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Sleep and Neurodegenerative Disorders
Introduction
There is a significant burden of neurodegenerative disorders globally, and it is expected to increase with a rise in the older adult population. Sleep disturbances in these patients are primarily related to the neurodegenerative condition and add to the morbidity caused by the disorder itself.[1] The relationship between sleep and neurodegeneration is bidirectional. Neurodegenerative disorders can impact brain regions that control sleep, while sleep disturbances can accelerate or worsen neurodegeneration by impairing protein clearance and increasing oxidative stress.[2]
Along with managing the primary neurodegenerative disorder, managing sleep complaints in affected patients remains challenging. These patients may experience insomnia, hypersomnia, rapid eye movement (REM) sleep behavior disorder (RBD), obstructive sleep apnea (OSA), and restless legs syndrome (RLS), among other disturbances. Management of sleep disorders in patients with neurodegenerative conditions may improve sleep-related symptoms of the disease and overall quality of life. This activity discusses the etiology, epidemiology, clinical manifestations, evaluation, and treatment of sleep disorders in 2 of the most common neurodegenerative diseases: Parkinson disease and Alzheimer disease.
Etiology
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Etiology
Sleep disturbances are common in patients with Parkinson and Alzheimer diseases, significantly impacting their quality of life. Understanding the specific types of sleep disorders associated with these neurodegenerative conditions is essential for effective diagnosis and management.
Sleep Disorders in Parkinson Disease
Sleep disorders are prevalent in individuals with Parkinson disease, with insomnia, hypersomnia, and RBD being the most frequently occurring disorders.
Insomnia
Insomnia is a prevalent issue among individuals with Parkinson disease, and it is often exacerbated by multiple contributing factors as follows:
- Motor symptoms such as muscle cramps and nighttime stiffness can lead to sleep-onset and sleep-maintenance insomnia.[3]
- Autonomic disturbances such as nocturia can lead to sleep-maintenance insomnia.[4]
- Levodopa/carbidopa used for treatment can have a potential adverse effect on insomnia.[5]
- Associated mood disorders such as depression can have insomnia as a presenting symptom.[6]
- Associated OSA, RLS, or circadian rhythm sleep disorders (CRSD) in individuals with Parkinson disease can exacerbate or overlap with insomnia symptoms.[7]
Both motor symptoms, such as tremors, lack of movement, and pain, as well as non-motor symptoms, including frequent urination, can disrupt sleep in affected patients. Moreover, recent research has shifted its focus toward exploring the intrinsic causes of the disease itself as a potential contributor to insomnia in patients with Parkinson disease, including neurodegeneration of brainstem sleep centers.[8]
Hypersomnia
There are several factors contributing to an association between excessive daytime sleepiness and neurodegenerative disorders. These factors include the following:
- Sleep-related symptoms in patients with Parkinson disease may be due to potential adverse effects of medications such as dopamine therapy.[9][10]
- Loss of hypocretin neurons through alpha-synuclein degeneration may contribute to the common sleepiness symptoms.[11]
- Associated sleep-disordered breathing (SDB), RBD, or CRSD, can exacerbate excessive daytime sleepiness in individuals with Parkinson disease.[12]
- Excessive daytime sleepiness may be associated with caudate denervation in those with Parkinson disease.[13]
REM sleep behavior disorder
Parasomnias, including RBD, occur frequently in association with α-synucleinopathies. Alpha-synuclein pathology leads to hypocretin neuron damage in Parkinson disease and other synucleinopathies such as multiple system atrophy and dementia with Lewy bodies.
