© Springer-Verlag Wien 2015
Aleksandar Videnovic and Birgit Högl (eds.)Disorders of Sleep and Circadian Rhythms in Parkinson’s Disease10.1007/978-3-7091-1631-9_66. Insomnia in Parkinson’s Disease
(1)
Rush University Medical Center, Sleep Disorders Service and Reacher Center, 710 S Paulina Street, Chicago, IL 60612, USA
(2)
Department of Neurological Sciences, Rush University Medical Center, 1725 West Harrison Street, Suite 755, Chicago, IL 60612, USA
6.1 Introduction
6.2 Definition
6.4 Evaluation
6.4.1 Evaluation Tools
6.5.1 Other Sleep Disorders
6.6 Treatment
6.6.1 Behavioral Treatment
6.7 Conclusion
Abstract
Insomnia is the most common sleep disorder in Parkinson’s disease (PD). Sleep maintenance insomnia is the most common type of insomnia in this population. The pathophysiology of insomnia is complex and not fully understood. Contributing factors to insomnia in PD include complex medication regimens and comorbidities associated with the disease. A dedicated sleep interview that includes patients’ bed partners or care givers is a necessary diagnostic step in the management of insomnia. Treatment options include non-pharmacological and pharmacological approaches.
6.1 Introduction
Sleep complaints are highly prevalent in patients with Parkinson’s disease (PD). Up to 88 % of PD patients report nighttime sleep fragmentation and early morning awakenings, [1] which are associated with decreased overall total sleep time, increased wake periods in the middle of the night (“wake after sleep onset periods,” or WASO), poor daytime function, and excessive daytime sleepiness (EDS). Up to 60 % of PD patients specifically complain of insomnia [2], which objectively correlate with daytime fatigue and sleepiness [3], impaired attention and executive functioning [4], and caregiver burden [5, 6]. Subjectively, PD patients cite insomnia as a significant source of distress [7, 8]. Insomnia is frequently the cause of low quality of life for both the PD patient and their caregivers [6, 8]. Despite this, research investigating insomnia in PD has been relatively sparse, possibly due to the complex, multifactorial nature underlying the relationship between insomnia and PD.
This chapter is intended to provide a brief overview of insomnia, discuss the phenomenon of insomnia in PD, provide suggestions regarding evaluation of insomnia and its application in PD, and review potential treatment options for insomnia in PD.
6.2 Definition
The definition of insomnia has been a source of contention for several years. There are debates regarding how to differentiate the symptom from the disorder, whether specific time thresholds should be included (e.g., how long it takes to fall asleep, duration of WASO periods), and how to combine these sleep complaints with daytime, or “wake,” complaints (e.g., fatigue or sleepiness) [9]. Generally, there is consensus that the core symptoms of insomnia should involve at least one nighttime or sleep symptom (e.g., difficulty initiating or maintaining sleep, early morning awakenings, non-restorative sleep) and at least one daytime or wake symptom (e.g., fatigue, mood issues, cognitive dysfunction, social or occupational impairment, EDS) [9, 10].
Diagnostic criteria for insomnia are included within the following three different classification systems: the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-V) [11]; the International Classification of Diseases, 10th revision (ICD-10) [12]; and the International Classification of Sleep Disorders, 3rd edition (ICSD-3) [10]. For this discussion, the ICSD-3 criteria for chronic insomnia disorder will be used which include difficulty initiating or maintaining sleep, early morning awakening, and patients’ complaints related to poor nighttime sleep.
For PD patients, risk factors for insomnia include having PD itself (e.g., motor symptoms), treatment factors (e.g., medication side effects, wearing-off effects), psychosocial disturbances (e.g., depression, anxiety), and comorbid medical disorders. It is important to note that PD patients may have overlapping insomnia and other sleep disorders. Below is a brief summary of each of these diagnoses as it may pertain to PD.
