Restless Legs Syndrome Foundation Blog

Nighttime Agitation — Is It RLS?

By Kathy Richards, PhD, RN, FAAN; member of the RLS Foundation’s Scientific and Medical Advisory Board

For people in the dementia stage of Alzheimer’s disease (AD-D), the problem of nighttime agitation, defined as the presence or worsening of behaviors such as aggression or wandering in the afternoon or evening, is a management challenge for their caregivers. This problem often leads to more and more restrictive living environments for persons with AD-D, including placement in nursing homes. In addition to AD-D, nighttime agitation might be a manifestation of a common neurologic condition: restless legs syndrome (RLS). Symptoms of RLS match those of nighttime agitation – that is, not being able to remain still, and experiencing symptoms in the evening.

In a recent study published in the Journal of Post-Acute and Long-Term Care Medicine, the characteristics and behaviors of 76 older adults with AD-D, nighttime agitation, and newly diagnosed RLS were measured. RLS was diagnosed using the Behavioral Indicators Test – Restless Legs, a validated tool for diagnosis of RLS in persons with AD-D. The individuals in the study were unable to cognitively and verbally report their RLS symptoms. The older adults with AD-D were also observed for nighttime agitation behaviors. Assessment of iron status and sleep quality (using motion sensors) was conducted for these patients as well. The researchers found that fewer minutes of documented sleep and lower transferrin (iron) saturation were associated with more frequent behaviors of nighttime agitation. Over three-quarters of the patients with RLS and nighttime agitation had been prescribed medications that worsen RLS, such as antihistamines and serotonin reuptake inhibitors.

These findings support clinical consideration of nighttime agitation as a sign of RLS and highlight the need for further research to identify new management strategies. The findings also suggest that medical providers should take steps to identify and diagnose RLS; treat iron deficiency anemia if indicated by low transferrin saturation; and deprescribe medications that worsen RLS. The combination of these strategies will lead to a reduction in any RLS component of nighttime agitation in patients with AD-D. In addition, it is recommended that nursing homes change common practices that are likely to worsen RLS discomfort and nighttime agitation, such as restricting residents from evening walking and putting them to bed early.

Kathy Richards, PhD, RN, FAAN, is a research professor at The University of Texas at Austin, School of Nursing. As a UT Austin PhD graduate, Kathy has conducted sleep research in Alzheimer's disease for 20 years, and received over $25 million in NIH funding to support her research endeavors. Her recent project is the NightRest project and the Behavioral Indicators Test for Restless Legs Syndrome in older adults. In partnership with Christine Kovach, PhD, RN, FAAN, Richards received a $3.9 million five year grant from the National Institute on Aging to improve the treatment of nighttime agitation in those with Alzheimer's disease. They hypothesize that RLS may be a cause for nighttime agitation and sleep disturbance in these individuals. This study marks the very first time that a new diagnostic tool will be used in research on nighttime agitation.

For many people who have Alzheimer’s disease, evenings are difficult. Right around sundown, uneasy feelings and confusion start to flow. The person may become forgetful, agitated – even aggressive, and start pacing or wandering. These symptoms can last through the night and make it tough for anyone in the household to get a good night’s sleep.

Could it be that these behaviors – known as nighttime agitation, or “sundowning” – are caused by RLS? And could treating the RLS lessen the nighttime agitation symptoms?

Researchers led by Kathy Richards, PhD, at the University of Texas at Austin are working to answer these questions. Dr. Richards and co-investigator Christine Kovach, PhD, from the University of Wisconsin-Milwaukee have been awarded a $3.9 million, five-year grant from the National Institute on Aging to evaluate whether there is an association between nighttime agitation and RLS in people who have Alzheimer’s disease.

“Nighttime agitation is the No. 1 reason why people with Alzheimer’s cannot be cared for at home,” says Dr. Richards. “If we can find a better and more precise way to treat nighttime agitation, we can improve the quality of life for many persons who are living with Alzheimer’s disease.”

Nighttime agitation is often treated with powerful antipsychotic drugs, which are only moderately effective and carry with them serious risks, such as falls, stroke and death.

Because nighttime agitation has a strong circadian component and shares symptoms with RLS, Dr. Richards and others have long postulated that for some people, undiagnosed RLS could be the underlying cause. In a previous study led by Dr. Richards, researchers examined symptoms in 59 people who had Alzheimer’s disease and nighttime agitation. They found that 24 percent of participants also had RLS.

In the current research, the team will validate this result in a pilot study – an eight-week, double-blind, randomized controlled trial with 136 long-term care residents who have nighttime agitation and RLS. Participants will receive either gabapentin enacarbil (Horizant, an FDA-approved medication for treating RLS) or a placebo. Data from the study will also help discern the effectiveness, safety and optimal dosage of gabapentin enacarbil for treating nighttime agitation, as well as whether the frequency of RLS symptoms may be linked to nighttime agitation.

The researchers will use a tool newly developed by Dr. Richards called the Behavioral Indicators Test-Restless Legs. This test includes a brief 20-minute observation and simple set of questions for caregivers. Previous studies have shown the tool to be an effective way to diagnose RLS in people who have Alzheimer’s, and one that has potential for future use with children and others who don’t have the ability to report their symptoms.

RLS Foundation Executive Director Karla Dzienkowski visited the University of Texas in May, where she gave a presentation about RLS and met with Dr. Richards’ team to extend the RLS Foundation’s support for the research endeavor. “Cognitively impaired seniors with RLS may have difficulty expressing RLS symptoms causing an inability to sit or lie still during the evening or nighttime hours,” says Dzienkowski. “This study will ensure seniors with cognitive impairments are accurately diagnosed and receive proper treatment to manage their RLS symptoms.”

Dr. Richards emphasizes that while there is no evidence suggesting that RLS causes Alzheimer’s, the study may show that it’s important for caregivers of people with any type of dementia to watch for possible signs of RLS that can then be treated to potentially reduce nighttime agitation.

It all comes down to quality of life for people who have dementia, says Richards. “I hope they will be more comfortable, and that they – and their caregivers – can get a good night’s sleep.”

Kathy Richards, PhD, is a member of the RLS Foundation Scientific and Medical Advisory Board. Read more about her research on the University of Texas at Austin School of Nursing newsletter.