Abstract Details

Title Repurposed Drugs for Alzheimer’s Disease: Integrating Mechanistic Efficacy and Global Feasibility Through a Translational Decision Matrix

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P6 - Poster Session 6 (5:00 PM-6:00 PM)

Poster/Presentation
Number 12-009

Objective

To evaluate the clinical efficacy and global feasibility of repurposed drugs for Alzheimer’s disease by integrating cognitive, biomarker, safety, and accessibility data into a translational Efficacy–Feasibility Matrix, identifying candidates that balance mechanistic promise with real-world scalability for equitable, population-level dementia prevention and treatment.

Background Repurposed therapeutics, originally approved for non-Alzheimer’s indications, represent a pragmatic and globally scalable approach to disease modification. While dozens of agents have reached clinical testing, the field lacks an integrated framework to prioritize candidates based on both biological efficacy and implementation feasibility.

Design/Methods We systematically reviewed human Phase 2/3 randomized or controlled trials (2000–2025) of repurposed agents in mild cognitive impairment or Alzheimer’s disease. Drugs were grouped into mechanistic classes (metabolic, vascular, immune, infectious, neurotrophic/synaptic). Each was scored (0–3) for efficacy signal strength (cognition + biomarker outcomes) and feasibility (cost, accessibility, delivery simplicity, safety). These scores populated an Efficacy–Feasibility Matrix to identify high-priority, globally accessible candidates.

Results Among 10 drug classes, metabolic modulators dominated the efficacy axis. GLP-1 receptor agonists (liraglutide, semaglutide) achieved the strongest combined cognitive and biomarker signals (efficacy = 3) but low feasibility (1) due to cost and delivery complexity. Immune stimulation (GM-CSF) also demonstrated short-term biomarker gains but poor accessibility (feasibility = 0). In contrast, metformin, nilvadipine, lithium, and low-dose levetiracetam achieved moderate efficacy (1–2) and high feasibility (2–3), emerging as pragmatic global candidates. Infection-targeted approaches (antibiotics, antivirals) showed transient or mixed benefit yet excellent scalability.

Conclusions Repurposed Alzheimer’s therapeutics occupy distinct translational niches: biologics (GLP-1s, GM-CSF) show strong mechanistic efficacy but limited scalability, while inexpensive oral agents (metformin, lithium, nilvadipine) offer feasible, population-level potential. The Efficacy–Feasibility Matrix provides a novel decision-analytic framework to rank repurposed drugs not only by biological promise but also by their readiness for global implementation, bridging clinical pharmacology with equitable access.

Authors/Disclosures
Salma Younas, PhD, PharmD PRESENTER	Miss Younas has nothing to disclose.
Abhigna Mallepally, MBBS	Abhigna Mallepally, MBBS has nothing to disclose.
SANKRANTHI SARATH CHANDRA, MBBS	Dr. CHANDRA has nothing to disclose.
Aditya Jain, MBBS	Dr. Jain has nothing to disclose.
Aditi Narsinghpura, MBBS	Dr. Narsinghpura has nothing to disclose.
Sweta Sahu	Dr. Sahu has nothing to disclose.

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