Difficulty initiating or maintaining sleep may be considered a common symptom of an underlying existing medical condition. For PD patients, motor symptoms can be especially disruptive or disturbing at night [13]. For example, bradykinesia causes difficulty turning in bed, requiring frequent readjustment of pillows and blankets. Early morning dystonia is a common complaint, when dopamine levels are low or are not supplemented by medications, leading to severe contractures that disrupt sleep. Non-motor PD symptoms can also interfere with sleep, particularly autonomic dysfunction. Urinary and gastrointestinal dysfunction during sleep is known to significantly contribute to insomnia complaints [14–16]. When these PD-related symptoms lead to concern or distress to the point of causing loss of sleep or prolonged WASO, this insomnia diagnosis should be considered.
The bidirectional relationship between insomnia and mood disorders, specifically depression and anxiety, has been well documented. Insomnia may be a symptom of a variety of mental disorders, but patients also cite insomnia as a potential trigger or exacerbator of their mood or mental disorder. In PD, depression is highly prevalent [17, 18], possibly associated with dysfunction of dopaminergic transmission, a notion that is partially supported by improvement after dopamine agonist administration [19]. Additionally, movement issues can increase anxiety and depression symptoms, which can also affect sleep quality. Mood disorders in PD must be evaluated independently of motor symptoms, as depression can lead to maladaptive behaviors that can worsen insomnia [10, 20].
Medications used to help PD-related motor symptoms may alternately cause daytime sleepiness and nighttime hyperarousal [21]. Direct effects on the sleep and wake systems may depend on dose and timing of the medications. For example, levodopa 200 mg in the evening may improve subjective sleep quality [22], but continuous dopaminergic therapy has been shown to worsen sleep fragmentation [23]. Non-selective MAO-B-inhibitors have been reported to cause both daytime sleepiness and sleep disruption, possibly due to an amphetamine-like metabolite [24] that has not been reported with selective MAO-B-inhibitors [25].
Medications that may also help with non-motor symptoms can also exert deleterious effects on sleep and wake function. For example, antidepressants can have either an alerting or sedating effect, so correct timing of these medications is important. A thorough review of medications (including over-the-counter preparations), side effects, dosage, and timing of administration is recommended.
6.3 Pathophysiology and Sleep-Wake Systems
PD pathology involves lesions in the upper brainstem and lower midbrain [15], areas that are crucial in sleep and wake regulation. Alterations of brainstem cholinergic and noradrenergic neurons can result in altered REM sleep, while loss of serotonin is associated with reduced slow wave sleep. It is important to remember that PD pathology also affects wake systems [21]. As brainstem dopaminergic, cholinergic, and serotoninergic neurons, along with forebrain acetylcholine and histamine, are integral to the arousal system, PD-related neurodegeneration fundamentally alters the ability to sustain wakefulness. PD patients may also have relative losses of orexinergic neurons in the lateral hypothalamic region, which normally provides excitatory signals to these same arousal systems [26]. The overall result is an altered arousal threshold, leading to increased susceptibility to sleep (i.e., daytime napping), which can hinder the ability to initiate and consolidate nighttime sleep.
Early involvement of PD pathology within the brainstem regions [15] may explain the high frequency of insomnia complaints even in the mild stages of PD, suggesting that insomnia steadily worsens as PD progresses. On the contrary, insomnia in PD has been shown to fluctuate over time [27]. Similarly, various imaging techniques have failed to associate sleep disturbances with specific structural abnormalities in PD [28] suggesting that PD-related insomnia is not solely attributed to brainstem neurodegeneration.
6.4 Evaluation
As with any medical disorder, evaluation of insomnia should begin with a thorough history that includes frequency and duration of symptoms, exacerbating and relieving factors, average and range of bedtimes, perceived sleep latency, number of arousals, duration of WASO, average and range of wake times, and perceived quality of sleep. Discussion regarding behavioral habits during the 24-h day may include levels of activity during the day, daytime napping habits, use of non-sleep activities while in bed such as use of electronics, and environmental factors (e.g., temperature, noise, pets). Medical and psychiatric history should be considered in the context of the timing of symptoms, along with review of medications specifically including medications attempted for treatment of sleep and wake symptoms (including over-the-counter preparations) and a review of medications that can potentially influence sleep and wake rhythms (e.g., antidepressants, steroids, antihistamines, etc.) [29, 30].
