Understanding Individual Risks, Improving Trial Designs for Sleep Disorders in Alzheimer Disease


Ruth Benca, MD, PhD, a professor and the chair of Psychiatry & Human Behavior at Wake Forest School of Medicine, provided insight on the age- and sex-related differences in sleep disorders, and the needed research on the effects of therapeutics in older populations.

Ruth Benca, MD, PhD, professor and chair of Psychiatry & Human Behavior at the Wake Forest School of Medicine

Ruth Benca, MD, PhD

This is a 2-part interview. Click here for part 1.

Changes in sleep patterns are not uncommon for individuals with Alzheimer disease (AD); however, the reasons why remain a mystery. Sleep disturbances, which tend to get worse over time, may affect up to 25% of people with mild to moderate dementia and 50% of people with severe dementia.1 Excessive daytime sleepiness and insomnia are the more commonly known sleep disorders these patients face, along with a phenomenon called sundowning, where patients’ experience confusion, agitation, anxiousness, and aggressiveness during the evening or night.

If a nondrug approach fails, patients turn to tricyclic antidepressants, such as nortriptyline, or benzodiazepines, such as lorazepam, oxazepam, and temazepam. Although a patient may see benefits from these options, there is hesitancy in how they are prescribed, mainly because of their adverse effect profiles and potential to increase risk of falls and confusion. Ruth Benca, MD, PhD, professor and chair of Psychiatry & Human Behavior at the Wake Forest School of Medicine, believes there needs to be an improved effort to evaluate sleep-inducing and sleep-promoting medications in older adults, especially those with AD or at risk for AD.

At the 2022 SLEEP Annual Meeting, June 4-8, in Charlotte, North Carolina, NeurologyLive® caught up with Benca following a presentation she gave on the impact and management of sleep disorders. In part 2 of the interview, Benca discussed the prevalence of sleep disorders and their associations based on sex and gender, as well as the need to improve and expand clinical trials dedicated to medications for sleep disorders in patients with AD.

NeurologyLive®: Are there subtypes of patients who may be more prone to sleep disorders?

Ruth Benca, MD, PhD: We know that older people have more sleep problems, more insomnia, more other primary sleep disorders than younger people. Women have more insomnia than men and men probably have more apnea than women. There are age and sex-related factors that contribute to sleep problems, which in turn may contribute to Alzheimer disease. One of the things we still need more data on is the impact of treating sleep problems. Just because sleep is an early sign or risk factor, we’re trying to understand how much is causally related. That’s why it’s important to conduct longitudinal studies with well-characterized patients to see if just treating the problem helps.

One of the things that’s probably true is that even if treating sleep problems and sleep disorders helps either mitigate the risk of Alzheimer disease or slow progression, it’s going to be important to do it early. We know that once patients start having significant cognitive impairment or develop Alzheimer disease, you can’t reverse it. What we’re trying to do is see if whether intervening early in those who are high risk helps in the long-term. We’re looking very early in the process in these patients, which might give us some good clues as to where we can have an impact.

How can we overcome the complexities of conducting clinical trials that feature a homogenous set of patients?

For one, we need better tools to describe and assess sleep problems in older adults. Insomnia in an elderly person is probably not the same as insomnia in a 30-year-old, there are a lot of things going on. We don’t have good assessment tools or even questionnaires that are validated in older adults to describe the sleep problems because it’s not just a garden variety of insomnia. They may have trouble sleeping at night, trouble staying awake during the day, they may have wanderings/confusion at night, etc. We need to be able to describe all this. We need to understand if they have sleep apnea, how to treat it, and if we need to be treating it. Again, more data is needed for a lot of these things.

In addition to having better identification, we need to develop better care pathways for older adults at the clinical level. Mostly what we get told for older people and people with Alzheimer disease is what not to do. Most of the medications we use for sleep, particularly the benzodiazepines and benzodiazepine receptor agonists, are on the [American Geriatrics Society’s] Beers criteria of "don’t use these” in older adults. Also, antipsychotics, which are often given to patients with Alzheimer disease, are probably not the safest choice. We tend to over medicate these patients, which may also be contributing. So having good clinical guidelines to assess and treat sleep problems in these patients, at the vest least, are going to improve their quality of life and the quality of life of their caregivers.

We need good, longitudinal studies of treatments. In these patients, there are very few drugs that have been tested in patients with Alzheimer disease, and not a lot that have been tested in older adults. We need more data on the benefits, risks, and side effects, and whether these treatments have any impact on the progression of Alzheimer disease.

In terms of sleep problems in general, we’ve reached a point where both the public and medical practitioners are understanding that sleep is an important pillar of health, yet, that hasn’t been translated into practice. Patients don’t necessarily bring up their sleep problems with their health care providers and health care providers aren’t necessarily doing a good assessment of sleep in their patients. That’s another important message to get across.

Transcript edited for clarity. Click here for more coverage of SLEEP 2022.

1. Alzheimer’s: Managing sleep problems. Mayo Clinic. https://www.mayoclinic.org/healthy-lifestyle/caregivers/in-depth/alzheimers/art-20047832. December 3, 2021. Accessed July 6, 2022.
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