# Nighttime Agitation and Restless Legs Syndrome in People with Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $751,794

## Abstract

Project Summary/Abstract. Nighttime agitation, defined as the appearance or exacerbation of behavioral
disturbances, such as wandering and aggression, in the afternoon and/or evening, is a prevalent symptom in
persons with Alzheimer’s disease that reduces their quality of life and restricts their environments. Effective
treatments are lacking. One major cause for past failure of treatments has been the approach of treating all
nighttime agitation alike. Unlike interventions in the past, our precision medicine approach tailors the
intervention to a specific sleep disorder, restless legs syndrome (RLS). RLS occurs in 10-14% of older adults
and it is likely that persons with Alzheimer’s disease have RLS, since it is quite common, but it is infrequently
identified because diagnosis is dependent on patients answering complex questions about their symptoms.
RLS causes an urge to move associated with uncomfortable and unpleasant leg sensations. The urge to move
and leg discomfort only occur or worsen at night, and relief is by movement. We hypothesized that RLS might
be an etiology for nighttime agitation because: 1) circadian patterns of nighttime agitation and RLS symptoms
are almost identical; 2) unrelieved RLS discomfort may precipitate behaviors such as screaming and requests
for help, and the urge to move may cause wandering, pacing, and restlessness; and 3) factors common in
institutionalized persons with Alzheimer’s disease, such as anemia, prolonged bed rest, and antidepressants,
trigger or worsen RLS. Our preliminary work supports our hypothesis, and provides beginning evidence that
RLS may be an unidentified etiology for nighttime agitation. In 59 persons with dementia and nighttime
agitation, and RLS diagnosed using objective measures, we found that almost ¼ had RLS and that RLS was
associated with nighttime agitation (r = 0.31, p .01). We now propose a pilot clinical trial to determine if RLS
treatment reduces nighttime agitation, improves sleep, reduces antipsychotic medications, and the mechanism
for these effects. We have chosen gabapentin enacarbil (GEn) as the treatment because it is FDA approved for
RLS and has a favorable safety profile. We propose an 8-week, double-blind placebo-controlled randomized
pilot trial of GEn versus placebo in 136 nursing home residents with moderate to severe Alzheimer’s disease,
nighttime agitation, and RLS, followed by an 8-week post-trial evaluation of antipsychotic medication use. The
specific aims are to: 1) Determine the effect of GEn, compared to placebo on nighttime agitation (primary
endpoint); 2) Describe the safety profile of GEn compared to placebo in this population; 3) Estimate the effect
size of GEn compared to placebo on nighttime sleep, RLS behaviors, and antipsychotic medications; 4) Explore
whether frequency of RLS behaviors mediates the effect of GEn on nighttime agitation behaviors. The results
of this study and future definitive trials may shift and improve standards of care for trea...

## Key facts

- **NIH application ID:** 9886167
- **Project number:** 5R01AG051588-06
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Kathy Culpepper Richards
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $751,794
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886167

## Citation

> US National Institutes of Health, RePORTER application 9886167, Nighttime Agitation and Restless Legs Syndrome in People with Alzheimer's Disease (5R01AG051588-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9886167. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*