Because of the complexity of insomnia in PD, evaluation and management of PD is necessarily multifaceted. In addition to a thorough history and examination, clinicians are encouraged to reevaluate both the timing and dose of PD pharmacotherapy, as this may help insomnia by either directly helping with nighttime sleep consolidation (e.g., by reducing nocturnal akinesia or dyskinesia that may interfere with sleep) or indirectly by reducing daytime sleepiness (i.e., increasing wake periods during the day, thereby helping with nighttime sleep latency and consolidation). Concomitantly, consultation for associated comorbid medical issues (e.g., urological issues) is recommended to reduce the potential interference of nighttime sleep consolidation. Consistent reevaluation of psychiatric and psychological symptoms is recommended to adequately address symptoms of depression, anxiety, hallucinations, and panic from interfering with sleep and wake function. Finally, consultation with a clinician who is experienced with the diagnosis and management of insomnia is often helpful.
6.4.1 Evaluation Tools
For PD, six scales have been deemed to meet criteria as per the movement disorders task force [31]: the Pittsburgh sleep quality index (PSQI), the Epworth sleepiness scale (ESS), the inappropriate sleep composite score (ISCS), the Stanford sleepiness scale (SSS), the Parkinson’s disease sleep scale (PDSS) [32], and the scales for outcomes in Parkinson’s disease (SCOPA-sleep) [33]. The first four scales are generic sleep tools, generally limited in their ability to evaluate PD-specific sleep symptoms, while the latter two scales have been developed to be specific to PD. The PDSS is a visual analogue scale that includes PD-related nocturnal symptoms including overall quality of nighttime sleep, sleep onset and maintenance insomnia, nocturnal restlessness, nocturnal psychosis, nocturia, nocturnal motor symptoms, sleep refreshment, and daytime dozing. A modified version, the PDSS-2, includes screening for sleep apnea, and is reported to have an excellent level of validity and reliability. The SCOPA-sleep is a short, two-part scale that assesses nighttime sleep and daytime sleepiness. Although this scale has been validated, it does not incorporate other PD-specific problems such as nocturnal hallucinations, motor symptoms, or nocturia. The PDSS and SCOPA-sleep scales have been developed specifically for PD patients, with incorporation of items to assess nocturnal sleep quality and impairment. However, while more applicable to sleep symptoms in PD, neither scale has been evaluated specifically for PD-related insomnia.
Available tools for insomnia assessment typically consist of sleep diary and actigraphy measures. Sleep diaries are subjective tools that help identify patterns of sleep [34]. Patients are typically asked to keep a prospective record of their bed times, WASO, wake times, and sleep quantity and quality over a course of a few weeks. Patients are usually instructed to record this information during the morning times, using recall of the previous night’s sleep to complete this information. Using these records, parameters such as time-in-bed along with subjective ratings of sleep and wake function can be estimated. Sleep diaries do not necessarily correlate with objective measures of sleep, but this data can help identify important factors related to the insomnia complaints. Further, sleep diaries can be used to assess treatment response [35, 36]. Actigraphy is an accelerometer device that monitors motion and calculates activity counts, providing objective information regarding sleep and wake patterns over several days or weeks. It is considered a useful evaluative tool for insomnia [37, 38], particularly in assessing whether certain patterns of sleep emerge or to evaluate the implementation of behavioral methods such as sleep restriction on existing patterns.
Although sleep studies (polysomnography, or PSG) are considered the gold-standard assessment for most nocturnal sleep disorders, PSG is not recommended for routine assessment of insomnia [39]. However, as comorbid sleep disorders are highly prevalent in PD patients, PSG is often utilized to evaluate potential sleep apnea, periodic limb movement disorder, and REM behavior disorder.
