Introduction

Parkinson’s disease (PD) stands as the second most common neurodegenerative disorder globally, impacting more than 6 million individuals in 2016 [1]. The prevalence of PD increases with age and varies based on geographic location and gender [2]. From 1990 to 2019, the incidence of PD surged by 159.73% [3]. In China, the regional incidence of PD was approximately 13.24 per 100,000 population in 1990, rising to 15.27 per 100,000 population in 2019 [4]. Similarly, in the United States, the incidence of PD in people aged 65 and older ranges from 108 to 212 per 100,000 person-years [5].

The pathophysiology of PD remains not fully understood. While inclusion bodies, such as Lewy bodies, indicate lesions and potential onset, their presence is not confined to the medulla oblongata and olfactory bulb during the prodromal stage. Emerging evidence suggests that PD may involve both central and peripheral nervous systems early in the disease course, particularly in patients with sleep dysfunction and autonomic disturbances [6]. Subsequently, as the disease progresses, the substantia nigra and other midbrain and forebrain nuclei become affected [7]. While not all causes of PD are unveiled, common risks, including genetic factors [8], environmental effects [9], lifestyle reasons, and comorbidities [10], have been identified. Characterized by the loss of dopaminergic neurons in the substantia nigra, PD manifests as motor symptoms, including bradykinesia, tremor, and rigidity. The pathology of PD also involves the accumulation and spread of alpha-synuclein (α-Syn) beyond the substantia nigra to other brain areas, contributing to various non-motor symptoms [11]. These non-motor symptoms, such as anxiety, sleep disorders, and cognitive impairment like dementia, notably affect patients’ quality of life (QoL) [12]. Among these non-motor symptoms, sleep disorders are particularly significant.

Sleep disorders are common among PD subjects and can significantly impact their sleep patterns and quality [13]. In China, it is estimated that 48–89% of PD patients experience sleep disorders [14]. Globally, sleep disorders affect a large percentage of the general PD population, ranging from 64 to 90% [15, 16]. The most frequently reported sleep complaints by PD patients include insomnia (27–80% [17]), excessive daytime sleepiness (EDS, 20–60% [18]), restless legs syndrome (RLS, 4–15% [19]), and REM sleep behavior disorder (RBD, 33–46% [20]) [21]. These sleep disorders drastically contribute to the complexity of sleep-related difficulties experienced by PD patients.

However, when focusing specifically on PD patients who already experience some form of sleep disturbance, the prevalence rate of insomnia reaches 36.9% [17]. According to the International Classification of Sleep Disorders-Third Edition (ICSD-3), insomnia is defined as a sleep disorder characterized by difficulties initiating or maintaining sleep or by nonrestorative sleep, occurring at least three nights per week, resulting in adverse daytime impairment [22]. Within PD, the heterogeneity of insomnia results from various factors that differ among patients. These factors include the progression of the disease and neurodegeneration affecting sleep-regulating brain structures, medication side effects, comorbid neuropsychiatric conditions such as depression or anxiety, frequent nighttime urination, and other sleep disorders like REM sleep behavior disorder, or motor symptoms like restless legs syndrome [23, 24]. Furthermore, patients commonly report more difficulty maintaining sleep than initiating it, largely due to neurodegeneration impacting circadian regulatory mechanisms [25,26,27].

Chronic insomnia can worsen sleep quality and contribute to both non-motor [28] and motor symptoms [29] in PD patients. A recent cross-sectional study has indicated that PD patients with a higher level of insomnia demonstrate higher degrees of depression and anxiety, which negatively impact their health-related quality of life (HRQoL) compared to those without insomnia or with milder insomnia [30]. Insomnia and sleep deprivation are commonly observed in the early stages of PD, and as the disease progresses, insomnia symptoms tend to worsen, posing challenges to HRQoL, motor abilities, cognitive impairments, and emotional well-being [31]. Conversely, insomnia, when combined with other motor symptoms, can further disrupt sleep and lead to worse sleep conditions [32].

Although insomnia has been a frustrating symptom for PD patients, it has received limited attention compared to the more extreme motor symptoms that significantly impact patients’ health. However, evidence suggests that a decline in sleep quality is associated with an increased risk of developing PD [33]. Some theories propose that early PD pathology disrupts regular circadian rhythms, while others suggest that sleep disturbance may contribute to the development of PD [34]. Additionally, a possible feedback loop has been hypothesized, indicating that sleep disturbance, triggered by PD’s pathophysiology, can further worsen the progression of the disease [34].

The purpose of this review is to primarily focus on insomnia in PD and examine its prevalence worldwide. It covers the pathophysiology and diagnosis of insomnia in PD, risk factors, treatment and management strategies, and the impact on public health. Furthermore, the review identifies current research gaps and suggests future directions to ensure a comprehensive analysis.

Epidemiology

The differences in prevalence observed across various studies can result from many factors, including genetic backgrounds, geographical locations, and environmental influences. Additionally, variations in the target populations, research methodologies, and diagnostic criteria can also contribute to the variations in prevalence used in these studies can also contribute to the discrepancies in prevalence rates. The global prevalence of insomnia in the general population varies from 5 to 35% worldwide [35], which increases to 37 to 80% when limited to the PD population [17, 36, 37]. Among subtypes of insomnia, more than 80% of patients complain of difficulty in sleep fragmentation, 18% in initiating sleep, and 40% in early awakenings [38]. However, the actual prevalence can be higher because not all PD patients with insomnia receive appropriate diagnoses.

On a large scale, there are no geographical discrepancies in the prevalence of insomnia in PD. A longitudinal study in the Netherlands revealed that 27% of the total 421 PD patients had insomnia at the baseline; in comparison, 33% of PD patients developed insomnia at some point during 5 years of follow-up [37]. In several respective studies conducted in Norway, 50% of the total 231 PD patients initially presented with insomnia [23, 39], and this prevalence increased to 63% when narrowed down to PD patients who also had EDS [40, 41]. A cohort study in Taiwan reported a prevalence of insomnia in more than 45% of the 91,273 PD patients without sleep apnea [42]. The first sub-Saharan Africa study showed a prevalence of over 30% among 155 participants [43], comparable to that in India [44]. Another study in Malaysia suggested a prevalence of 31.8% among 44 patients [45]. A study in the UK demonstrated that 46.2% of participants reported poor sleep quality using the Pittsburgh Sleep Quality Index (PSQI) [46, 47]. A study in the United States reported a 31% baseline prevalence of insomnia in 182 patients upon medication initiation [48]. The prevalence of insomnia in PD is demonstrated in Fig. 1.

