The medication group with the strongest and most consistent concern is anticholinergic drugs.
1. Anticholinergic medications — the most important group
Anticholinergic drugs block the action of acetylcholine, a neurotransmitter that is important for memory, learning, attention, and other cognitive functions.
Examples include:
- Bladder medications: oxybutynin, tolterodine, solifenacin, darifenacin
- Some antidepressants: amitriptyline, imipramine, clomipramine, and some other tricyclic antidepressants
- Some antihistamines: diphenhydramine (Benadryl), chlorpheniramine, hydroxyzine
- Some Parkinson’s medications: benztropine, trihexyphenidyl
- Some gastrointestinal antispasmodics
- Certain other medications with significant anticholinergic activity
Long-term/cumulative exposure is the concern—not simply taking one dose occasionally.
A large study of adults ≥55 found that the highest cumulative exposure to strong anticholinergic drugs was associated with approximately 49% higher odds of dementia compared with no exposure. Particularly strong associations were seen with anticholinergic antidepressants, bladder antimuscarinics, antipsychotics, and antiepileptic drugs.
A separate prospective study of adults ≥65 also found that greater cumulative anticholinergic exposure was associated with increased risk of dementia and Alzheimer’s disease.
Why might this happen? Acetylcholine is particularly important to memory circuits. Blocking cholinergic signaling can cause confusion and memory problems immediately, and researchers have proposed that prolonged exposure may contribute to longer-lasting cognitive effects. However, observational studies cannot prove that the medication itself directly causes dementia.
2. Benzodiazepines and related sedative drugs
This is another important group.
Examples include:
- alprazolam (Xanax)
- lorazepam (Ativan)
- clonazepam (Klonopin)
- diazepam (Valium)
- temazepam
- chlordiazepoxide
- some related sleeping medications
Benzodiazepines enhance the activity of GABA, producing sedation, relaxation, and reduced anxiety.
Long-term use has been associated in several studies with:
- memory impairment
- slowed thinking
- attention problems
- confusion
- falls
- dependence and withdrawal problems
- possible increased dementia risk
A meta-analysis found an association between benzodiazepine use and dementia, with estimates ranging from roughly 1.4- to 1.8-fold higher risk in different analyses.
However, this evidence is controversial. Anxiety, insomnia, depression, and early symptoms of dementia can themselves lead people to receive benzodiazepines. This is called reverse causation. A newer 2025 meta-analysis found that chronic benzodiazepine use was not statistically significantly associated with dementia overall (HR 1.17, 95% CI 0.96–1.43).
So I would describe benzodiazepines as a medication group of concern, but not proven to cause dementia.
3. Antipsychotic medications
Examples include:
- risperidone
- olanzapine
- quetiapine
- haloperidol
- clozapine
- aripiprazole
These drugs are sometimes necessary for conditions such as schizophrenia or severe bipolar disorder. They are not medications that should simply be stopped because of dementia concerns.
In older adults, antipsychotics can cause:
- sedation
- slowed cognition
- impaired attention
- movement problems
- orthostatic hypotension
- falls
- stroke and cardiovascular complications
There is particularly strong concern when antipsychotics are given to people who already have dementia for behavioral symptoms. A 2026 systematic review/meta-analysis involving about two million people with dementia found antipsychotic use was associated with increased mortality (pooled HR 1.32).
Importantly, this does not mean antipsychotics necessarily cause dementia in otherwise healthy people. The evidence is stronger for cognitive/adverse effects and serious complications in vulnerable older adults than for proving that antipsychotics initiate neurodegenerative dementia.
4. Certain antidepressants — especially those with anticholinergic effects
Antidepressants are a complicated category because they vary enormously.
Some antidepressants have substantial anticholinergic activity, particularly older tricyclic antidepressants (TCAs) such as:
- amitriptyline
- imipramine
- clomipramine
- doxepin at some doses
Other antidepressants, such as many SSRIs, have considerably less anticholinergic activity.
A systematic review of psychotropic medications in older adults found evidence of cognitive decline with cumulative benzodiazepine exposure and with antidepressant use, particularly antidepressants with anticholinergic properties.
Therefore, it is not accurate to say “all antidepressants cause dementia.” The medication’s individual properties, dose, duration, age of the person, and other medications matter.
5. Bladder antimuscarinic medications
These deserve separate attention because they are a very common source of anticholinergic exposure in older adults.
Examples include:
- oxybutynin
- tolterodine
- solifenacin
- darifenacin
- fesoterodine
They are used for overactive bladder/urinary urgency.
The brain’s cholinergic system is important for memory, and some bladder medications can cross into the central nervous system.