Obstructive sleep apnea
A high incidence of both central sleep apnea and OSA is found in patients with Parkinson disease due to the contribution of several factors, such as rigidity, diaphragmatic dyskinesia, stridor, and increased tone in upper airways.[14]
Sleep Disorders in Alzheimer Disease
Sleep disturbances are a common issue among patients with dementia in general, particularly those with Alzheimer disease. One well-known occurrence of dementia is sundowning, which is the exacerbation of delirium at night and is often linked to sleep disturbances. Sundowning is identified by symptoms such as agitation, confusion, and irritability as natural light diminishes into the evening and at night. Individuals with dementia frequently experience excessive daytime sleepiness and nighttime insomnia. Sleep loss and reduced REM sleep in tauopathies, such as Alzheimer disease, can lead to insomnia and are believed to be due to the degeneration of sleep-promoting regions of the brain.[15] Impaired amplitude and delayed acrophase of the circadian rhythm in otherwise healthy older individuals increase the risk of developing Alzheimer disease.[16]
Some of the other contributing factors for the increased association between Alzheimer and CRSD are related to the following:
- Degeneration of suprachiasmatic nucleus neurons leads to a reduction in melatonin levels, a hormone secreted by the pineal gland. As individuals age, the start of melatonin secretion tends to occur earlier, and its peak becomes less regular. This may be attributed to the degeneration of the suprachiasmatic nucleus, as the pineal gland appears unaffected by Alzheimer disease pathology.[17] The alteration of melatonin levels and the significant reduction in exposure to zeitgebers can result in CRSD in patients with Alzheimer disease. This can lead to both excessive daytime sleepiness and nighttime insomnia.
- Underlying psychiatric disorders such as depression or anxiety can lead to daytime sleepiness and nighttime insomnia.
- Insufficient light during the day or excessive light at night before bedtime can also play a role.[18][19]
In addition, individuals with Alzheimer disease may have a slightly increased risk of developing SDB, likely due to the deterioration of central respiratory control regions in the brainstem.[20] OSA is known to exacerbate the cognitive decline in those with Alzheimer disease. Positive airway pressure therapy has been shown to alleviate this decline in mental function.[21]
Epidemiology
In 2016, 6.1 million individuals globally were diagnosed with Parkinson disease, a number increasing with the aging population. The estimated prevalence is 94 cases per 100,000 people, with an annual incidence of 8 to 18.6 per 100,000 person-years.[22][23] The disease's occurrence rises with age, showing no significant difference in sex. The overall prevalence, adjusted to the European standard population, is 1.6 per 100 people. Results form one study reported prevalence rates by age group: 0.6 for those 65 to 69, 1.0 for 70 to 74, 2.7 for 75 to 79, 3.6 for 80 to 84, and 3.5 for individuals 85 to 89.[24]
Sleep problems are prevalent in individuals with Parkinson disease, with up to 98% experiencing them at some point.[16] Common sleep disorders in this population include insomnia, hypersomnia, and RBD.[25] In a survey of non-motor symptoms, 64% of patients reported sleep problems. RLS occurs in 15% to 20% of patients with Parkinson disease, though early-life RLS does not predispose individuals to develop Parkinson disease later.[26][27] However, severe RLS can be an early sign of Parkinson disease.[28] Both conditions are linked to periodic limb movements during sleep.[29] RBD is present in about 46% of patients with Parkinson disease.[30]
The coexistence of SDB and Parkinson disease has been reported in the literature in variable frequency (prevalence between 27% and 73%).[31][32] Even though several studies have indicated that many patients with Parkinson disease experience SDB, the reported prevalence varies due to various factors, such as different definitions of respiratory events, severity thresholds of the disease, or diagnostic methods employed.[33][34] This variability in reported prevalence is explained by heterogeneity in sample size, disease severity, and diagnostic definition and testing modality. For example, using standard diagnostic polysomnography (PSG) in a retrospective series of 49 patients with Parkinson disease, at least 21 patients (43%) had OSA diagnosed (apnea/hypopnea index [AHI] ≥5 events/hour).[35]
Globally, more than 55 million people are estimated to have dementia, and Alzheimer disease accounts for 60% to 70% of the cases. The prevalence of insomnia in affected individuals is >50%.[36] Results from a study demonstrated that over 90% of the 174 patients with RBD, as confirmed by PSG, will develop a neurodegenerative disease within 14 years of their RBD diagnosis.[37] The median time to diagnosis for these patients was 7.5 years.