Fig. 1
figure 1

Prevalence of insomnia in PD by country. No regional differences are shown according to the global research. *Data for the UK were obtained from participants who reported poor sleep quality using PSQI

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Moreover, a comparison study conducted both in Japan and the UK also indicated no racial contributions to the extent of sleep disability. However, some disparities were shown in sleep issues. Patients with PD in Japan reported more difficulties with sleep initiation and maintenance than the control group; in contrast, patients in the UK only reported problems with sleep maintenance [49].

Clinical Manifestation, Pathophysiology, and Diagnosis

Clinical Features and Subtypes of Insomnia in PD

Insomnia is characterized by difficulties initiating sleep, maintaining sleep, and waking early. According to a recent study, a significant number of PD patients with insomnia reported trouble falling asleep at the beginning of the night (18%) and early morning awakening at the end of sleep (40%). They also experienced fragmented sleep, frequent awakenings throughout the night, and difficulty sustaining sleep (81%) [17, 50]. Motor symptoms, such as nocturnal motor disturbances, including tremors, rigidity, and akinesia, contribute to sleep disruption in PD patients [51]. Additionally, non-motor symptoms, such as fatigue, depressive mood, anxiety, and autonomic issues, are closely and independently associated with insomnia in PD [52]. Autonomic dysfunction, including nocturia and gastrointestinal symptoms [52], along with internal circadian dysrhythmia [44], are also associated with insomnia in PD.

Gender has been identified as a contributing factor to the disparities in the prevalence of insomnia in PD, with a higher frequency observed among females than males [23, 37, 45]. This may be partially attributed to a study conducted in Taiwan, which found that women had a twofold chance of developing depression and anxiety [53], as mood disorders are linked to insomnia [54]. Additionally, Norlinah et al. reported a decline in sleep quality as depression progressed, age advanced, or the disease course extended [45, 52]. Furthermore, Gjerstad et al. noted that the prevalence of insomnia could reach up to 54 to 60% in more advanced PD patients [23]. Although the relationship between age and sleep quality is well-established and generally accepted, some studies within the context of PD have reported no association between age or disease duration and sleep quality [48, 55, 56]. Depression is commonly associated with insomnia and has a bidirectional relationship [34, 52, 57, 58]. Patients with depression often experience delayed sleep onset, disruption of sleep, reduced slow-wave sleep, and altered REM sleep. However, the role of depressive mood in PD patients is often underestimated, possibly due to confusion of symptoms with other conditions.

Medication contributes to insomnia or EDS in PD patients, as dopaminergic drugs can hold side effects such as EDS or sleep attacks. A higher medication usage or the presence of medication is associated with EDS and insomnia [37, 52]. Additionally, the quality of diet may be related to the progression of insomnia in PD. Several studies have examined different populations and have found that high-quality diets are associated with improved sleep quality among prodromal PD patients [59,60,61].

Extra attention should be emphasized to patients’ mood and usage of medication, as these are common causes or results of insomnia in PD patients, which are often neglected or receive little attention. Insomnia in PD is a complex issue that involves a sophisticated interrelation with pathophysiological changes, comorbidities, and risk factors.

Neurobiological Mechanisms of Insomnia in PD

Neurodegenerative changes occur through the course of many neurodegenerative diseases [62]. Some common factors contributing to the death of neurons include abnormal protein dynamics and misfolding, oxidative stress, mitochondrial dysfunctions and DNA damage, and neuroinflammatory diseases [63]. PD is characterized by the accumulation of microglia cells and astrocytes, as well as the buildup of alpha-synuclein (α-Syn) in Lewy bodies [64, 65]. These depositions initiate neuron inflammation and cell death [62]. In addition to lesions occurring in the Substantia nigra, nerve cell loss extends to sleep-related subcortical nuclei, including locus coereleus, pedunculopontine nucleus, raphe nuclei, the suprachiasmatic nucleus (SCN), and hypothalamus [66]. Neurodegeneration in these nuclei leads to non-motor PD symptoms that are not effectively treated with dopaminergic treatments, although the exact pathophysiological reasons remain unclear [67]. While the traditional consensus is that neurodegenerative diseases trigger sleep disorders, more studies have proposed and discovered a reciprocal relationship between sleep disorders and neurodegenerative diseases [34, 57]. The pathophysiology of insomnia in PD can be primarily attributed to neurodegenerative changes, circadian rhythms, and basal ganglia beta oscillations.

On the other hand, emerging studies also suggest that insomnia may contribute to neurodegeneration through mechanisms such as impaired glymphatic system and disrupted N3 sleep. The glymphatic system, responsible for cleaning the metabolic waste out of the brain, is most active during N3 sleep [68]. Impaired glymphatic function, often associated with insufficient N3 sleep, can lead to the accumulation of neurotoxic substances such as amyloid-beta and α-Syn, potentially accelerating neurodegenerative processes in PD [69]. Additionally, studies have shown that glymphatic system dysfunction is correlated with cognitive decline [70], and reduced N3 sleep is associated with increased neurodegeneration in PD patients [71]. These findings highlight the importance of the glymphatic system and disrupted N3 sleep in managing insomnia in PD. Further research is needed to explore these mechanisms and their impact on the progression of neurodegeneration in PD.

Neurodegenerative Changes

The regulation of the sleep–wake mechanisms involves multiple brain structures and neurotransmitter systems. Key brain regions include the brainstem, hypothalamus, and subcortical/limbic regions [72]. Within the brainstem, the locus coeruleus and the raphe nuclei play a role in regulating REM and non-REM sleep. Noradrenergic neurons in the locus coeruleus and serotoninergic neurons in the raphe nuclei, known as REM-off cells, interact with cholinergic REM-on cells in the nucleus reticularis pontis oralis to control the transitions between different sleep stages [73,74,75,76]. The hypothalamus, particularly the anterior and posterior regions, is essential for sleep–wake regulation, with the anterior hypothalamus promoting sleep and the posterior hypothalamus promoting wakefulness. The amygdala and thalamus, part of the subcortical/limbic regions, also contribute to sleep regulation through their connections with other sleep-regulating areas.

Neurodegenerative changes in PD can impact various brain regions involved in sleep regulation, leading to sleep disorders. A retrospective study has categorized the pathological changes in the brain into three main pathways: alternations in the brainstem, the hypothalamus, and the subcortical/limbic regions [72]. These changes contribute to the pathophysiology of sleep disorders associated with PD. Additionally, specific brainstem regions, such as the locus coeruleus and raphe nuclei, are involved in regulating the sleep–wake cycle and arousal and have shown signs of lesions before the onset of motor symptoms in PD patients [77]. Affected regions are demonstrated in Fig. 2.

