ORIGINAL STUDY Sleep Quality in Parkinson Disease: An Examination of Clinical Variables Karina Stavitsky, MA and Alice Cronin-Golomb, PhD disturbances may also be secondary to motor discomfort3 Abstract: The etiology of sleep problems in Parkinson disease or to nonmotor features of the disease.4 Dopaminergic (PD) is not well understood, as they may arise from the medication may increase sleep fragmentation and reduce pathology of the disease or from other disease-related factors sleep efficiency,5 or may cause daytime sleepiness.3,6 such as motor dysfunction, dopaminergic medication, and mood Anxiety and depression, common in PD, can also cause disturbances. The aim of this study was to investigate factors problems with sleep onset and maintenance and daytime associated with sleep, including disease-related variables such as alertness.7,8 motor symptom severity, dose of medication, and mood and PD is heterogeneous in its presentation. Studies disease subtypes. Thirty-five nondemented patients with PD were have focused on disease subtypes including PD into left included. Sleep was measured using 24-hour wrist actigraphy (LPD) and right (RPD) side of motor symptom onset, over a 7-day period, during which time participants kept a sleep type of initial motor symptom, and sex. Differences in diary. Subjective sleep and arousal questionnaires included the cognitive performance, disease progression, and nonmo- PD Sleep Scale and Epworth Sleepiness Scale. Motor symptom tor features have been reported in subtypes of the disease. severity and dopaminergic medication were significantly related In regard to side of onset, LPD and RPD show distinct to measures of sleep quality. Sex differences in sleep quality were profiles of cognitive functioning,9,10 sleep disturbances,11 found, with men having worse sleep quality and more excessive and visual hallucinations.11,12 Findings of sleep differ- daytime sleepiness than women. We also found that actigraphy ences in LPD and RPD, however, have been limited to may serve as a useful tool for identifying individuals with use of sleep questionnaires. In regard to type of initial possible rapid eye movement behavior disorder, a sleep disorder motor symptom, individuals who present with tremor do- that has important implications in early detection of PD. minant (TD) versus nontremor dominant (NTD) symp- Key Words: Parkinson, sleep, actigraphy, sex toms express distinct clinical and cognitive profiles. Patients who present with primarily gait and balance (Cogn Behav Neurol 2011;24:43–49) disturbance tend to have more rapid progression of disease, including more severe cognitive deficits and a faster onset of dementia than patients with TD.13 No studies have leep problems in Parkinson disease (PD) are among examined sleep quality with respect to TD and NTD. Sthe most prominent nonmotor symptoms of the Sex differences have been found in both motor and disease, impacting the quality of life of patients and nonmotor aspects of PD.14 In the general population, caregivers.1 Patients with PD experience a variety of sleep- women report more frequent insomnia and restless legs related problems, including rapid eye movement (REM) syndrome, whereas REM behavior sleep disorder, char- Behavior Disorder (RBD), sleep fragmentation and acterized by loss of normal muscle atonia and acting-out reduced sleep efficiency, and excessive daytime sleepiness.1 of dreams, is more common in men.15 The examination of Some aspects of sleep disruption arise from the sleep quality with respect to sex has not been investigated underlying pathology of the disease.2 The pathogenesis of in patients with PD. PD, which begins in the brainstem and results in neuronal The aim of this study was to examine the association loss in the cholinergic, dopaminergic, and serotonergic of sleep and varying clinical presentations and symp- systems, is likely to affect the reticular formation that toms in patients with PD, using an objective measure is implicated in sleep and wake regulation.2 Sleep [actigraphy (ACT)] and subjective assessments (sleep questionnaires). This study focuses on the correlates of sleep disturbance in those with PD rather than the question Received for publication March 25, 2010; accepted March 14, 2011. of whether such disturbance exists, as this has already been From the Department of Psychology, Boston University, Boston, MA. demonstrated in numerous previous studies.1 Supported by a Ruth L. Kirschstein National Research Service Award (1F31 NS061555-01) and a Clara Mayo Foundation fellowship from the Department of Psychology, Boston University, to KS, and by NINDS grant R01 NS050446-01A2 to A.C-G. METHODS Reprints: Alice Cronin-Golomb, PhD, Department of Psychology, Boston University, 648 Beacon Street, 2nd floor, Boston, MA Participants 02215 (e-mail: [email protected]). Thirty-five patients with PD (22 men, 13 women) Copyright r 2011 by Lippincott Williams & Wilkins were recruited from the outpatient Movement Disorders Cogn Behav Neurol Volume 