Pathophysiology
Understanding the pathophysiology of Parkinson and Alzheimer diseases is crucial for developing effective treatments. Both disorders involve complex neurodegenerative processes that affect brain function and structure, leading to progressive cognitive and motor impairments.
Parkinson Disease
In Parkinson disease, symptoms such as hypersomnia can occur due to damage to wake-promoting areas of the brain (locus coeruleus, raphe nucleus, hypocretin neurons) through alpha-synuclein degeneration.[38] In the natural history of synucleinopathies such as Parkinson disease, there is early involvement of pontine and medullary nuclei that control REM sleep, which results in RBD, which is highly characteristic of alpha-synuclein neurodegeneration.[39]
Alzheimer Disease
As individuals age, their suprachiasmatic nucleus and hippocampus suffer from degeneration (that does not affect the pineal gland), leading to disrupted CRSD manifesting by earlier awakening and reduced consolidation of nocturnal sleep.[16] The pathologic hallmark of Alzheimer disease is the accumulation of beta-amyloid plaques and neurofibrillary tangles composed of tau. Alzheimer disease leads to the degeneration of the nucleus basalis of Meynert, pedunculopontine tegmental and laterodorsal tegmental nuclei, and noradrenergic neurons of the brainstem, leading to reduced REM sleep.[40] In a study that analyzed autopsies of 172 cases with confirmed RBD, the results found that 170 of the cases had a neurodegenerative disease. The most common clinical diagnosis among these cases was dementia with Lewy bodies, which accounted for 57% of the diagnoses, followed by Parkinson disease, which accounted for 19% of the diagnoses.[41]
History and Physical
A thorough history and physical examination are essential for evaluating sleep disorders in patients with neurodegenerative diseases. This comprehensive assessment helps identify the specific sleep disturbances and their impact on the patient's overall health and quality of life.
Parkinson Disease
Patients with Parkinson disease may present with various nonspecific complaints such as daytime sleepiness, loud snoring, insomnia, cognitive deficits, mood changes, and morning headaches. However, patients with Parkinson may present with difficulty initiating sleep and staying asleep or isolated excessive daytime sleepiness.[42][43] Taking a good history, including a complete list of medications and over-the-counter drugs, is important as presenting symptoms could be due to an adverse effect of dopamine therapy initiated for motor symptoms.[44]
Hypersomnia (self-reported type) is very common among individuals with Parkinson disease, affecting more than half of these patients.[45] Among individuals reporting sleepiness, severe hypersomnia occurs in a significant 50% of cases. Furthermore, 39% exhibited stage REM sleep during at least 2 naps, a characteristic common among those with narcolepsy.[33]
Sleep attacks are also common among individuals with Parkinson disease (up to 43% of cases affected).[46] These sudden bouts of drowsiness can be particularly dangerous, as nearly 1 in 5 have experienced them while driving. Sleep attacks are linked to dopaminergic therapy, particularly dopamine agonists and levodopa. The impact of dopamine agonists on sleep attacks is most substantial in men younger than 70 years of age, and some of these drugs have been shown to reduce orexin-A levels, which could potentially explain their connection to sleep attacks.[46] Patients should be screened for other associated conditions affecting sleep, such as depression, OSA, RBD, and RLS. Non-familial RLS can be seen commonly in patients with Parkinson disease.[27]
Repeated episodes of sleep-related vocalization and complex motor behaviors that occur during sleep should increase the suspicion of RBD in patients with Parkinson disease. These movements may involve kicking, grabbing, smiling, and shouting, potentially injuring the bed partner.[42] When awoken from the event, the patient returns to normal consciousness.