Fig. 2
figure 2

Affected areas of neurodegenerative changes due to α-Syn accumulation. (a) Region #1 brainstem: The accumulation of α-Syn has been observed in various regions of the brainstem, including the midbrain, pons, raphe nuclei, locus coeruleus, and nucleus reticularis pontis oralis. The locus coeruleus and nucleus reticularis pontis oralis house REM-off and REM-on cells, respectively. Their involvement is associated with combined effects on circadian rhythms and sleep regulation. (b) Region #2 hypothalamus: In the hypothalamus, α-Syn predominantly accumulates in the paraventricular nucleus, posterior hypothalamic nucleus, and para-mammillary nuclei. (c) Region #3 amygdala and limbic system: Within the amygdala and the limbic system, α-Syn accumulation is concentrated in the hippocampus and thalamus

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Firstly, an increase in α-Syn accumulation is observed in the brainstem among PD patients experiencing sleep problems, specifically within the locus coeruleus and raphe nuclei [72]. These nuclei are essential structures in regulating REM and non-REM sleep circuits. The degeneration of these cells likely contributes to sleep disturbances in PD, leading to a deterioration in sleep quality [72,73,74]. Additionally, the dorsal raphe nuclei in the midbrain and pons have been found to participate in sleep control by sending serotonergic signals to the cerebral cortex[75]. The anatomical link between PD and sleep disturbances, particularly RBD, suggests its origin in the lower brainstem, including the locus coeruleus, as Lewy bodies, Lewy neurites, and α-Syn accumulation have been detected in brainstem nuclei in RBD patients.

Another site of α-Syn pathology is the hypothalamus, primarily in the para-mammillary nuclei and the posterior hypothalamus, which also influences insomnia in PD [72]. The involvement of the posterior hypothalamus is associated with somnolence, while changes in the anterior hypothalamus cause sleeplessness [78]. This result aligns with the findings from Kalaitzakis et al. [72], which indicates the α-Syn pathology in para-mammillary nuclei and the posterior hypothalamus among PD patients with insomnia.

Lastly, the amygdala and thalamus, located in subcortical/limbic regions, are identified as essential factors contributing to PD sleep disorders [72]. The amygdala, known for its role in emotional processing [79, 80], has also been associated with sleep regulation [81,82,83]. It forms connections with the hypothalamus, basal forebrain, and brainstem, indicating its role in sleep control. The thalamus, an essential sleep regulator, coordinates the wake-sleep rhythm [81, 84]. A recent study has proposed that the paraventricular thalamus (PVT) is vital for regulating the sleep–wake circle [85]. Mechanistically, the connections between the PVT and the nucleus accumbens, as well as the links from hypocretin neurons in the lateral hypothalamus to PVT glutamatergic neurons, are the primary pathways of controlling wakefulness. High activity of glutamatergic neurons in the PVT during wakefulness and the suppression of neuron activity during sleepiness have been observed. Lesions in the PVT results in a decrease in wakefulness during the dark phase and a reduction in non-REM sleep episodes and micro-arousals, suggesting that neurodegenerative changes in these regions are associated with PD progression.

Circadian Rhythms

Emerging evidence suggests a possible causal connection between processes associated with PD and circadian rhythm disturbances [86]. Circadian rhythms, influenced by external signals like sunlight and internal signals like temperature [87,88,89], may trigger EDS or/and insomnia if the endogenous circadian timing system and external 24-h environment disrupt the coordination of these rhythms [90]. However, at an early stage of the disease, external factors are often overshadowed by lifestyle behaviors or other social settings [91]. A regular sleep–wake cycle contributes to a stable circadian rhythm amplitude [92]. Nevertheless, PD patients experience a suppressed amplitude of circadian rhythm, which is also a prodromal characteristic of PD [93]. A framework that demonstrates the neurological mechanisms of circadian rhythms underpinning insomnia in PD is shown in Fig. 3.

Fig. 3
figure 3

Neurological mechanisms of circadian rhythms in insomnia in PD. Patients with PD are associated with declined retina function, and light signals play a crucial role in regulating the SCN. The accumulation of α-Syn in the SCN, compounded by disrupted light signaling, impairs the functioning of core clock genes. Consequently, disturbances in circadian rhythms persist due to aberrant neural and hormonal signals, including altered melatonin secretion. The neuroinflammatory response, contributing to neural cell loss, exacerbates motor and cognitive impairment, thereby worsening PD progression and the severity of insomnia. On the other hand, PD has a direct impact on dopaminergic neurons, which regulate clock genes through transcriptional interference. The relationship between dysfunctional clock genes and dopaminergic neuron activity is bidirectional, contributing to the pathophysiology of insomnia in PD

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The SCN, located within the hypothalamus, is the primary regulator of circadian rhythms. Mechanistically, the SCN receives light information from the retina, coordinates the information from the surrounding systems, and adjusts internal clock rhythms accordingly [94]. The activation of SCN is linked to the regulation mechanisms of mood, sleep, and circadian rhythm [95]. The degradation of SCN activity is considered the key reason for the reduced melatonin secretion among elderly PD patients [96]. This is supported by a study that found lower levels of melatonin and higher levels of basal hypercortisolemia in PD patients compared to the elderly control group [92].

Moreover, the accumulation of α-Syn has been found to decrease the firing rate of the SCN, impairing the ability of the body to relay neural and hormonal signals from the central clock [97]. The accumulation of α-Syn in brain regions that regulate sleep physiology has been linked to sleep and circadian rhythm disturbances in PD patients [72]. On the other hand, potential damage to the SCN can contribute to the dysregulation of clock genes [92]. Emerging evidence suggests that the amplitude of the circadian system is weakened in patients with PD [98]. PD also results in decreased exposure to environmental light and impaired retinal function, collectively compromising the transmission of crucial signals to the SCN [99]. Specifically, PD patients exhibit reduced density of retinal ganglion cells and impaired pupillary light reflex compared to healthy individuals. These retinal changes compromise the effectiveness of light signals essential for maintaining circadian rhythms, exacerbating the disruptions observed in PD [100].

