Every week in my Palm Beach practice, a patient’s adult child asks me some version of the same question: “Is my parent’s medication making their memory worse — or could it actually be raising their risk of Alzheimer’s?” It’s a fair question, and increasingly, the science says yes to both. Dementia risk isn’t fixed by genetics alone. A growing body of research — including a major 2024 update from the Lancet Commission on Dementia Prevention — shows that nearly half of all dementia cases may be preventable or delayed by addressing modifiable medication, lifestyle, and health factors across the lifespan.
A Composite Case: “Ruth,” Age 74
Ruth (a composite patient reflecting patterns I see often, not a real individual) came to see me after her daughter noticed she was repeating herself and seemed “foggier” than a year earlier. Her medication list told most of the story before we even ran cognitive testing: diphenhydramine (Benadryl) nightly for sleep, oxybutynin for overactive bladder, and alprazolam as-needed for anxiety that had quietly become daily. Each of these medications, taken alone, seemed reasonable to the prescribers who started them. Taken together over years, they represented a significant cumulative anticholinergic and sedative burden — exactly the pattern the research below describes.
Medications Linked to Increased Dementia Risk
Anticholinergic Medications
This is the class with the strongest and most consistent evidence. Anticholinergics block acetylcholine, a neurotransmitter already depleted in Alzheimer’s disease. A landmark case-controlled study of nearly 300,000 medical records found that people taking an anticholinergic medication daily for three or more years had roughly a 50% increased risk of developing dementia, with antidepressants, antipsychotics, Parkinson’s medications, epilepsy drugs, and bladder medications carrying the highest risk. A pooled analysis of over 1.5 million people across 14 studies confirmed the association with both all-cause dementia and Alzheimer’s disease specifically.
Common anticholinergic culprits include first-generation antihistamines (diphenhydramine, hydroxyzine), tricyclic antidepressants (amitriptyline, nortriptyline), bladder antispasmodics (oxybutynin), and certain muscle relaxants. Many are available over-the-counter, so patients often don’t realize they’re accumulating anticholinergic burden from sleep aids or allergy pills alongside prescribed medications.
Benzodiazepines
Long-term benzodiazepine use — alprazolam (Xanax), lorazepam (Ativan), and diazepam (Valium) among the most frequently implicated — has been associated with elevated dementia risk in multiple cohort studies, likely through disrupted sleep architecture and interference with memory consolidation. A UK cohort study using the Medical Research Council Cognitive Function and Ageing Study data reinforced this signal and recommended avoiding long-term anticholinergic and benzodiazepine prescribing in older adults specifically.
Antipsychotics
Emerging research on olanzapine, risperidone, and clozapine suggests these medications may carry drug-specific effects on microglial phagocytosis — the brain’s immune housekeeping process — that could contribute to Alzheimer’s pathology beyond their general anticholinergic activity. This is an active area of investigation, but it reinforces the importance of using antipsychotics at the lowest effective dose for the shortest necessary duration, particularly in older adults.
Opioids and Other Medications Under Study
Prospective cohort data has linked prescription opioid use to cognitive decline risk. Proton pump inhibitors (PPIs) have been studied extensively with mixed results — some claims-data analyses show an association with dementia, while more recent umbrella reviews of the pooled evidence have been less conclusive, so this remains a genuinely unsettled question rather than an established risk. Notably, metformin has NOT been shown to increase dementia risk — in fact, some data suggest people with diabetes on metformin have lower dementia rates, which is a helpful reassurance for the many patients who ask about it.
Clinical Research Note
The 2025 AgeWell.de randomized study tested whether structured deprescribing counseling for anticholinergic medications in at-risk older adults could improve outcomes — reflecting a broader shift in geriatric and psychiatric practice toward proactive medication review as a dementia prevention strategy, not just a side-effect management tool.
The 14 Modifiable Lifestyle Risk Factors
The 2024 Lancet Commission on Dementia Prevention, Intervention, and Care — the most authoritative synthesis of this evidence to date — identified 14 modifiable risk factors spanning early life through old age. Addressing all 14 could theoretically prevent or delay up to 45% of dementia cases worldwide.
Early life: Less access to education.
Midlife (newly reclassified in 2024): Hearing loss, high LDL cholesterol, depression, traumatic brain injury, physical inactivity, diabetes, smoking, hypertension, obesity, and excessive alcohol consumption.
Later life: Social isolation, air pollution exposure, and untreated vision loss (the newest addition to the 2024 list, alongside high LDL cholesterol).
Notably, the Commission found that smoking, depression, physical inactivity, and diabetes exert more of their damaging effect in midlife than previously thought — meaning intervention needs to start well before a patient’s 60s or 70s to have maximum benefit. Hearing loss deserves particular attention: it’s one of the largest single contributors to attributable dementia risk, and it’s also one of the most treatable, since hearing aids are a low-friction intervention many patients simply haven’t been encouraged to pursue.
Where This Leaves Ruth — and Your Loved Ones
For Ruth, the plan wasn’t dramatic — it was methodical. We tapered the alprazolam with a slow benzodiazepine taper protocol, switched her nighttime antihistamine to a non-anticholinergic sleep strategy, and referred her to urology to discuss a beta-3 agonist alternative to oxybutynin for her bladder symptoms, which carries a meaningfully lower dementia signal in comparative cohort studies. We also addressed her untreated hearing loss and got her walking daily with a friend, tackling both a medication risk and two of the Lancet Commission’s modifiable lifestyle factors at once.
The larger point for any patient or family member reading this: dementia risk is not simply inherited and immutable. A significant portion is shaped by decisions that are entirely reviewable — what’s in the medicine cabinet, whether hearing and vision are corrected, how blood pressure and cholesterol are managed, and how connected and active a person remains. An annual medication review focused specifically on anticholinergic and sedative burden is one of the highest-yield, lowest-cost interventions available in preventive psychiatry today.
Concerned About Medications and Cognitive Health?
Dr. Mark Agresti provides integrative psychiatric evaluation and medication review for patients and families throughout Palm Beach and statewide Florida via telemedicine, with a focus on identifying and reducing modifiable dementia risk factors.
Mark G. Agresti MD LLC | 44 Cocoanut Row, Suite M202, Palm Beach, FL 33480 [(561) 760-4107](tel:(561) 760-4107) | [email protected]
Keywords: Alzheimer’s risk factors, dementia prevention Palm Beach, anticholinergic medications dementia, benzodiazepines memory loss, Lancet Commission dementi