Examination findings may show a narrow oropharynx, obesity, and large neck circumference (>17 inches in men, >16 inches in women). In addition, a physical exam may demonstrate findings of the neurodegenerative disorder itself, such as postural instability or gait abnormalities. Cognitive impairment and executive dysfunction are also seen.[47]
Alzheimer Disease
Patients with Alzheimer disease may present only with cognitive function decline or commonly with difficulty initiating and or maintaining sleep that affects their family.[48] Most patients with Alzheimer disease present with sleep-wake irregularities caused by disruptions in circadian rhythms. Usually, there are changes in sleep architecture that are similar to those observed in older adult populations but are more pronounced in severity. The typical CRSD seen in older adults is earlier awakening and reduced consolidation of nocturnal sleep with multiple napping.[16]
Physical examination may show abnormal mental status with impaired memory, concentration, and attention. Furthermore, in patients with Alzheimer disease, due to the significantly disrupted sleep, agitation and sundowning during nighttime are frequently encountered problems. However, underlying medical comorbidities should be screened, which could contribute to sleep disturbances such as RLS. In addition, given that OSA can worsen with age and Alzheimer disease, it is important to assess for clinical findings such as snoring, excessive daytime sleepiness, and physical findings during examination.[21] Establishing a diagnosis based on symptomatology can be difficult in Alzheimer patients, especially when the degree of dementia is advanced.
Evaluation
Evaluating sleep disorders in patients with neurodegenerative diseases involves a comprehensive approach, including detailed clinical assessments and diagnostic tests. A thorough evaluation is crucial for identifying specific sleep issues and tailoring effective management strategies.
Evaluation of Sleep Disorders in Parkinson Disease
Insomnia
In patients with Parkinson disease, a detailed evaluation is warranted to identify a potential contributor to insomnia. Patients should be asked about the presence of any motor symptoms at night (cramps, stiffness, or impaired turning in bed), autonomic symptoms such as nocturia, presence of concomitant mood disorder, sleep apnea, or RLS. A history of recent dose adjustments in medications for Parkinson disease should also be obtained. If the patient has difficulty providing a history, sleep logs, diaries, and sleep trackers may be helpful. Self-reported screening tools could be used through validated questionnaires such as the Pittsburgh Sleep Quality Index (PSQI) and sleep problems questionnaire.[49][50] In patients with Parkinson disease-associated insomnia, Parkinson disease-specific screening questionnaires such as Parkinson Disease Sleep Scale-2 (PDSS-2) or Scales for Outcomes in Parkinson disease-SLEEP can be used.[51] Evaluation tools such as the STOP-Bang score help determine the probability of OSA.[52]
PSG is a valuable tool if insomnia is thought to be secondary to OSA or other forms of sleep disorders, such as movement disorders or parasomnia; this tool may reveal a reduction in total sleep time, sleep efficiency, stage 2 (N2) percentage, slow wave sleep, REM percentage, and an increase in REM latency and sleep latency.[53]
REM sleep behavior disorder
The bed partner or caregiver is asked about symptoms of dream enactment behavior. In individuals suspected to have RBD, laboratory video and PSG with RBD montage (extra EMG recording from upper extremities) are essential for confirming the diagnosis. REM sleep without atonia is required for the diagnosis; this can also help evaluate concomitant OSA or periodic limb movement disorder.[54]
Restless legs syndrome
In RLS, there is an urge to move the legs due to an uncomfortable sensation, which is worse during the evening and rest periods and is relieved by movement. The patients also have nocturnal leg cramps, which need to be distinguished from typical RLS. The symptoms in RLS should follow a diurnal variation and are relieved by movement.[55]
Hypersomnia
The patient should be evaluated for the presence of sleep attacks or sudden onset sleep. Evaluation of other primary sleep disorders, such as OSA, RLS, and insomnia, should be pursued. History of recent initiation of dopamine therapy should also be obtained as hypersomnia can present as an adverse effect of these medications.[18]
Sleep-disordered breathing