Furthermore, the degeneration of SCN activity has also been implicated in circadian disturbance [101]. The degeneration of dopaminergic neurons in PD can impact the SCN, leading to dysregulation of circadian rhythms, as supported by several studies [92, 102, 103]. The dopaminergic nigrostriatal pathway has been shown to regulate sleep patterns, particularly the bidirectional functions between dopamine and the circadian rhythm system [104]. Circadian genes regulate dopamine synthesis and dopaminergic activity through transcriptional interference [105]. In this regard, dopamine is considered to mediate essential Clock genes on a receptor-dependent basis [106]. It is established that both dopaminergic action and metabolism exhibit diurnal variations, with rhythmic patterns observed in the expression of dopamine receptors and tyrosine hydroxylase (TH), an enzyme integral to dopamine synthesis [107]. However, the precise influence of circadian disruption on the dopaminergic system remains uncertain.

Evidence suggests that an interruption in the circadian rhythm can exacerbate the motor and cognitive impairments associated with MPTP [108]. This exacerbation appears to be due to an increased neuroinflammatory response and enhanced neuronal cell loss. Specifically, subjects who experienced circadian disturbance before MPTP exposure displayed a markedly reduced number of TH-positive neurons, implying an increased susceptibility to MPTP toxicity and, consequently, more extensive dopaminergic neuronal loss in the affected brain regions.

These findings suggest that circadian disruption may contribute to the development and progression of various pathological features characteristic of PD. In this capacity, circadian interruption may act as an environmental risk factor contributing to the onset of PD. However, sleep plays a role in clearing accumulation products generated by neural activity during wakefulness [109], and circadian disruption may adversely affect and contribute to PD-related pathophysiology [110]. Further investigation into the relationship between sleep and circadian rhythm is needed to determine the impact of rhythm disputation [111].

Basal Ganglia Beta Oscillations

Basal ganglia beta oscillations refer to a specific pattern of brain wave activity that can be observed in the brain and are particularly prominent in the basal ganglia and motor cortex. In healthy individuals, beta oscillations engage in motor control and the regulation of voluntary movements. However, in PD, abnormal beta oscillations in the basal ganglia have been associated with motor symptoms and may also impact sleep and other functions [112].

A recent study using a nonhuman primate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD found a molecular pathway that contributes to insomnia in PD [113]. MPTP intoxication resulted in severe insomnia, characterized by delayed sleep onset, sleep fragmentation, and increased wakefulness. Non-REM sleep beta oscillations synchronized across the basal ganglia and cerebral cortex were observed during the onset of insomnia. Increased beta oscillations during non-REM sleep were strongly correlated with these sleep disturbances experienced in PD.

Also, human studies have provided support for these findings by demonstrating that beta activity in the basal ganglia is elevated during both non-REM and REM sleep stages in PD patients compared to those with dystonia [114]. Specifically, elevated beta activity during the N2 stage of NREM sleep has been associated with poorer sleep quality in PD. The severity of insomnia in PD patients is closely linked to the progression of the disease and can be treated by reducing pathological basal ganglia beta oscillations.

Comorbidities and Risk Factors for Insomnia in PD

For PD patients with insomnia, there is a complex interplay with comorbidities, including the persistence of motor symptoms and mental conditions, that can mutually contribute to each other, thereby threatening the QoL of this population [29, 34, 52, 57]. Furthermore, other risk factors include the influences of medical therapies [48, 52, 115, 116] and diets [59,60,61, 117,118,119].

Persistence of Motor Symptoms

Motor symptoms in PD patients also contribute to the deterioration of sleep quality, leading to sleep disturbances and complaints. Some studies have pointed out that motor symptoms such as rigidity, nocturnal hypokinesia, tremors, and impaired bed mobility can cause sleep maintenance problems, thereby worsening insomnia [120]. Sleep fragmentation can also occur due to conditions such as sleep apnea, periodic limb movement disorder (PLMD), and RLS, which involve abnormal muscular activities that disrupt sleep efficiency and REM sleep [121]. Additionally, the onset of RBD, characterized by the loss of control of REM sleep–related muscles and abnormal motor activities, can lead to intense dream-triggered behaviors that pose risks to both the patient and their bed partners [72]. Higher fluctuations of motor symptoms have been associated with increased severity of insomnia [37]. As a result, patients may experience a higher possibility of EDS, which can further hinder their ability to perform daily tasks, maintain independence, and negatively impact daytime concentration and cognitive functions [21, 53]. Furthermore, emerging studies have revealed that sleep disorders, including insomnia, may be prodromal characteristics of PD [122, 123]. This implies that sleep disturbances, including insomnia, could potentially serve as early indicators of PD development.

Psychological Conditions

Some studies have revealed the links between PD patients with insomnia and their moods. Depression is a common manifestation of PD and may contribute to sleep disturbance, as insomnia is considered an essential manifestation of depression [52]. Recent research has shown that up to 40% of PD patients have psychological conditions, highlighting the importance of identifying potential changes in mental status to prevent worsening sleep patterns [32]. A study has claimed a close link between depression and insomnia, with more than half of PD patients diagnosed with moderate depression also experiencing insomnia [124].

The prevalence of insomnia, depression, and anxiety increases with the progression of PD [125]. Patients with depression often reported more frequent and severe insomnia symptoms, indicating an earlier progression of depression compared to insomnia among PD patients [37, 126]. Additionally, a decline in sleep quality has been associated with an increased likelihood of developing PD [37]. Chronic insomnia can have a psychological impact, exacerbating mood-related symptoms and accelerating mood disorders [53, 127], leading to physiological and emotional alternations that promote the development of anxiety. Neurodegeneration in the brainstem is suspected to trigger the instability of RBD [128]. Depression and anxiety are also associated with enhanced sleep problems [23, 54]. Researchers have found that anxious or depressive moods can interfere with sleep quality in PD patients, further contributing to the progression of insomnia [58].

Medical Therapies

A study unveiled that insomnia is associated with depressive symptoms and the use of dopamine agonists rather than the duration of PD [23]. Medications used to treat PD, such as antidepressants, anticholinergics, and stimulants, can also contribute to sleep disturbance [51, 52]. Depressed mood in PD can be linked to dopaminergic dysfunction, as dopamine agonist medication, which stimulates dopamine activity, can alleviate depression-triggered symptoms [52, 115]. Additionally, PD patients who discontinue medication may experience a recurrence of depressed mood [52]. While dopaminergic medications can improve motor disturbances at night [129], a cross-sectional study has revealed that a higher dosage of dopaminergic medications may adversely impair sleep quality [116]. Furthermore, dopaminergic medications have been criticized for potentially causing sudden-onset sleep and daytime sleepiness [129]. Some medications, including amantadine and pramipexole, may also cause insomnia as a side effect [130].

