As we strive to maintain our health and well-being, it's important to understand how different medications can affect our long-term cognitive function. Many commonly prescribed and over-the-counter drugs offer effective treatment for specific conditions but may also raise your risk of dementia later in life. Researchers continue to focus on this critical connection, and staying informed helps you have more productive conversations with your healthcare provider.
The following guide offers a detailed overview of several classes of medications that research links to a higher risk of dementia. You will find what these drugs treat, the evidence connecting them to cognitive decline, and what these findings mean for you. By sharing this knowledge, we aim to help you partner with your doctor and make proactive choices for your health.
Understanding the Link: Anticholinergic Drugs
Many of the medications discussed here fall under the category of anticholinergics. These drugs block acetylcholine, a key neurotransmitter that supports memory, learning, and muscle function. By interfering with acetylcholine, anticholinergic drugs can cause short-term side effects like confusion, blurred vision, and memory loss. More concerning, people who use these medications long-term face a greater risk of developing dementia.
A landmark study published in JAMA Internal Medicine tracked nearly 3,500 individuals aged 65 and older for over seven years. The researchers found that people who used strong anticholinergic medications more frequently had a significantly higher risk of dementia.
Let's examine some of these specific medications.
Diphenhydramine (Benadryl)
What It Treats:
Diphenhydramine, a first-generation antihistamine, has a widespread presence in over-the-counter products such as Benadryl for allergies, Tylenol PM, ZzzQuil for sleep, and Dramamine for motion sickness. People rely on it to address allergic reactions, cold symptoms like sneezing and runny nose, and insomnia.
How It Might Increase Dementia Risk:
Diphenhydramine, a potent anticholinergic, crosses the blood-brain barrier and directly impacts cognitive function. By blocking acetylcholine receptors in the brain, it produces immediate effects like drowsiness and confusion. Ongoing, long-term use can change the brain’s structure and function in lasting ways. The cumulative effect of blocking acetylcholine may speed up the pathways that lead to dementia and Alzheimer’s disease. Since the medication is easy to access without a prescription, the risk of unintentional overuse is especially high.
Amitriptyline
What It Treats:
Amitriptyline, a tricyclic antidepressant (TCA), once served as a primary option for depression. Today, doctors more often prescribe it in lower doses for nerve pain (neuropathy), fibromyalgia, migraine prevention, and insomnia.
How It Might Increase Dementia Risk:
Amitriptyline has strong anticholinergic effects. Like diphenhydramine, it interferes with acetylcholine in the brain, disrupting memory consolidation and other cognitive processes. The same mechanism that relieves pain and promotes sleep also harms cognition. Research on antidepressants indicates that older tricyclics like amitriptyline create greater dementia risk compared to newer SSRIs, such as Prozac and Zoloft, which lack significant anticholinergic activity.
Oxybutynin (Ditropan) and Tolterodine (Detrol)
What They Treat:
Doctors prescribe oxybutynin and tolterodine for overactive bladder (OAB), a condition marked by frequent and urgent needs to urinate. These medications relax bladder muscles and help reduce urgency and frequency.
How They Might Increase Dementia Risk:
These drugs exhibit strong anticholinergic properties as they block acetylcholine’s effect on the bladder. Because they are not fully selective for only bladder receptors, they also affect the brain. The JAMA Internal Medicine study specifically linked high-dose bladder antimuscarinics, including oxybutynin, to nearly a 50% increase in dementia risk. In recent years, safer alternatives with lower anticholinergic effects have become available for OAB management.
Benzodiazepines: A Class of Concern
Doctors often prescribe benzodiazepines for anxiety, insomnia, panic attacks, and seizures. These drugs enhance the effect of GABA, a neurotransmitter that lowers brain activity to produce a calming effect. Although benzodiazepines can effectively treat certain symptoms in the short term, researchers continue to investigate their long-term consequences for cognitive health.
Alprazolam (Xanax), Lorazepam (Ativan), and Diazepam (Valium)
What They Treat:
- Alprazolam (Xanax): Used for anxiety and panic disorders, especially acute panic attacks due to fast action.
- Lorazepam (Ativan): Manages anxiety, insomnia, and occasionally prepares patients for surgery by reducing anxiety.
- Diazepam (Valium): Treats anxiety, muscle spasms, and seizures through longer-lasting effects.
How They Might Increase Dementia Risk:
Several large-scale studies establish a connection between long-term benzodiazepine use and dementia. For example, the British Medical Journal followed 1,700 people with Alzheimer’s disease and found that individuals who took benzodiazepines for three months or more had up to a 51% higher risk of developing dementia.
Experts have proposed multiple explanations for this association. Prolonged benzodiazepine use may impair cognitive function, and this impairment does not always reverse after discontinuation. Additionally, the sedative effects can reduce activity levels, another risk factor for dementia. Sometimes, clinicians prescribe benzodiazepines for early dementia symptoms, such as anxiety and sleep difficulties, which complicates determining whether the drug or the underlying condition leads to cognitive decline. Healthcare providers widely recommend using benzodiazepines for the shortest duration possible.