Some of the challenges in diagnosis are related to the presence of Parkison disease-related comorbidities such as upper airway dysfunction, neurodegeneration of central sleep/wake areas, coexistence with RBD, and frequent use of central nervous system-altering pharmacological therapies; therefore, standard PSG studies are recommended to confirm the diagnosis, but many patients with Parkinson disease with a disability may not have access to these studies. Home sleep apnea tests (HSAT) offer a simpler method to diagnose SDB; however, these devices have not been validated in patients with Parkinson disease and may not be sensitive enough to detect central alveolar hypoventilation or central SDB.[56] Some HSATs, such as WatchPAT, which use tonometry technology, have been validated to identify central sleep apnea in adults.[57]
Evaluation of Sleep Disorders in Alzheimer Disease
Insomnia
Inquiring about sleep disturbances in patients with dementia on routine clinic visits is helpful. A detailed history of sleep schedules may be needed to arrive at the diagnosis. History regarding outdoor time exposure, caffeine, alcohol, smoking, presence of nighttime disturbances (especially in a nursing home), and physical activity needs to be obtained. Additional evaluation regarding RLS, periodic limb movement disorder, and OSA is also needed if it is potentially contributing to insomnia. PSG is recommended when there is a high suspicion of OSA, narcolepsy, or periodic limb movement disorder. Similar to the general population, OSA commonly occurs with insomnia with a bidirectional relationship (eg, COMISA).[58][59] Therefore, low suspicion and early evaluation are needed to identify COMISA. On the other hand, PSG is not required for the evaluation of isolated insomnia or sleep-wake disorders such as CRSD, as these can be assessed clinically and occasionally with the use of actigraphy.[60]
Circadian rhythm disorder
Patients with Alzheimer disease have a high prevalence of CRSD, particularly irregular sleep-wake rhythm.[61] Questions about nighttime confusion and agitation, commonly known as sundowning, should be included in the assessment. In CRSD, prolonged sleep latency and later wake times are reported in delayed sleep-wake phase disorder.
Obstructive sleep apnea
Diagnostic evaluation should be performed on patients with excessive daytime sleepiness, nighttime snoring, or complications associated with sleep apnea. Some of the standard evaluation tools include the STOP-Bang questionnaire and the Epworth Sleepiness Scale. In-laboratory PSG is considered the gold standard test. An HSAT could be considered in patients with a high pretest probability of moderate to severe sleep apnea, suggested by daytime hypersomnolence, habitual snoring, witnessed apnea, gasping, or choking during sleep.[62]
Treatment / Management
Treating sleep disorders in patients with neurodegenerative disease requires a multifaceted approach aimed at improving quality of life and managing associated symptoms; this involves integrating pharmacological interventions, behavioral therapies, and lifestyle modifications tailored to address the unique challenges posed by the neurodegenerative condition and the specific sleep disorder.
Insomnia
Proper identification of the underlying sleep disorder, sleep hygiene, and good sleep habits are recommended in all patients with insomnia. Cognitive behavioral therapy for insomnia is strongly recommended as a first-line therapy for insomnia associated with all conditions.[63] (A1)
If motor symptoms are interfering with sleep in a patient with Parkinson disease, a trial of dopamine therapy in the form of short- or long-acting carbidopa/levodopa or dopamine agonists is recommended. If the dopamine agent is suspected to cause insomnia, a decrease in dose or change in the timing of doses can be attempted first.[64]
In Alzheimer disease patients, making environmental changes should be the first step towards management. Especially for patients living in a nursing home, it is recommended to keep the environment dark at night and to reduce nighttime noise and nocturnal awakenings for medications or vital signs.[65] These patients also need to be screened for the use of medications that can potentially cause insomnia, such as antipsychotics and stimulants. The consistency of the sleep-wake cycle also needs to be maintained. Early morning bright light therapy combined with physical activity is an effective intervention for consistent wake time.[66] In patients with dementia, there is no evidence of the efficacy of pharmacologic agents such as melatonin, trazodone, antihistamines, or antipsychotics for the treatment of insomnia.[67] In general, benzodiazepine should be avoided in cases of insomnia associated with Alzheimer disease due to the associated risk of falls and altered mental status.[68](A1)