On one hand, long-term dopaminergic treatments have been associated with dopamine dysregulation syndrome, leading to excessive doses and use of dopaminergic medications [129, 131]. On the other hand, continuous dopaminergic treatments have shown mixed results regarding sleep fragmentation. While some studies indicate these treatments can worsen sleep fragmentation [132,133,134], others have suggested that continuous dopaminergic treatments during the night can improve sleep quality by stabilizing muscle functions during sleep, leading to better sleep outcomes [135, 136]. For example, a study using wearable sensors quantitatively demonstrated the efficacy of nighttime apomorphine infusion in treating nocturnal hypokinesia in PD [136]. Therefore, the timing and dosage of dopaminergic drugs should be carefully considered [21, 137].

Diets

The quality of diet has been linked to sleep disturbance among PD patients with insomnia [138]. Several studies have suggested a potential association between the Mediterranean diet and a decreased rate of PD progression and onset [59], attributing the benefits to the anti-inflammatory and antioxidant properties of the diet [117]. Additionally, research conducted in the United States [60], China [61], and Greece [139] has shown a correlation between higher diet quality and a reduced likelihood of exhibiting prodromal PD features, with a specific study in Sweden observing this effect predominantly in individuals aged 65 and above [117]. Although the precise mechanisms by which the Mediterranean diet influences PD and its effect on PD are not fully understood, preliminary evidence suggests a beneficial connection. Given these findings, further research is needed to explore the relationship between diet quality and insomnia in PD to elucidate the underlying mechanisms.

Diagnosis of Insomnia in PD

The definition of insomnia has been a subject of controversy for a long time [125]. The main point of contention is whether a specific time threshold should be applied, how to differentiate insomnia from other sleep disorders, and how to assess the significance of sleep complaints for diagnosis. This may explain why some studies use vague terminology instead of explicitly referring to insomnia in their research. There are several classification systems for diagnosing insomnia, including the International Classification of Sleep Disorders, 3rd edition (ICSD-3) [22], the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V)[140], and the International Classification of Diseases, 10th revision (ICD-10) [141]. Insomnia diagnosis for ICSD-3 stratifies into chronic insomnia disorder, short-term insomnia disorder, and other insomnia disorders. The diagnostic criteria of DSM-V are demonstrated in Table 1.

Table 1 Diagnostic criteria of DSM-V
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The clinical diagnosis of insomnia in PD should involve a combination of clinical history, sleep quality–related questionnaires, and objective monitoring methods such as polysomnography (PSG) and actigraphy [137, 142, 143]. Clinically applied scales like the Pittsburgh Sleep Quality Index (PSQI) [46] and the Parkinson’s Disease Sleep Scale (PDSS-2) [144] can be used to diagnose sleep disturbances in PD. The diagnostic method begins with the patient’s subjective complaints of problems with initiating sleep, maintaining sleep, and early awakenings [145]. PSG has been recommended as an effective method of diagnosing insomnia while excluding other sleep disturbances in PD [145]. Besides, subjective questionnaires can be utilized as a rapid screening diagnosis. Therefore, a comprehensive evaluation of insomnia in PD requires considering various factors and utilizing appropriate diagnostic criteria and assessment tools.

Management Approaches for Insomnia in PD

The complexity of insomnia in PD underlined the importance of understanding the causes of insomnia and applying the appropriate treatment methods to best customize therapies for the patients. Emerging explorations on both non-medication treatment and medication treatment provide physicians and patients with opportunities to select treatments. While non-medication treatments are versatile for primary and secondary insomnia, medication treatments classify treatments for primary insomnia and secondary insomnia. These therapeutic options are summarized in Fig. 4.

Fig. 4
figure 4

Therapeutic options for treatments in insomnia in PD. This flowchart outlines the non-medication and medication therapies available for managing chronic, short-term, and primary and secondary insomnia in PD. Options include Cognitive CBT-I, pharmacological treatments, and combined approaches when necessary

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Non-medication Treatment

Managing insomnia in PD requires a comprehensive approach that includes both non-medication and medication treatments. The utilization of non-medication treatments should take into account the patient’s conditions, considering both their non-motor and motor symptoms. As a crucial component of the treatment strategy, non-medication approaches address these issues with minimal risk of side effects. Effective non-medication treatment includes cognitive-behavioral therapy for insomnia (CBT-I), exercises, bring-light therapy, non-invasive brain stimulation, deep brain stimulation, and other emerging therapies.

Cognitive-Behavioral Therapy for Insomnia

Cognitive-behavioral therapy for insomnia (CBT-I) is recognized as the most effective non-pharmacological treatment for insomnia, consisting of five key components: sleep consolidation, stimulus control, cognitive restructuring, sleep hygiene, and relaxation techniques [146]. In the management of insomnia related to mood conditions in PD, the focus is now put on non-pharmacological therapies.

The detailed components of CBT-I are as follows: (1) sleep consolidation aims to reduce patients’ worry about falling asleep, maintaining sleep, and waking up by eliminating excessive time spent in bed. By staying awake longer, patients’ sleep motivation increases, making it easier to fall sleep; (2) stimulus control assists patients associate their bed only with sleep and sex, separating it from other activities. If patients do not fall asleep within 10 min, they are instructed to leave the bedroom and engage in relaxing activities until they feel sleepy, then return to sleep; (3) cognitive restructuring involves changing negative thoughts about sleep into positive beliefs to improve sleep ability; (4) sleep hygiene consists of guidelines that promote high-quality sleep, including maintaining a consistent sleep schedule, avoiding food and drinks that can disrupt sleep, managing light exposure and screen time, engaging in regular physical activity and mindfulness, and creating a comfortable sleep environment; (5) relaxation techniques, such as meditation, can help calm the mind and nervous system, creating a relaxed mental state conducive to sleep [146].

A study examined the efficiency of CBT-I in the PD population with insomnia and found that PD patients who received CBT-I treatment showed a significant reduction in Insomnia Severity Index (ISI) scores compared to those who did not receive CBT-I (n = 12; p < 0.05). This study provides further evidence for the efficacy of CBT-I in treating insomnia in PD [147]. Another study reported improvements in total sleep time, sleep latency, and sleep efficiency after a 3-month CBT-I intervention [148]. Furthermore, the broad range of patients’ conditions indicates that CBT-I can be applied to PD patients with different levels of insomnia severity.

