Several common medication classes can worsen cognitive function in people with dementia or increase the risk of developing it. The biggest offenders are anticholinergic drugs, benzodiazepines, antipsychotics, and certain sleep aids. Many of these are available over the counter, and some have been prescribed to the same older adults they’re most likely to harm.
Anticholinergic Drugs: The Largest Category
Anticholinergic medications block a chemical messenger called acetylcholine, which nerve cells use to communicate throughout the brain and body. Acetylcholine plays a central role in memory and learning, so drugs that suppress it can directly impair thinking, especially in people whose brains are already vulnerable.
A large case-control study published in The BMJ found that people prescribed anticholinergic drugs with strong activity had an 11% higher odds of developing dementia. The risk climbed with higher doses and longer use, and the association held even when exposure occurred 15 to 20 years before diagnosis. The drug classes most strongly linked to dementia were antidepressants, bladder-control medications, and drugs for Parkinson’s symptoms.
The five most commonly prescribed strong anticholinergics in the study were amitriptyline (a tricyclic antidepressant), dosulepin (another older antidepressant), paroxetine (an SSRI-era antidepressant with anticholinergic properties), oxybutynin (for overactive bladder), and tolterodine (also for bladder control). These aren’t obscure drugs. Millions of older adults take at least one of them.
Over-the-Counter Antihistamines
Diphenhydramine, the active ingredient in Benadryl and many “PM” versions of pain relievers like Tylenol PM and Advil PM, is a strong anticholinergic. A report in JAMA Internal Medicine linked long-term use of diphenhydramine to increased dementia risk. Because these products are sold without a prescription and marketed as harmless sleep aids, many people take them nightly for months or years without realizing the cognitive cost.
Newer antihistamines like loratadine (Claritin) and cetirizine (Zyrtec) work differently and don’t carry the same anticholinergic burden. If you or someone you care for regularly reaches for Benadryl to sleep or manage allergies, these are straightforward swaps worth discussing with a pharmacist.
Benzodiazepines and Anxiety Medications
Benzodiazepines, drugs like lorazepam, diazepam, and alprazolam, are prescribed for anxiety, insomnia, and agitation. In older adults, they’re associated with a 25% to 31% increased risk of dementia at low to moderate cumulative doses. They also cause sedation, falls, and confusion that can look like worsening dementia even when the underlying disease hasn’t changed.
The 2023 American Geriatrics Society Beers Criteria, the most widely used guide for identifying risky medications in older adults, lists benzodiazepines as drugs to avoid in people with dementia or cognitive impairment. The recommendation is rated as strong, based on moderate-quality evidence of harm to the central nervous system.
Sleep Medications Including Z-Drugs
Non-benzodiazepine sleep drugs, often called Z-drugs, include zolpidem (Ambien), eszopiclone (Lunesta), and zaleplon (Sonata). Despite being marketed as safer alternatives to older sedatives, these are also flagged in the Beers Criteria as potentially inappropriate for people with dementia.
Research from UCSF found that people who frequently took sleep medications had a 79% higher chance of developing dementia compared to those who rarely or never used them. The type and quantity of medication appeared to matter, with some sleep aids carrying higher risk than others. Z-drugs and trazodone were among the most commonly used in the study population.
Sleep problems are extremely common in dementia, which creates a difficult cycle: the person needs rest, but many of the drugs that induce sleep also impair cognition. The Alzheimer’s Association recommends trying non-drug strategies first, including maintaining consistent meal and sleep times, getting morning sunlight, exercising during the day (but not within four hours of bedtime), treating underlying pain, and keeping the bedroom dark and comfortable. The FDA has approved suvorexant (Belsomra), which works on the brain’s sleep-wake cycle through a different mechanism, specifically for insomnia in people with mild-to-moderate Alzheimer’s.
Antipsychotics and Mortality Risk
Antipsychotics are sometimes prescribed for agitation, aggression, or hallucinations in people with dementia. They carry the most serious warning of any drug class on this list. In 2005, the FDA added a black box warning to all atypical antipsychotics after clinical trials showed increased mortality in older adults with dementia-related psychosis. In 2008, the warning was extended to older, conventional antipsychotics as well.
Beyond the mortality risk, antipsychotics are associated with a greater rate of cognitive decline and increased stroke risk in people with dementia. The Beers Criteria advises avoiding them for behavioral problems unless non-drug approaches have failed and the person is at risk of harming themselves or others. Even then, the guidance is to use the lowest effective dose and periodically try tapering off to see if the drug is still needed.
Proton Pump Inhibitors: Less Clear Than Headlines Suggest
You may have seen reports linking acid reflux drugs like omeprazole (Prilosec) and esomeprazole (Nexium) to dementia. One observational study published in Neurology found an association between very long-term use (more than 4.5 years) and dementia. But a closer look at the evidence tells a more reassuring story.
A separate study published in Gastroenterology found that in adults 65 and older, proton pump inhibitors were not associated with dementia or cognitive decline over time. The American Gastroenterological Association has stated that patients with a diagnosed condition helped by these drugs should generally stay on them, as the benefits can outweigh the risks. This is a case where the headline outran the science.
Can the Damage Be Reversed?
One of the most important questions families ask is whether cognitive problems caused by these medications improve after stopping them. The honest answer is that researchers are still working this out. Physicians at Indiana University School of Medicine have highlighted the need for clinical trials to determine both the safety of discontinuing these drugs and the degree to which cognitive effects are reversible. Some people do improve after offending medications are tapered, particularly when the drug was causing a reversible fog on top of existing dementia rather than accelerating the disease itself. But the timeline and extent of recovery vary, and stopping certain medications abruptly can cause withdrawal or rebound symptoms.
If you suspect a medication is worsening someone’s thinking or memory, the safest path is a structured review with their prescriber. Pharmacists can also run an “anticholinergic burden” assessment, tallying up the cumulative load from all current medications. In many cases, safer alternatives exist: newer antihistamines instead of diphenhydramine, behavioral strategies instead of sedatives, or lower-risk antidepressants instead of older tricyclics. The goal is reducing the total cognitive burden without leaving symptoms untreated.