6 drugs linked to an increased risk of dementia (some of them may surprise you)
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We know that some drugs are linked to dementia risk, especially with long-term or high-dose use, but causality is not proven for most associations.
—Katie Henn, PharmD
Whether dementia progresses after medication discontinuation, or is reversible, remains a clinically and mechanistically complex question.
—Mariya Kotova, PharmD
Gabapentin has come under scrutiny for its association with increased risk of dementia. [] But it’s not the only medication linked to an increased risk.
“We know that some drugs are linked to dementia risk, especially with long-term or high-dose use, but causality is not proven for most associations. Probable mechanisms include direct neurotoxicity, disruption of neurotransmitter systems (notably acetylcholine), and indirect effects via vascular or metabolic changes,” Katie Henn, PharmD, a clinical pharmacist at the University of Kansas Medical Center’s Parkinson’s Disease and Movement Disorders Clinic, tells MDLinx.
“The strongest evidence is for anticholinergic drugs (eg, tricyclic antidepressants), antihistamines (eg, over-the-counter products like diphenhydramine), [and] bladder antimuscarinics. Other classes, including benzodiazepines, proton pump inhibitors, and gabapentinoids, show associations in observational studies, but causality remains uncertain,” Dr. Henn adds.
Mechanisms behind the risk
While causality is difficult to prove, experts say there could be a number of different mechanisms that contribute to an increased risk of dementia with certain medications.
These include delirium acceleration in vulnerable patients, chronic anticholinergic burden, persistent central nervous system depression, reduced cognitive reserve due to sedation, inactivity, and sleep disruption.
“Importantly, some drugs may unmask or accelerate underlying neurodegeneration rather than cause it de novo," Sean Mackey, MD, PhD, chief of the division of Stanford Pain Medicine, tells MDLinx.
With a variety of medications potentially being associated with an increased risk of dementia, experts say physicians can take several steps to reduce potential risk.
“Clinicians should use the lowest effective dose and limit duration, particularly for medications known or suspected to increase dementia risk. Regular medication review and deprescribing, when clinically appropriate, are key strategies to reduce cumulative harm, especially from polypharmacy and anticholinergic burden,” Dr. Henn tells MDLinx.
Dr. Henn continues: “When possible, safer pharmacologic alternatives or nonpharmacologic therapies should be considered. Ongoing monitoring for cognitive changes (eg, 3–6 months after initiation, and annually thereafter) can help identify emerging adverse effects early and support individualized, risk-balanced care."
Research into the risks of certain medications and dementia is ongoing, and experts say more research is needed to accurately determine the level of risk and whether it can be slowed or reversed.
“Whether dementia progresses after medication discontinuation, or is reversible, remains a clinically and mechanistically complex question,” Mariya Kotova, PharmD, a pain management pharmacist at UC Davis Health, tells MDLinx.
Related: Common conditions that raise dementia riskA multidisciplinary approach protects patients
In the meantime, pharmacists say a team-based strategy is the best way to keep patients safe.
“A multidisciplinary team approach can play a crucial role in reducing medication‑related cognitive harm, with pharmacists uniquely positioned to support this effort,” Dr. Henn says.
“Pharmacists contribute through comprehensive medication reviews, identification of high‑risk and potentially inappropriate medications, and facilitation of deprescribing in collaboration with prescribers,” Dr. Henn adds.