24, Number 2, June 2011 www.cogbehavneurol.com | 43 Stavitsky and Cronin-Golomb Cogn Behav Neurol Volume 24, Number 2, June 2011 Clinic at the Boston Medical Center (Table 1). The study sleep software version 5.3 (Mini Mitter). Results were was approved by the Boston University Institutional averaged across the 7 days of monitoring. The measures Review Board and all participants provided informed were sleep latency (first 10-min period with <2 epochs of consent. On the modified Mini-Mental State Examination activity), sleep time [sum of time (in minutes) of epochs (mMMSE),16 a cut-off score of 25 was used, as this form not exceeding the sensitivity threshold], sleep efficiency of the MMSE is particularly sensitive to specific cognitive (sleep time divided by the time in bed multiplied by 100), deficits found in PD without dementia (scores converted wake after sleep onset (total time awake after the first from the 57-point scale). Individuals with a history of sleep onset period), and movement and fragmentation substance abuse, head injury, or neurologic disorders be- index (number of 1-min periods of immobility relative to sides PD were excluded. None of the patients met criteria the total number of immobility phases). for dementia with Lewy bodies as per McKeith et al.17 Medication information was obtained for all parti- Subjective Measures cipants. Levodopa equivalent dosages (LED) were calcu- Sleep complaints were assessed using the Parkinson lated based on previous reports with LED: (regular Disease Sleep Scale (PDSS),20 which has been used to levodopa dose  1)+(levodopa controlled-release dose identify disturbances such as sleep maintenance, insom-  0.75)+(pramipexole dose  67.0)+(ropinirole dose nia, and excessive daytime sleepiness. The scale consists of  16.67)+(rotigotine  16.67)+(pergolide dose and 15 common symptoms. A score of 10 indicates worse cabergoline dose  67.0)+(bromocriptine dose  10)+ symptoms and 0 indicates no symptoms. We examined [(regular levodopa dose+levodopa controlled-release the 15 items as 9 factors comprising composite scores of dose  0.75)  0.25] (if taking tolcapone or entaca- the individual items, as described elsewhere.20 The factors pone)].18 were overall quality of sleep, sleep onset and maintena- Motor symptom severity was quantified using the nce, insomnia, nocturnal restlessness, nocturnal halluci- Unified Parkinson Disease Rating Scale (UPDRS) and nations, distressing/vivid dreams, nocturia, nocturnal Hoehn and Yahr stage. Information on the side and type motor symptoms (sensory complaints, early morning of motor symptom at onset was obtained through patient dystonia, and cramps during the night), sleep refresh- report, confirmed when possible by neurologist review. ment, and daytime dozing. We also used the PD Sleep Mood was assessed using the Beck Depression Inventory Questionnaire from our laboratory, which captures some (BDI-2) and Beck Anxiety Inventory (BAI). All patients symptoms not assessed by the PDSS, including questions received the PD Quality of Life questionnaire-39).19 assessing for RBD. Owing to the relationship between sleep disorders Sleep Measures and subjective daytime sleepiness, we administered the 21 Objective Measure Epworth Sleepiness Scale (ESS). The score range is 0 to To measure activity during the sleep/wake cycle, the 24, with a score of 10 or more indicating excessive day- time sleepiness. The questionnaire is commonly used in participants wore wrist actigraphs (Actiwatch AW-64; 22,23 Mini Mitter, Sunriver, OR) continuously over a 1-week PD to assess the likelihood of dozing off in a variety period on each wrist. Data from the nondominant wrist of daily situations. only was used for this study, as per convention. The Statistical Analyses actigraphs were set to a medium sensitivity with 40 counts Patients were recruited without regard to sex or assessed as “wake” and an epoch length of 30 seconds. motor symptom subtype. Independent sample t tests were The Actiwatch data were downloaded to the Actiware used to compare demographic and clinical characte- ristics of the sex and motor symptom subgroups. Pearson TABLE 1. Demographic and Clinical Characteristics of PD correlations reflected associations between sleep and Sample clinical variables such as mood and disease severity (ie, (n = 35) UPDRS total, disease stage and duration, and LED). Alpha of 0.01 was used for all correlations and analyses Age (y) 66.2 (7.9) Education (y) 16.8 (2.4) by subgroups. As there were significant correlations Men:women 22:13 among all 5 ACT variables, Bonferroni adjustment was BDI total 8.31 (4.7) used to set a to 0.01 (0.05/5). Of the 9 PDSS variables, BAI total 8.26 (4.9) only some of them were correlated (number de- UPDRS total 25.1 (9.4) Disease stage* 2 (2) pending on variable), and accordingly an a of 0.01 was Disease duration (y) 8.84 (5.1) used here as well. LED 604.3 (283.5) Dopamine agonist (%) 77.1 Sleep medication (%) 14.7 RESULTS Means (SD) are reported unless otherwise indicated.