6.5 Differential Diagnoses
6.5.1 Other Sleep Disorders
While discussion regarding other nocturnal sleep disorders is out of the scope of this chapter, it is important to note that PD patients often have comorbid sleep disorders including sleep apnea, restless leg syndrome (RLS), periodic limb movement disorder, and REM behavior disorder that contribute to sleep fragmentation, poor sleep quality, and daytime dysfunction. Evaluation and treatment of these disorders may improve the insomnia complaint, in which case an independent diagnosis of insomnia is excluded. However, it is also possible that insomnia is persistent and separate from these other sleep disorders. Further, the existence of these sleep disorders may potentially exacerbate insomnia symptoms and interfere with treatment of insomnia [40]. For example, patients may be unable to adhere to relaxation techniques for insomnia (CBT-I) if RLS symptoms are present. The symptoms of these sleep disorders should be considered during the initial evaluation as well as during subsequent follow-up visits.
6.5.2 Circadian Rhythm Sleep Disorders
The circadian system is suspected to be affected in PD-related pathophysiology, substantiated by reports of advanced sleep-wake schedules (i.e., early bedtimes and early wake times) in PD patients. Though the suprachiasmatic nucleus of PD patients is likely not involved, aberrant clock genes [41] and abnormalities in circadian hormonal patterns [42, 43] are reported. Clinically, circadian involvement in PD is partially supported by the beneficial effect of administering bright light in PD patients [44]. However, it is yet unclear whether the clinical observation of circadian misalignment in PD is mediated directly by alterations in the circadian system or via other indirect pathways (e.g., age, depression). Evaluation of insomnia should include a review of preferred versus habitual sleep and wake times to consider circadian rhythm disorders into the differential diagnosis.
6.6 Treatment
6.6.1 Behavioral Treatment
For movement issues, the comfort of the PD patient during the night can be improved by simple measures. For example, PD patients may find relief by using sheets that do not slip, wearing silk pajamas without buttons, and placing levodopa tablets and a bottle of water on the bedside table. In advanced stages of the disease, the patient’s spouse should be encouraged to sleep in a different bed or room as needed, as inadequate rest for the caregiver can make the patient’s sleep disturbance intolerable and lead to early institutionalization.
Enhancing both daytime activities and assisting with calming nighttime activities can provide insomnia relief. Increased activity during the day helps to increase “sleep pressure” so that sleep latency at bedtime is reduced. Nighttime measures may include stimulus control, proper sleep hygiene, and sleep restriction. Stimulus control is a set of instructions to reinforce the association between sleep and the bed/bedroom [45]. Examples include going to bed only when feeling sleepy, avoiding activities other than sleep in the bed/bedroom (e.g., no reading or watching TV), getting out of bed if sleep is not achieved in an acceptable amount of time, keeping a routine sleep-wake schedule (e.g., same wake time regardless of the amount of sleep perceived the night before), and avoidance of daytime napping. Proper sleep hygiene habits are also advised. For example, use of evening caffeine may cause evening alertness as well as worsen PD-related urinary processes. Restriction of daytime napping is also crucial in allowing for improved nighttime sleep onset latency and nighttime sleep consolidation. Patients may also be instructed to adjust environmental influences (e.g., light, noise, temperature) that may promote or interfere with sleep [46]. Sleep restriction involves limiting the amount of time-in-bed so as to reflect, as close as possible, the actual sleep time. Sleep efficiency, which is the amount of time sleeping divided by the amount of time in bed, is one outcome that helps guide treatment efficacy. Once acceptable sleep efficiency is achieved, the time-in-bed is gradually increased. For the PD patient, the caveat in implementing these particular behavioral techniques is potential worsening of daytime sleepiness, so caution with risky behaviors during the day such as driving (especially due to potential dopaminergic influence) need to be considered.
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