We randomized 90 community‐dwelling participants (N=104 screened for eligibility). Mean (SD) age at enrollment was 73.9 (6.0), with N=57 (63%) female, and N=10 (10%) non‐white participants. At baseline, participants reported using a mean (SD) of 12.72 (4.87) medications, with 2.37 (1.29) potentially inappropriate (Beers 2015 criteria). In preliminary analyses, participants with pAD (N=29) had lower baseline CR for tests of executive function (mean (SD) change score ‐0.17 (1.37) and ‐0.13 (1.10) [p=0.90] for pAD and non‐pAD respectively) and total learning (‐0.85 (0.84) and ‐0.29 (0.83) [p=0.01]). At the time of submission, we anticipate that data collection will be finalized by March 31, 2021 and we are planning to present main study results during AAIC 2021. Conclusion The results of the INCREASE study will provide insights on the impact of optimizing medication use to bolster CR, as well as the interaction with preclinical amyloid burden.