Exercises

A 6-month exercise intervention revealed that exercise is essential to improve sleep quality in the PD population [149]. Improved sleep quality had a positive impact on motor control, as participants exhibited enhanced motor skills the day after experiencing better sleep [150]. A review found that good sleep promoted dopaminergic functions, contributing to dopamine levels in the brain and enhancing motor control in PD patients [150]. Daytime exercises can also help improve sleep quality and duration by reducing daytime fatigue caused by poor sleep at night [146, 151, 152]. Higher-intensity exercises have shown more significant effects on sleep quality, as measured by PSG and objective sleep evaluation [153].

In addition to general exercise, specific types of exercises have been found to be beneficial for improving sleep quality in PD patients. These include aerobic exercises [154], resistance training [155], Qigong [156], yoga [157], Tai Chi [158], Brazilian Samba [159], multi-modal exercises [160], and an integrated approach of muscle and strength enhancement [153]. These exercises have retrospectively shown positive effects on boosting sleep quality among PD patients.

Bright-Light Therapy

Although bright-light therapy has traditionally been used for the treatment of depression, recent studies have shown its potential effect on both motor and non-motor symptoms in PD [92]. One study found that participants experienced improved sleep quality and ease of falling asleep after 2 weeks of bright light exposure to 10,000 lx, both in the morning (9–11 AM) and in the afternoon (5–7 PM). Both the treatment group (bright light 10,000 lx) and the placebo group (dim-red light 300 lx) reported a longer duration of sleep and a decreased wake time during onset sleep, indicating the effectiveness of bright-light therapy. However, it is essential to note that the placebo group may also show some effects, potentially due to the placebo effect or limited duration of treatment. While patients showed improvement in sleep after treatment, many patients were able to maintain up to half of the reduction in dopaminergic drug intake without losing control of symptoms, which offers hope for alleviating levodopa-triggered motor symptoms [161]. However, the researcher recommended a longer duration of treatment, such as 6 to 8 weeks, to fully observe the positive effect[162]. Bright-light therapy is believed to promote alerting mechanisms [163] during the daytime and actively impact the circadian system [95]. It may enhance circadian signaling and improve the consolidation of sleep–wake cycles in PD patients [92].

Deep Brain Stimulation

Deep brain stimulation (DBS) is a treatment for PD motor symptoms involving implanting electrodes in specific brain regions to deliver electrical stimuli. During PD treatment, improvements in sleep symptoms, including insomnia, have been observed in patients undergoing DBS[164, 165]. Despite its potential to improve sleep quality, further rigorous studies are needed to validate its efficacy. Insomnia in PD can be triggered by both motor and non-motor nocturnal symptoms during the night, such as tremors, painful dystonia, and nocturia [120, 121, 165]. DBS treatment can lead to improvements in these symptoms, resulting in an increase in total sleep time by about 1 h and a reduction in sleep fragmentation [165]. Objective measures of sleep, such as sleep latency and waking after sleep onset, also demonstrate improvement post-DBS treatment, indicating faster sleep onset and longer sleep duration [165]. Additionally, studies have reported improved sleep quality among patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and globus pallidus internal deep brain stimulation (GPi-DBS) [166, 167]. However, the impact of STN-DBS on nocturnal non-motor symptoms remains unclear, as its primary mechanism appears to be alleviating motor symptoms that indirectly affect sleep quality [168, 169]. These improvements in motor symptoms may contribute to relieving associated insomnia symptoms, such as fragmented sleep and reduced sleep time.

Despite some studies reporting improved sleep functions and reduced insomnia in PD patients undergoing DBS, potentially due to DBS or a decrease in dopaminergic medication, it is important to note that DBS is primarily used for managing motor symptoms in PD, and its effects on sleep conditions require further investigation. Further research is necessary to evaluate the potential benefits of DBS for PD patients with nocturnal motor symptoms and sleep dysfunction [170].

Other Emerging Therapies

There are other therapies that have proven effective for PD patients with sleep disturbances. Zhu et al. examined the effectiveness of biofeedback therapy in 26 patients and found a significant improvement in objective and subjective sleep quality after 3 weeks of treatment (5 times a week) [171]. Biofeedback therapy has also been shown to alleviate cognitive conditions, mood-related disorders, and psychogenic problems [172].

Another physical therapy, Photobiomodulation Therapy (PBMT), which includes the use of a He–Ne laser, has also been proven effective in treating insomnia. Several studies conducted in China observed enhanced sleep duration, reduced sleep latency, and improved sleep efficiency without potential adverse effects compared to medical treatments [173,174,175,176]. The mechanism behind the improvement in sleep quality is believed to be an increased serum level of melatonin that regulates circadian rhythms [177]. Additionally, homeostasis, mediated by the blood circulatory system, is also suspected to play a role [178]. In addition to the benefits of sleep, recent animal models have also shown the antidepressant effects of PBMT, which could be used in future depression treatment [179]. Furthermore, low-intensity pulsed ultrasound treatment (LIPUS) [180] and music therapy [181] may also be applied to patients with insomnia.

Medication Treatment

Primary Insomnia

Insomnia in PD can include primary insomnia, which is not directly caused by PD itself but shares similarities with insomnia in the general population. Therefore, managing primary insomnia often involves approaches similar to those for non-PD populations, tailored to the specific needs and conditions of PD patients. Additionally, evidence supporting the efficacy of commonly used insomnia medications in PD primarily stems from studies involving non-PD populations [170].

Recommended treatment options for primary insomnia, as outlined by Chinese experts’ consensus [182] and pharmacotherapy guidelines for insomnia [183], include the following sequences: (1) short- or medium-term courses of benzodiazepine receptor agonists (BzRAs), such as non-benzodiazepines (non-BZDs) and BZDs, are recommended for managing insomnia [184, 185]. While several studies have found an association between long-term use of BzRAs and cognitive decline, prescriptions should only be applied under appropriate indications [183, 186,187,188,189,190]. Common non-BZDs used for insomnia in PD patients are eszopiclone and dexzopiclone, which have been proven safe and effective [184, 191, 192]. Dexzopiclone use should be monitored closely in older adults with cognitive and motor impairments [191]. (2) melatonin receptor agonists (MRAs) such as melatonin sustained–release tablets and ramelteon are also frequent options, generally demonstrating efficacy and safety but requiring cautious use [193]. (3) Orexin receptor antagonists (ORAs) like suvorexant, a highly selective orexin receptor antagonist approved by the FDA for insomnia treatment, promote sleep by blocking the orexin receptor, thereby reducing sleep latency, awakening time after sleep, and increasing total sleep time. It is considered safe with no adverse effects on morning motor performance[194]. Other treatments, such as over-the-counter antihistamines, may be used for insomnia, but their effectiveness and safety in PD patients remain unclear. (4) Melatonin: Although melatonin has been investigated for its anti-inflammatory and antioxidant properties [195,196,197,198], its role in neuroprotection, particularly in PD, is still under investigation and not yet established [199,200,201,202]. However, clinical studies have reported significant improvements in both subjective and objective sleep quality in PD patients with insomnia following melatonin treatment [203,204,205]. It is important to note that melatonin is not routinely used as a medication for PD but primarily for managing sleep disturbances.