Circadian Rhythm Disorders
Circadian disruptions are a significant factor in the development of insomnia among older adults in general, and this is true even in cases where cognitive decline is not present. Neurodegenerative changes can also contribute to these issues, which can lead to worse symptoms, including insomnia. Maintenance of sleep-wake schedules is the first step in its management. Waking up at the same consistent time should be advised if the patient wants to take multiple naps during the daytime. Evening bright light therapy is recommended for advanced sleep-wake phase disorder. In delayed and irregular sleep-wake phase disorder, bright light on awakening in the morning and evening melatonin several hours before the desired bedtime is the recommended treatment option.[18]
Bright light therapy is performed by delivering a high circadian stimulus during the day (circadian stimulus >0.3 or >400 lux at the eye of a bluish-white light) and low circadian stimulation during the evening (circadian stimulus <0.1 or <50 lux at the eye of yellowish-white light).[69] Light boxes can also be used as a form of therapy. The recommended duration is 30 minutes for the box producing 10,000 lux and 2 hours for the box producing 2500 lux.[70][71]
Restless Legs Syndrome
Measurement of iron studies is the first step, and iron replacement is recommended if the ferritin level is <75 ng/mL. In patients with Alzheimer disease, treatments include dopamine agonists (such as pramipexole), and alpha-2-delta ligands (such as gabapentin, and pregabalin).[72] In Parkinson disease, if the RLS symptoms coincide with nighttime motor symptoms, a long-acting dopamine agonist or levodopa is used. Otherwise, the treatment remains the same with gabapentines, especially in patients already receiving dopaminergic medications. In cases that are resistant to these treatments, opioids or deep brain stimulation may be considered.[73](B2)
Hypersomnia
Treatment should begin with behavioral counseling about sleep hygiene and evaluating other contributing disorders such as OSA, RLS, or psychiatric conditions. Bright light therapy and exercise are recommended as an initial step in all patients with hypersomnia.[74][75] In individuals with Parkinson disease, the initial management involves reducing dopamine agonists or levodopa, especially for patients on higher doses.[76] When these conditions are ruled out, treatment options include modafinil, methylphenidate, and sodium oxybate, with careful monitoring of comorbid psychiatric conditions to prevent agitation and confusion.[77](A1)
REM Sleep Behavior Disorder
Initial management involves securing the environment to avoid injury and treating any underlying primary sleep disorder, such as RLS or SDB. Pharmacological treatment includes clonazepam and melatonin.[78] Melatonin is initiated at a 3 mg dose and increased in 3 mg increments until the behaviors subside. If no clinical response is achieved with the 18 mg nightly dose, it is replaced or augmented with clonazepam. (B3)
Obstructive Sleep Apnea
Patient education and behavior modification, such as controlling obesity, avoiding alcohol, and sedating medications, are recommended. An apnea-hypopnea index (AHI) >15 events/hour warrants positive airway pressure (PAP) therapy.[79] PAP therapy is also recommended for patients with mild OSA (AHI of 5 to 15) who have excessive daytime sleepiness.[80]
In certain Parkinson disease types that are advanced and associated with motor disability and upper airway dysfunction, the management of SDB may become more challenging. First, the ability of patients with Parkinson disease to tolerate continuous positive airway pressure (CPAP) and their ability to appropriately use the mask is usually more complicated due to the upper extremities motor disability; second, sleep disturbances in Parkinson disease are likely multifactorial and often associated with upper airway dysfunction due to the neurodegenerative processes. Third, patients with Parkinson disease may be less compliant with CPAP therapy than the general population and may discontinue the treatment. Factors that lead to the discontinuation of therapy are related to weakness and mobility impairment to the upper extremities, mask claustrophobia, increased awakenings, lack of education, and inconvenience.[81] Many of these factors can be alleviated by the use of the nasal interface and standardized CPAP education. Therefore, conventional therapies may not be fully accepted by these patients with many chronic issues, and individualized care is greatly needed.[82](A1)