The large 2019 study found particularly strong associations between cumulative use of bladder antimuscarinics and dementia; the highest exposure category had an adjusted OR of 1.65.
A study specifically examining anticholinergic treatment for overactive bladder found that use for ≥3 months was associated with an estimated 46% higher dementia risk compared with nonuse.
Again, these are associations rather than proof of causation.
6. Some antiseizure/antiepileptic medications
This area is much less certain.
Examples include:
- phenobarbital
- carbamazepine
- valproate
- clonazepam
- phenytoin
- gabapentin
- pregabalin
- levetiracetam
- lamotrigine
Some older antiseizure medications can cause significant sedation or cognitive slowing.
A 2023 meta-analysis found a small association between antiseizure medication exposure and dementia overall (OR 1.09), but the association disappeared after adjusting for the reason the medication was prescribed. Associations were observed with some individual drugs, including valproate, carbamazepine, and clonazepam.
This is a good example of why we should not assume that a medication causes dementia simply because people taking it have higher dementia rates. Epilepsy and other conditions for which these medications are prescribed can themselves be associated with dementia.
7. Opioid pain medications
Examples include:
- oxycodone
- hydrocodone
- morphine
- fentanyl
- codeine
- tramadol
Opioids can cause:
- sedation
- impaired attention
- confusion
- delirium
- slowed reaction time
There is increasing research examining whether long-term opioid exposure is associated with dementia. A 2025 systematic review/meta-analysis specifically evaluated this question and noted concerns about prolonged opioid exposure and cognitive health.
However, the evidence is not as established as it is for anticholinergic medications. Chronic pain itself, reduced activity, depression, sleep problems, and other illnesses can also affect dementia risk.
8. Proton-pump inhibitors (PPIs) — a frequently misunderstood group
Examples:
- omeprazole
- esomeprazole
- lansoprazole
- pantoprazole
- rabeprazole
You may have heard that long-term PPI use causes dementia.
Current evidence does not establish that.
Research has produced conflicting results. A 2026 umbrella review of systematic reviews and meta-analyses concluded that most reviews do not find a convincing link between PPI use and dementia, and the authors considered a causal relationship unlikely given the low certainty of the evidence. None of the six reviews examining Alzheimer’s disease found a significant association.
Another meta-analysis of prospective studies found no statistically significant association between PPI use and dementia or Alzheimer’s disease.
So PPIs should not be placed in the same risk category as strong anticholinergic drugs based on current evidence.
A practical ranking
| Medication group | Concern about long-term cognitive effects |
|---|---|
| Strong anticholinergics | 🔴 Strongest concern |
| Benzodiazepines | 🟠 Concern, but causation uncertain |
| Bladder antimuscarinics | 🔴 Important because many are strongly anticholinergic |
| Anticholinergic antidepressants | 🔴 Important |
| Antipsychotics | 🟠 Significant cognitive/safety concerns, especially in dementia |
| Some antiseizure drugs | 🟡 Evidence mixed |
| Long-term opioids | 🟡 Possible association; evidence developing |
| PPIs | 🟢 Current evidence does not establish that they cause dementia |
The most important concept: cumulative anticholinergic burden
A person doesn’t necessarily have to take one “bad” medication. They can take several medications that each have modest anticholinergic effects.
For example, an older person might take:
diphenhydramine + amitriptyline + oxybutynin
Even though these are prescribed for completely different problems, their anticholinergic effects can add together.
This is called anticholinergic burden. Higher cumulative exposure has repeatedly been associated with cognitive decline and dementia in observational research.
Very important: don’t stop these medications abruptly
If you or someone you know takes any of these drugs regularly, don’t stop them suddenly, particularly benzodiazepines, opioids, antidepressants, antipsychotics, or antiseizure medications. Some can cause serious withdrawal or rebound symptoms.
A safer approach is a medication review with a physician or pharmacist, asking:
- Which medications have anticholinergic properties?
- Is each medication still necessary?
- Is there a lower-risk alternative?
- Can the dose be reduced?
- Can any medication be gradually discontinued?
- Are several medications producing the same cognitive side effects?
Also, new confusion or memory problems should not automatically be blamed on medication. Depression, sleep apnea, thyroid disease, vitamin B12 deficiency, infections, hearing/vision problems, strokes, alcohol, metabolic abnormalities, and many other conditions can contribute to cognitive problems.
If you give me the names and doses of the medications you are interested in, I can go through them one by one and explain which ones are anticholinergic, their relative dementia/cognitive risk, and which alternatives are generally considered less problematic