Secondary Insomnia

Secondary insomnia in PD can arise from comorbidities related to motor symptoms and non-motor symptoms. Strategies to improve sleep quality in PD patients by alleviating nighttime motor symptoms are similar to those used for managing daytime motor disturbances. One approach involves administering long-acting medications that provide a sustained therapeutic effect throughout the night. Treatment methods are tailored to address both motor symptoms and non-motor symptoms.

Common motor symptoms contributing to insomnia include nocturnal akinesia, rigidity, and tremors, which harm nighttime sleep quality. The following are the classifications of treatment for comorbidities with motor symptoms. (1) Levodopa treatment: controlled-release formulations of carbidopa-levodopa taken at bedtime have been shown to improve nocturnal akinesia. However, their primary function is not to improve objective sleep measurements [17, 206]. (2) Non-ergot derivatives of dopamine receptor agonists (DAs), such as pramipexole, piribedil, ropinirole, and rotigotine, have been investigated for their effects on nocturnal and early morning motor fluctuations in PD. DAs directly stimulate dopamine receptors in the brain to produce their impact. While their efficacy in controlling symptoms may not be as strong as carbidopa-levodopa, they have a long-lasting effect and can be used in combination with levodopa to stabilize the fluctuations in their efficacy. Clinical research has found the effectiveness of pramipexole [207, 208], piribedil [209], ropinirole [210], apomorphine [211], and rotigotine [207, 212] in improving overnight tremors, dystonia, and sleep issues in PD patients, leading to improvements in both objective and subjective sleep quality. However, it is worth noting that the role of dopamine receptor agonists in depression treatment has also been studied [209, 213]. (3) Monoamine oxidase B (MAO-B) inhibitors, such as rasagiline and safinamide, are utilized to potentially prevent dopamine neuron degeneration and maintain dopamine levels in the brain. These inhibitors have shown benefits in ameliorating nocturnal tremor and restlessness in PD patients, as assessed by the Parkinson’s Disease Sleep Scale (PDSS) [214]. Adjunctive use of rasagiline has been found to significantly enhance patients’ ability to initiate sleep and reduce nocturnal awakenings [215]. Similarly, safinamide is employed to improve motor function and manage fluctuations, with a general recommendation to administer it after breakfast and lunch to mitigate potential sleep disturbances, as taking it late in the day could exacerbate insomnia symptoms [216]. However, it is crucial to recognize that MAO-B inhibitors, particularly when combined with certain food or other medications such as antidepressants, can lead to adverse reactions and have implications for overall health [217]. Therefore, it is important for patients to consult with their doctors before taking any additional medications that interact with MAO-B inhibitors. Therefore, patients should consult their healthcare providers before initiating any additional medications that interact with MAO-B inhibitors. Patients should also receive guidance on the optimal timing of medication intake to minimize potential side effects related to sleep disturbances. (4) Catechol-O-methyltransferase (COMT) inhibitors, used as adjuvant therapy for levodopa, work by inhibiting the activity of the COMT enzyme, which helps suppress the peripheral metabolism of levodopa. This helps maintain the concentration of levodopa in the brain and may alleviate motor symptoms at night, thereby improving sleep quality [215]. (5) Amantadine: known to promote the generation and release of dopamine at the nerve endings and prevent its reabsorption, helping maintain dopamine levels. This action can contribute to mitigating rigidity and tremors in PD patients, which might theoretically improve sleep quality by reducing motor symptoms that can disrupt sleep [218]. However, it is important to note that amantadine also carries side effects such as insomnia, which could potentially counteract its benefits in improving sleep [219, 220]. To mitigate the risk of insomnia, it is recommended that amantadine be taken no later than 4 PM [221]. Therefore, while amantadine may aid in managing motor symptoms, its tendency to induce insomnia needs to be carefully considered.

Non-motor symptoms, such as mood disturbances, nocturia, and pain, contribute significantly to secondary insomnia in PD. Mood-related issues, particularly depression and anxiety, also play a crucial role in impacting sleep quality among PD patients. Various treatment options for depression and anxiety have been highlighted [222]. (1) selective-serotonin-reuptake inhibitors (SSRIs): These medications, like sertraline and fluoxetine, are commonly prescribed to manage both depression and anxiety. Sertraline has demonstrated efficacy in treating both conditions safely [223,224,225]. Fluvoxamine can enhance REM sleep latency period and improve sleep quality in patients with depression and anxiety [226]. (2) serotonin-norepinephrine reuptake inhibitors (SNRIs): Examples such as venlafaxine and duloxetine are effective in treating mood disorders with minimal side effects [227, 228]. (3) Several antidepressants with sedative effects, including trazodone, mirtazapine, and doxepin, are also considered. Trazodone is suitable for patients with depression, severe sleep apnea syndromes, or a history of medication dependence [229]. Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is commonly used to improve sleep quality by increasing sleep duration and shortening sleep latency [230, 231]. Doxepin, FDA-approved for the treatment of insomnia, is primarily used for patients struggling with sleep maintenance and short-term sleep issues, proving safe with minimal risk of dependence among the elderly [232, 233]. (4) Buspirone, a specific anxiolytic medication, effectively manages anxiety symptoms without the sedative effects often associated with other anxiolytics [234]. (5) Additionally, combined therapy using BzRAs/MRAs and antidepressants is recommended to address sleep disturbances by targeting different sleep mechanisms and alleviating mood-related symptoms to enhance overall sleep quality. However, caution is advised when using combined therapy due to potential side effects associated with BzRAs/MRAs and antidepressants [235, 236].

