According to the 2025 Alzheimer’s drug development pipeline report, repurposed medications comprise 33% of the Alzheimer's medication pipeline. Because these drugs already have established safety profiles and manufacturing pathways, they can often advance through early clinical development faster, and at lower cost, than entirely novel therapies. Here are several repurposed medications drawing increasing scientific interest for their potential impact on neurocognitive disease.
The vaccine for herpes zoster (aka the shingles vaccine) has mounting evidence for dementia risk reduction.
A leading hypothesis is that the varicella zoster virus that causes shingles contributes to neuroinflammation, amyloid deposition, tau changes, and cerebrovascular damage, while vaccination seems to curb both direct viral effects and trigger broader immune benefits in the aging brain. And best of all, the recombinant zoster vaccine is already recommended for adults 50 and older to prevent shingles, so clinicians can reasonably highlight the potential cognitive benefits when discussing vaccination for its approved indication.
Nucleoside reverse transcriptase inhibitors (NRTIs), used to treat HIV and hepatitis B, are also emerging as potential candidates for Alzheimer's prevention.
A major 2025 study from UVA Health analyzed health insurance records of over 270,000 patients and found that those taking NRTIs had a 6% to 13% lower risk of developing Alzheimer's for every year they were on the medication.
A UT Health San Antonio pilot trial showed patients with mild cognitive impairment taking the NRTI drug lamivudine (3TC) showed improvements in biomarkers of neurodegeneration and brain inflammation at 6 months.
NRTIs appear to block inflammasomes (triggers of harmful brain inflammation) and suppress retrotransposons ("jumping genes") linked to age-related brain damage. A modified compound, K9, in development to deliver the same anti-inflammatory benefits with a safer Alzheimer's-specific profile, is currently being prepared for clinical trials.
While other plaque-targeting drugs act on existing plaques, levetiracetam (used to treat epilepsy) may prevent production of toxic amyloid beta peptides. A recent retrospective analysis from Northwestern found that patients taking levetiracetam experienced a meaningful delay in disease progression compared with patients receiving other medications.
Key caveat: To have an impact, this drug likely needs to be taken up to 20 years before symptom onset, so experts are considering prophylactic use in high-risk populations (i.e. those with genetic predisposition and/or Down syndrome). Improved longer-acting formulations are now in development.
Drug |
Original Use |
Suspected Alzheimer's Mechanisms |
Status |
|
Metformin |
Type 2 diabetes |
Neuroprotective effects on metabolism, inflammation, and brain insulin signaling |
Phase 2b/3 trials underway |
|
Sildenafil |
Erectile dysfunction |
Nerve protection, improved cerebrovascular flow, reduced tau |
Prospective trials underway |
|
Riluzole |
ALS |
Prevents or slows decline of brain glucose metabolism |
Established safety profile supports accelerated human trials |
The popular diabetes and weight loss medication semaglutide was expected to have a significant disease-modifying effect on Alzheimer's, but in November 2025 Novo Nordisk announced that the medication did not significantly slow Alzheimer's progression in the EVOKE and EVOKE+ Phase 3 trials. On the other hand, both trials showed improvements in some Alzheimer's-related biomarkers. Researchers contend that GLP-1 drugs may still have a role—potentially earlier in the progression of the disease. Trial data analysis and more research is ongoing.
Similarly, lithium made headlines in September 2025 when a study in Nature found striking differences in naturally occurring levels of lithium in the brains of people with Alzheimer's and MCI. Yet a small trial recently published in JAMA Neurology showed that compared with placebo, two years of lithium carbonate treatment had no impact on cognition or brain atrophy. Research into alternative lithium formulations, including lithium orotate, is ongoing.
Alzheimer’s increasingly appears to be a multi‑pathway disease, and future treatment will likely require combination approaches targeting inflammation, vascular health, protein aggregation, and metabolic dysfunction. The pipeline has never been broader, and repurposed drugs—with foundational safety work already done—are its fastest-moving segment. Even negative results, as with the EVOKE trials, help refine patient selection and inform the future research.
For clinical leaders: Connect your patients to trials via the Alzheimer's Association TrialMatch.
For patients and caregivers: Talk to your doctor before considering any off-label use of the medications described here.
As medications become more effective in modifying or delaying progression, making sure impaired patients are flagged early is priority number one. Routine cognitive screening has never been more important, and it’s smart to question whether your current tools are up to the challenge. Leading healthcare organizations, like Northern California's Sutter Health, are building innovative new workflows around Neurotrack’s quick digital assessments to triage patients on existing wait lists and identify early symptoms in their 65+ population.
Sign up to get a detection gap audit and a walkthrough of Neurotrack's platform.