The treatment of excessive daytime sleepiness associated with Parkinson disease or hypersomnia due to Parkinson disease, despite optimal treatment of SDB, is challenging and could be due to associated factors such as insufficient sleep or overlapping insomnia, the existence of adverse effects of drugs such as dopaminergic agents, the presence of narcolepsy or hypersomnia due to central origin, and concern of adverse effects from using stimulating alerting agents. Several open-label placebo-controlled studies, with relatively small sample sizes, investigated the use of modafinil in Parkinson disease-associated hypersomnia.[83][84] Research study results reported that the treatment with modafinil improved subjective sleepiness as measured by the Epworth Sleepiness Scale without major adverse effects. However, the objective assessment of sleepiness using maintenance of wakefulness test (MWT) or multiple sleep latency tests (MSLT) did not reveal significant improvement with modafinil.[83][85](A1)
Differential Diagnosis
Differential Diagnosis of Sleep Disorders in Parkinson Disease
Insomnia
- Circadian rhythm disorders such as delayed sleep-wake disorder and restless legs syndrome in patients with sleep onset difficulty
- Sleep apnea and periodic limb movement disorder in patients with sleep maintenance difficulty
- Advanced sleep-wake phase disorder and depression in patients with early morning awakening
Restless legs syndrome
- Muscle cramps and nocturnal motor symptoms from wearing off of dopaminergic medications from Parkinson disease
REM sleep behavior disorder
- Non-REM parasomnias
- Parasomnia overlap disorder
- Nightmares
- Obstructive sleep apnea
- Periodic limb movement disorder
- Sleep-related hypermotor epilepsy
Differential Diagnosis of Sleep Disorders in Alzheimer Disease
Circadian rhythm disorder
- Non-24-hour sleep-wake rhythm disorder
- Shift work disorder
- Jet lag disorder
Insomnia
- Short sleep duration
- Chronic sleep insufficiency
- Circadian rhythm sleep-wake disorders
- Restless legs syndrome
- Obstructive sleep apnea
- Psychiatric disorders such as depression and anxiety
Hypersomnia
- Insufficient sleep
- Obstructive sleep apnea
- Central sleep apnea
- Narcolepsy
Obstructive Sleep Apnea in both Parkinson and and Alzheimer Diseases
Excessive daytime sleepiness potentially caused by the following:
- Insufficient sleep
- Narcolepsy
- Circadian rhythm disorder
- Restless legs syndrome
- Periodic limb movement disorder
- Neurodegenerative diseases
- Medications
Prognosis
Patients with idiopathic REM sleep behavior disorder have shown a high risk of conversion to Parkinson disease and other synucleinopathies, with a 33% conversion rate at 5 years, 75.7% at 10 years, and 90.9% at 14 years.[37] Hence, patients with idiopathic RSBD need evaluation during their follow-up visits to look for early signs of disease with further diagnostic workup if needed. Patients with Parkinson disease and RSBD have more falls and are at a higher risk of developing dementia, hallucinations, and autonomic dysfunction. They have poorer treatment response and more widespread brain atrophy and hence lead to a greater disease burden compared to those without RSBD.[30][86]
In normal subjects, sleep deprivation has been linked to an increase in beta-amyloid levels, which can potentially cause Alzheimer disease later.[87] Sleep disturbances are common in patients with dementia and are speculated to be a risk factor for cognitive decline. A decreased percentage of REM sleep has been associated with an increased risk of dementia.[88] Sleep disorders are known to worsen with the worsening of the disease, and the intensification at the later stage of the disease is a predictive factor for mortality.[58]. The overall survival in a patient with Alzheimer disease is variable and depends on the extent of impairment, but in many cases, it is approximately 4 to 6 years.[89]
Complications
Addressing sleep disorders in patients with neurodegenerative diseases involves navigating the complications from treatment and from the lack of treatment. Each approach carries its own risks, significantly impacting the patient's overall health and quality of life.