Proton Pump Inhibitors (PPIs)
Proton pump inhibitors figure among the most frequently prescribed drugs worldwide, intended to lower stomach acid for conditions like acid reflux, GERD, and ulcers.
Omeprazole (Prilosec) and Esomeprazole (Nexium)
What They Treat:
Both medications, available over-the-counter and by prescription, block stomach acid-producing enzymes and provide relief from heartburn and esophagitis caused by reflux.
How They Might Increase Dementia Risk:
Discoveries around PPIs and dementia risk remain relatively new and somewhat inconsistent. One notable German study noted a 44% higher dementia risk among regular PPI users compared to non-users. Researchers theorize that PPIs may interfere with the body’s ability to break down amyloid proteins in the brain—a process crucial in preventing Alzheimer’s disease.
Another theory proposes that PPIs inhibit proper vitamin B12 absorption by reducing stomach acid, resulting in deficiency. Low vitamin B12 levels can mimic or intensify dementia-like symptoms. While the research remains inconclusive, these concerns highlight the importance of avoiding unnecessary long-term PPI use.
Corticosteroids
Corticosteroids, also known as “steroids,” deliver strong anti-inflammatory effects by mimicking cortisol, a hormone that the adrenal glands naturally produce.
Prednisone and Hydrocortisone
What They Treat:
Doctors use corticosteroids to treat widespread inflammation in conditions such as rheumatoid arthritis, lupus, severe allergies, asthma, or skin irritations like eczema. You might take prednisone orally, while hydrocortisone usually comes as a topical cream.
How They Might Increase Dementia Risk:
Corticosteroids can alter the brain’s structure and function, particularly in the hippocampus, a region that manages memory. Prolonged exposure to high cortisol levels, whether through chronic stress or steroid use, may shrink the hippocampus and impair function.
A Dutch study published in BMJ Open tracked thousands of people and found changes in brain white matter and reduced brain volume among systemic steroid users. While these medications can save lives, years of regular use may make the brain more susceptible to cognitive decline. Risks rise especially with long-term, systemic administration as opposed to short-term or topical application.
Antipsychotics
Doctors mainly prescribe antipsychotics to treat schizophrenia and other forms of psychosis. Some also use them off-label for managing behavioral symptoms, such as agitation or aggression, in people with dementia.
Haloperidol and Risperidone
What They Treat:
- Haloperidol: Addresses psychotic disorders, tics, and vocal outbursts (for example, in Tourette’s syndrome).
- Risperidone: Used for schizophrenia, bipolar disorder, and irritability in autism.
How They Might Increase Dementia Risk:
Prescribing antipsychotics to older adults poses special risks, especially for those living with dementia. The FDA places a “black box” warning on these medications, as they can increase mortality among seniors with dementia-related psychosis.
Moreover, substantial evidence shows that antipsychotics speed up cognitive decline. They block dopamine receptors and, like anticholinergics, disrupt brain functions associated with memory and learning. A large Finnish study found that dementia patients taking antipsychotics experienced cognitive decline more rapidly than those who did not use these drugs. Based on this risk, doctors urge using antipsychotics cautiously and only as a last resort for behavioral symptoms in dementia.
Opioids
Opioid painkillers provide powerful relief for severe pain but carry a high risk of addiction, side effects, and cognitive complications.
Morphine and Hydrocodone
What They Treat:
- Morphine: Relieves severe pain, frequently after surgery or in advanced cancer care.
- Hydrocodone: Appears in pain relievers like Vicodin and Norco to help with moderate to severe pain.
How They Might Increase Dementia Risk:
Opioids can cause acute confusion and delirium, and chronic use may harm the brain through several mechanisms. Long-term opioid use can decrease oxygen supply to the brain (hypoxia), which damages neurons. Additionally, findings suggest that opioids trigger inflammation in the brain and weaken the blood-brain barrier—both associated with an increased risk of developing Alzheimer’s disease. At recent Alzheimer’s Association International Conferences, researchers highlighted the higher dementia risk in older adults using opioids chronically.
Taking Control of Your Health: Next Steps
Learning that you may face dementia risks from certain medications can be unsettling, especially if you rely on these drugs for chronic conditions. However, remember the distinction between association and causation—never stop any prescribed medication without first consulting your healthcare provider.
Use this information as a springboard to open conversations with your doctor. Practical steps include:
- Schedule a Medication Review: Meet with your doctor or pharmacist to review all your medications, including over-the-counter products and supplements.
- Discuss Dementia Risks: Share your concerns and ask about any medications with high anticholinergic effects or other dementia-related risks.
- Clarify the Reason for Each Drug: Make sure you know why you take every medication. Ask if you still need a treatment or if your condition has changed.
- Ask About Alternatives: Inquire about safer therapies. For instance, try newer, non-anticholinergic antihistamines for allergies, or consider physical therapy instead of painkillers when possible.
- Aim for the Lowest Effective Dose: If you need to continue a medication, work with your doctor to use the smallest effective dose for the shortest duration possible.
Think of your health as a lifelong partnership between you and your medical team. By staying informed and taking an active role, you help safeguard both your physical and cognitive well-being for years ahead.
