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

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $254,575

## Abstract

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. To address this impeding population burden, the National Alzheimer's Project
Act (NAPA) 2015 report emphasized the need for identifying preventive strategies that can delay symptomatic
disease onset. While much emphasis has been placed on developing and testing effective disease-modifying
strategies targeting this asymptomatic preclinical phase of AD (pAD), little emphasis has been placed on
currently available strategies that target cognitive reserve, resulting in (1) delaying symptom onset, (2) shortening
the overall course of symptomatic disease, and (3) substantially reducing the financial and societal impact of AD.
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-month, randomized, placebo-controlled trial to evaluate the impact of our patient-
centered, pharmacist-physician team MTM intervention in reducing unnecessary and inappropriate medication
use in community-dwelling, elderly, non-demented subjects. Primary outcome measures will include pre- to post-
intervention measures of: (1) use of inappropriate medications as measured by the Medication Appropriateness
Index (MAI); 2) Cognitive Reserve Change Score (CRCS) defined as the difference in the scopolamine-
challenged vs unchallenged measures on the neurocognitive score.
Specific Aim 2 Evaluate the impact of preclinical amyloid burden on cognitive reserve deficits and decline
(measured as CRCS) 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.

## Key facts

- **NIH application ID:** 9890996
- **Project number:** 5R01AG054130-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** GREGORY A JICHA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,575
- **Award type:** 5
- **Project period:** 2016-07-15 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890996

## Citation

> US National Institutes of Health, RePORTER application 9890996, INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer’s Symptomatic Expression: The INCREASE study (5R01AG054130-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9890996. Licensed CC0.

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