Complications from Lack of Treatment
- Obstructive sleep apnea: early-onset dementia and neurodegeneration, cardiovascular complications such as hypertension, myocardial infarction, and cerebrovascular accident [90]
- Insomnia: hypertension, diabetes, depression, obesity, myocardial infarction, cerebrovascular accident
- REM sleep behavior disorder: injury to self or the sleeping partner, progression to synucleinopathies, and other neurodegenerative conditions
- Restless legs syndrome: insomnia, anxiety, depression
- Circadian rhythm disorder: delirium (in older patients with dementia), social discordance
Complications of Treatment
- Continuous positive airway pressure therapy: runny nose, dry mouth, nosebleeds, and skin irritation
- Melatonin: central nervous system depressant effects, hallucinations, and agitation
- Bright light therapy: headache, nausea, jitteriness
Deterrence and Patient Education
Patients with a diagnosis of Alzheimer disease or Parkinson disease need to be monitored for sleep disturbances. Symptoms such as restless sleep, difficulty sleeping, movements during sleep, and repetitive leg movements suggest possible sleep-related disorders and should prompt evaluation by a healthcare professional. Patients are best evaluated by obtaining a detailed history and asking pertinent questions. A sleep study is performed to diagnose certain disorders, such as sleep apnea.
The treatment of most sleep disorders focuses on conservative measures such as maintaining good sleep hygiene and behavior therapy, depending on the type of sleep disorder. Maintaining a regular sleep schedule, avoiding caffeine, tobacco, and alcohol in the evening, limiting exposure to light before bedtime, and not using the bed for purposes other than sleeping is recommended. If the diagnosis of sleep apnea is made, the patients are prescribed a breathing mask (eg, CPAP) that must be worn at night while sleeping. In some sleep disorders relating to the sleep cycle, interventions such as bright light therapy and physical activity may be advised. Medications such as melatonin may be prescribed in some situations. Untreated sleep disorders like sleep apnea are a major risk factor for high blood pressure, heart attack, and other serious cardiovascular problems. Prompt management of sleep disorders can possibly slow the progression of dementia and other related neurodegenerative diseases.
Pearls and Other Issues
Clinical pearls for managing sleep disorders in patients with neurodegenerative diseases offer valuable insights, and include the following:
- There remains a high prevalence of sleep disorders in patients with neurodegenerative conditions.
- Promptly recognizing and managing sleep disturbances can significantly impact overall patient outcomes and, in some cases, delay the progression of the neurodegenerative condition.
- Inadequate dopamine agonism in Parkinson disease can lead to insomnia, and excess agonism can lead to hypersomnia. A change in medication dosage is preferred if other causes are ruled out.
- Managing insomnia in Alzheimer disease can lead to a decreased rate of neurodegeneration.
- Idiopathic RLS has a higher rate of progression of Parkinson disease, and patients should be regularly monitored for those signs through periodic follow-up.
Enhancing Healthcare Team Outcomes
Sleep disorders are highly prevalent in patients with neurodegenerative disorders but may remain underrecognized and undertreated. Early identification and management are essential in improving patient care outcomes; this care necessitates a collaborative approach involving physicians, advanced practice providers, nurses, sleep technicians, psychiatrists, psychotherapists, and nursing home caregivers—among other healthcare professionals.
Essential clinical skills include proficiency in diagnosing and treating the primary neurodegenerative condition and associated sleep disturbances. Strategies involve employing evidence-based protocols for sleep evaluation and management tailored to individual patient needs, considering the complex interactions between neurological and sleep pathologies.
Effective interprofessional communication is vital for coordinating care plans, ensuring seamless transitions between healthcare settings, and facilitating shared decision-making. This collaboration enhances patient-centered care, improves outcomes by addressing holistic needs, promotes patient safety through comprehensive medication management and adverse event monitoring, and supports patient and caregiver education and support throughout the disease trajectory. By leveraging collective expertise and fostering collaborative practices, the interprofessional healthcare team can significantly enhance patient-centered care, improve outcomes, ensure patient safety, and optimize team performance in managing sleep and neurodegenerative disorders.
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