For nocturia, which affects approximately 35% of PD patients and significantly contributes to nocturnal awakenings and difficulty falling asleep [17, 37], various interventions have been explored. Behavioral approaches such as limiting late-night fluid intake and appropriate diuretic use can provide some relief. However, medical treatments are often necessary for more effective management [237, 238]. (1) Antimuscarinic medications: Solifenacin and trospium are antimuscarinic medications that minimally penetrate the central nervous system, thereby reducing the risk of cognitive impairment. Clinical trials have demonstrated their effectiveness in reducing incontinence episodes and nocturia events in PD patients, establishing them as safe treatment options [239,240,241,242]. (2) Beta-3 adrenergic agonist: Mirabegron has similarly shown efficacy in significantly decreasing the frequency of nocturia episodes in PD patients with a favorable safety profile and minimal adverse effects [243,244,245]. While these medications provide beneficial effects, monotherapy may not be sufficient for all PD patients experiencing nocturia. Therefore, urological consultation is often recommended to consider combined treatment strategies, which may include botulinum toxin injections or addressing concurrent conditions such as benign prostatic hyperplasia, which can exacerbate urinary symptoms [237].

Across various studies, approximately 40–95% of PD patients experience pain that can impact sleep quality [246,247,248,249]. Management of pain in PD includes dopaminergic and non-dopaminergic treatment. Dopaminergic treatment manages pain by addressing conditions like rigidity, dystonia, akinesia, and dyskinesia [250]. When dopaminergic therapy is insufficient, general pain management becomes essential. Patients may suffer from either neuropathic or other types of pain during the night, contributing to insomnia. In such cases, it is necessary to consult physicians for the management of general pain.

Impact on Public Health

The HRQoL of PD patients with insomnia has been greatly impacted [30, 31, 251], and the consequences of sleep disturbances in PD patients may extend to their employment. However, limited research has been conducted on this subject. While much attention is placed on patients, the caregivers and social implications are often overlooked.

Informal caregivers, also known as care partners, typically consist of family members and friends who provide physical and mental support in home settings [252]. These care partners often take on responsibilities that would otherwise be carried out by the national health systems [253]. Despite the estimated support of over $375 billion provided by care partners, the enormous mental and financial burdens they face are often disregarded [252]. A study on the treatment of insomnia in PD briefly mentions the association between caregiver burden and depression with patients’ sleep quality, but does not further explore the impact on caregivers [184]. However, several studies have revealed that the prevalence of depression among caregivers ranges from 11 to 35% [253,254,255]. In addition, a study indicated that the highest psychological conditions among caregivers are depression (17.8%) and insomnia (14.9%), with these conditions steadily increasing during a 1-year follow-up [256]. Caregivers not only bear physical and mental burdens generated by patients experiencing psychotic symptoms, cognitive impairment (dementia), and non-motor symptoms like sleep disorders, but they are also at risk of being diagnosed with anxiety [253].

On the other hand, care partners and patients experience the influence of reciprocity [257]. Reciprocity, characterized by mutual concerns and intimacy, indicates their interpersonal relationship [258]. Depression and insomnia are common conditions in both PD patients and caregivers [259]. A high level of reciprocity is linked to less depression and caregiver burdens, while the progression of PD significantly aggravates the reciprocity [257]. However, while patients are more likely to be diagnosed with mental disorders, caregivers are often underdiagnosed or refuse to seek help, which is not conducive to the well-being of both patients and care partners [254]. Furthermore, care partners who struggle with insomnia also experience more daytime fatigue. They have to cope with the progression of the disease and the negative impacts of the disease and its treatments, potentially straining caregiving relationships and triggering higher levels of depression and anxiety [256].

Moreover, the onset of certain motor symptoms in PD patients may worsen the sleep quality of care partners and even pose a threat to their lives. The socioeconomic status and health conditions of caregivers have been found to increase the burden on care partners [259]. On a societal level, the perception of social support and isolation from social engagement and community negatively influence the burdens faced by care partners [260]. It is crucial to recognize the reciprocal nature of the relationship between PD patients and their care partners and to address the mental health and well-being of both parties. Providing support and resources for caregivers, as well as promoting social engagement and community involvement, can help alleviate the burdens they face and improve the overall quality of life for both patients and care partners.

Conclusions and Future Directions

While there are no regional disparities in the co-occurrence of insomnia in PD globally, different studies have used various criteria to establish the correlation between PD and insomnia. It is important to establish standardized criteria for researchers to use in order to ensure consistency in future studies. Additionally, further research is needed to explore the occurrence of insomnia in PD and how factors such as race, genes, and environment may influence the results. This review has discussed various pathophysiological mechanisms, comorbidities, and risk factors. However, each of these areas requires further investigation, given the complexity of factors and predictors that contribute to the progression of PD. Neurodegenerative changes, basal ganglia beta oscillations, and circadian rhythms have been implicated, but their molecular mechanisms need to be better understood through future research.

Current research has primarily focused on the pharmacological management of insomnia in PD, with less attention given to non-pharmacological interventions. Limited understanding has been achieved in identifying the obstacles and most applicable sub-populations when patients apply CBT-I. While initial research into the therapeutic effects of bright-light therapy has shown some promising results, further investigations should be undertaken to assess the efficacy of prolonged bright-light therapy and evaluate the impact of longer treatment durations. Furthermore, it is important to consider a combination of pharmacological and non-pharmacological management approaches to improve the overall health of patients. Currently, pharmacological management is primarily based on the treatment of motor symptoms in general PD patients and insomnia guidelines in the non-PD population. There is no specific consensus or recommendations established for treating insomnia in PD. Future research should focus on systematically evaluating the efficacy and safety of medications within this population.

In consideration of public health, limited research has been conducted to investigate how insomnia in PD influences public health and social burdens. There has been less attention given to caregivers, who also struggle with PD conditions and comorbidities. Understanding this aspect could have significant implications for interventions aimed at improving the quality of life for both patients and their caregivers. It is important to better understand the social burdens of insomnia in PD in order for policymakers to effectively implement policies to improve the situation.

In conclusion, insomnia is a common and significant non-motor symptom of PD. It affects a large proportion of PD patients and can have a negative impact on their quality of life. The prevalence of insomnia in PD varies across different geographic locations due to genetic, environmental, and gender discrepancies, as well as differences in diagnosis criteria. Understanding the mechanisms underlying insomnia in PD, as well as identifying risk factors and comorbidities, is crucial for effective management and treatment. Both nonpharmacologic and pharmacologic therapies should be considered, and further research is needed to explore the long-term outcomes of insomnia in PD. By addressing the challenges posed by insomnia in PD, we can improve the overall well-being of patients and their caregivers, and ultimately enhance the management of this complex neurodegenerative disorder.