March 2, 2021 Harvard Health Publishing – Harvard Medical School

Two common classes of drugs have been linked to dementia. Fortunately, there are alternatives to both.

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If you’re worried about developing dementia, you’ve probably memorized the list of things you should do to minimize your risk—eating a healthy diet, exercising regularly, getting adequate sleep, and keeping your mind and soul engaged. In addition, some of the drugs you may be taking to help you accomplish those things could increase your risk of dementia. In two separate large population studies, both benzodiazepines (a category that includes medications for anxiety and sleeping pills) and anticholinergics (a group that encompasses medications for allergies and colds, depression, high blood pressure, and incontinence) were associated with an increased risk of dementia in people who used them for longer than a few months. In both cases, the effect increased with the dose of the drug and the duration of use.

These findings didn’t come entirely as a surprise to doctors who treat older people. The Beer’s List, published by the American Geriatrics Society, has long recognized benzodiazepines, antihistamines, and tricyclic antidepressants as potentially inappropriate for older adults, given their side effects. Such drugs are on the list because they share troubling side effects—confusion, clouded thinking, and memory lapses—that can lead to falls, fractures, and auto accidents.

What the studies found

It’s important to note that neither of these studies was a randomized controlled clinical trial, so neither proved that either type of drug causes dementia.

The anticholinergic study. Researchers tracked nearly 3,500 men and women ages 65 or older who took part in Adult Changes in Thought (ACT), a long-term study conducted by the University of Washington and Group Health, a Seattle health care system. They used Group Health’s pharmacy records to determine all the drugs, both prescription and over-the-counter, that each participant took in the 10 years before starting the study. Participants’ health was tracked for an average of seven years. During that time, 800 of them developed dementia. When the researchers examined medication use, they found that people who used anticholinergic drugs were more likely to have developed dementia than those who didn’t use them. Moreover, dementia risk increased along with the cumulative dose. Taking an anticholinergic for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.

The University of Washington study is the first to include nonprescription drugs. It is also the first to eliminate the possibility that people were taking the drugs to alleviate early symptoms of undiagnosed dementia. For people who took anticholinergic bladder medications, the increased risk was just as high as for those taking tricyclic antidepressants, which are also anticholinergics.

The benzodiazepine study. A team of researchers from France and Canada linked benzodiazepine use to an increased risk of being diagnosed with Alzheimer’s disease. In the study, the greater people’s cumulative dose of benzodiazepines, the higher their risk.

The researchers relied on a database maintained by the Quebec health insurance program. From it, they identified nearly 2,000 men and women over age 66 who had been diagnosed with Alzheimer’s disease. They randomly selected more than 7,000 others without Alzheimer’s who were matched for age and sex to those with the disease. Once the groups were set, the researchers looked at the drug prescriptions during the five to six years preceding the Alzheimer’s diagnosis.

People who had taken a benzodiazepine for three consecutive months or less had about the same dementia risk as those who had never taken one. But those who had taken a benzodiazepine for three to six months had a 32% greater risk of developing Alzheimer’s, and those taking one for more than six months had an 84% greater risk than those who hadn’t taken one.

The type of drug taken also mattered. People who were on a long-acting benzodiazepine like diazepam (Valium) or flurazepam (Dalmane) were at greater risk than those on a short-acting one like triazolam (Halcion), lorazepam (Ativan), alprazolam (Xanax), or temazepam (Restoril).

Why these drugs have a stronger effect in older peopleAs we age, our ability to process medication changes. The kidneys and liver clear drugs more slowly, so drug levels in the blood remain higher for a longer time. People also gain fat and lose muscle mass over time. Both these changes affect the way drugs are distributed to and broken down in body tissues. And because these drugs are stored in body fat, they can continue to produce effects days after people stop taking them, especially in people with a higher proportion of body fat. In addition, older people tend to take more prescription and over-the-counter medications, each of which has the potential to suppress or enhance the effects of the others.

Why the drugs affect your mind

Both anticholinergics and benzodiazepines affect the activity of neurotransmitters—chemical messengers that work in the central nervous system—but the drugs work in slightly different ways.

Anticholinergic drugs block the action of acetylcholine. In the brain, acetylcholine is involved in learning and memory. In the rest of the body, it stimulates the autonomic nerves—those that regulate contractions of blood vessels, airways, and our cardiovascular and digestive systems. The strongest anticholinergic drugs include some antihistamines, tricyclic antidepressants, medications to control overactive bladder, and sleeping pills.

Benzodiazepines boost another neurotransmitter’s effectiveness. They make gamma-aminobutyric acid (GABA)—which slows the activity of neurons in the brain-—more potent. For that reason, they are used to calm anxiety and help people sleep.

If you take one of these drugs

It’s always good to review the potential benefits and harms of these medications with your doctor. If a drug appears problematic, the two of you can explore alternatives by considering the reason it was prescribed and seeing if there is a different type of drug that can be used as a replacement.

Don’t stop taking the drugs on your own. It isn’t safe to quit most benzodiazepines and anticholinergic drugs “cold turkey.” Work with your clinician to develop a plan for tapering off them.

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