Nighttime Agitation in Persons with Dementia as a Manifestation of Restless Legs Syndrome.

OBJECTIVES: Nighttime agitation or "sundowning" is challenging for clinicians and caregivers to manage in older adults in the dementia stage of Alzheimer's disease (AD-D). Our research previously revealed that nighttime agitation might be a manifestation of restless legs syndrome (RLS). The current study aims to describe the characteristics of older adults with AD-D, nighttime agitation, and RLS, and to evaluate sleep disturbance and iron status in relation to nighttime agitation severity. DESIGN: An observational study with baseline descriptive and correlational data from a clinical trial. SETTING AND PARTICIPANTS: Long-term care (n = 69) and independent living (n = 7); age 82.91 ± 9.46 years, with AD-D, nighttime agitation, and RLS. MEASUREMENTS: Trained observers counted nighttime agitation behaviors. Independent variables were age; cognition measured by the Mini-Mental State Examination; minutes slept from actigraphy; transferrin saturation percentage (TS%) and transferrin from fasting blood samples; and illness severity using the Cumulative Illness Rating Scale for Geriatrics. Bivariate and multivariable linear regression models were generated. RESULTS: In the multivariable model, sleep minutes (P = .002) and TS% (P = .003) were negatively associated with frequency of nighttime agitation behaviors, and they explained 20% of the variance. Seventy-nine percent received 1 or more medications that worsen RLS symptoms, such as antihistamines and serotonin reuptake inhibitors. CONCLUSIONS AND IMPLICATIONS: We encourage clinicians to consider nighttime agitation as a manifestation of RLS. Treatment of iron deficiency indicated by low TS% and deprescribing medications that exacerbate RLS may decrease nighttime agitation, improve sleep, and enhance quality of life in older adults with AD-D.

Nighttime Agitation and Restless Legs Syndrome in Persons With Alzheimer's Disease: Study Protocol for a Double-Blind, Placebo-Controlled, Randomized Trial (NightRest).

Nighttime agitation is a prevalent symptom in persons with Alzheimer's disease (AD). Effective treatments are absent due to our limited knowledge of its etiology. We hypothesized that restless legs syndrome (RLS), a common neurological sensorimotor disorder of uncomfortable leg sensations that appear at night and interfere with sleep, might be a cause for nighttime agitation in persons with AD. RLS is infrequently identified in persons with AD because traditional diagnosis is dependent on patients answering complex questions about their symptoms. With a validated observational tool for RLS diagnosis, the Behavioral Indicators Test-Restless Legs, we aim to diagnose RLS and determine the effect of gabapentin enacarbil (GEn) compared to placebo on nighttime agitation, sleep, antipsychotic medications, and the mechanism for these effects. We hypothesize that frequency of RLS behaviors will mediate the relationship between GEn and nighttime agitation. This study is an 8-week, double-blind, placebo-controlled, randomized pilot clinical trial, followed by an 8-week open-label trial, that is being conducted in long-term care settings and private homes. The results of this study may shift, personalize, and improve standards of care for treatment of nighttime agitation; reduce aggression and other nighttime agitation behaviors; and improve sleep. TARGETS: Persons with AD with nighttime agitation potentially caused by RLS. INTERVENTION DESCRIPTION: Diagnose RLS and determine the effect of GEn. MECHANISMS OF ACTION: The frequency of RLS behaviors will mediate the relationship between GEn and nighttime agitation. OUTCOMES: Determine the effect of GEn on nighttime agitation, sleep, and antipsychotic medications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03082755 (Date of registration March 6, 2017). [Research in Gerontological Nursing, 13(6), 280-288.].