Rem Sleep Disorder: Dementia's Inevitable Precursor?

REM sleep behaviour disorder (RBD) is a sleep condition characterised by dream enactment and loss of REM atonia. Individuals with RBD often present with complaints of injury to themselves or their bed partner due to violent movements during sleep. RBD patients have a high risk of developing neurodegenerative diseases, with over 70% developing parkinsonism or dementia within 12 years of their diagnosis. However, it is unclear whether RBD is a causal factor in the development of neurodegenerative diseases or simply an early indicator.

RBD affects around 1% of the general population worldwide and about 2% of adults over 65. The disorder occurs during the rapid eye movement (REM) stage of sleep, which is often associated with dreaming. During REM sleep, your brain rhythms are similar to when you are awake, your muscles lose tone so you are unable to move, and your eyes, while closed, move quickly. However, someone with RBD will act out their dreams, with violent and aggressive dreams being reported by patients. These incidents often result in injuries, with 60% of patients and 20% of bed partners sustaining an injury during sleep.

RBD can occur at any age, but symptoms usually start in people in their 40s and 50s. For those younger than 40, antidepressants are the most common cause of RBD. In these younger patients, it affects biological males and females about equally, but past age 50, it’s more common in biological males.

The prognosis for RBD depends on the subtype. Patients diagnosed with RBD secondary to medication have the most promising prognosis, with the disorder often resolving once the medication is withdrawn. For patients with RBD presenting as part of a clinically defined neurodegenerative condition, such as Parkinson's disease, the management of their sleep disorder should form part of their holistic care. Finally, for patients diagnosed with apparently idiopathic disease, the prognosis remains uncertain.

What is REM sleep behaviour disorder?

REM sleep behaviour disorder (RBD) is a parasomnia involving dream enactment behaviour associated with a loss of muscle tone during rapid eye movement (REM) sleep. During normal REM sleep, the body experiences a loss of muscle tone (paralysis) which prevents the physical acting out of dreams. However, in RBD, this paralysis is incomplete or absent, allowing the person to act out their dreams.

RBD is characterised by vivid, intense, and violent dreams, with patients reporting that they are being chased or defending themselves. This results in behaviours such as talking, yelling, punching, kicking, jumping from bed, arm flailing, and grabbing. These dream-enacting behaviours can lead to injuries to the patient or their bed partner, with 60% of patients and 20% of bed partners sustaining injuries during sleep. RBD can occur at any age, but symptoms usually begin in a person's 40s and 50s. It is more common in men, particularly those over 50.

The exact cause of RBD is unknown, but it is often associated with degenerative neurological conditions such as Parkinson's disease, multisystem atrophy, and diffuse Lewy body dementia. RBD may precede these diseases or occur at any time during their progression. It is also linked to the use of certain antidepressants and sleep aids, such as SSRIs and sedative-hypnotics.

The diagnosis of RBD requires a combination of dream enactment behaviours, either reported by the patient or observed during a sleep study, and confirmation of REM sleep without atonia (loss of muscle tone) through polysomnography (PSG). Treatment focuses on reducing the risk of injury to the patient and their bed partner, as well as managing the underlying causes and symptoms.

What causes REM sleep behaviour disorder?

REM sleep behaviour disorder (RBD) can be divided into three categories: idiopathic RBD, drug-induced RBD, and secondary RBD due to a medical condition. Idiopathic RBD is most suggestive in neurodegenerative synucleinopathies, including dementia with Lewy bodies, Parkinson's disease, olivopontocerebellar degeneration, multiple-system atrophy, and Shy-Drager syndrome. The literature suggests that RBD is precipitated by aberrant connections between the brainstem control of muscle tonicity and the cortex.

Drug-induced RBD is common in individuals who are taking antidepressants. The most likely antidepressants that will incite an RBD episode are serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). Other acute transient forms of RBD involve toxic metabolic encephalopathy—most commonly involving ethanol use.

RBD with concomitant narcolepsy may be considered a distinct phenotype of RBD. It is characterised by less violent or complex behaviour during REM sleep, earlier age of onset, equal sex distribution, and hypocretin (orexin) deficiency.

RBD has also been associated with Wilson disease, cerebellar degeneration, and autoimmune encephalitis. Some studies suggested that secondary RBD due to paraneoplastic cerebellar degeneration could be immune-mediated, which improved after immunotherapy.

A novel association between antibodies (mainly IgG4) to a neuronal antigen against IgLON5 (a neuronal cell adhesion molecule) and RBD has been reported, suggesting a tauopathy. Neural histopathology studies in cases of autoimmune-mediated RBD showed neuronal loss and extensive deposits of hyperphosphorylated tau in the tegmentum of the brainstem and hypothalamus.

What are the links between the sleep disorder and dementia?

REM sleep behaviour disorder (RBD) is a parasomnia in which the normal paralysis of REM sleep is lost, causing patients to act out their dreams. It is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. It is observed in 25% to 58% of patients diagnosed with Parkinson's, 70% to 80% of patients with dementia with Lewy bodies and 90% to 100% of those with multiple system atrophy.

A study of 1,280 patients with RBD who didn't have parkinsonism or dementia found that after 12 years, 73.5% of those with RBD had developed a related neurodegenerative disorder. Some of the factors that independently increased the risk of developing a neurodegenerative disorder were the presence of irregular motor symptoms, abnormal dopamine levels, loss of sense of smell, cognitive impairment, abnormal colour vision, erectile dysfunction, constipation and older age.

The prognosis for RBD depends on the subtype. For patients with RBD presenting as part of a clinically-defined neurodegenerative condition, the presence of RBD marks a less favourable disease phenotype. In Parkinson's, for example, the presence of RBD is associated with a greater non-motor burden and a more adverse prognosis.

RBD may be the first symptom of Parkinson's disease or dementia with Lewy bodies. It is a readily-diagnosable but often-undetected early-stage neurodegenerative syndrome.

Does an early diagnosis help?

REM sleep behaviour disorder (RBD) is a condition that is a prodrome for neurodegenerative diseases, particularly α-synucleinopathies, which are characterised by an abnormal accumulation of aggregates of α-synuclein protein in the neurons or glia. Examples include Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy.

People with isolated REM sleep behaviour disorder have a high lifetime risk of developing a neurodegenerative disease, including dementia. However, the disclosure of this risk remains controversial due to the long latency to disease onset and the lack of preventative strategies.

An early diagnosis of dementia can help in several ways:

• It helps to get an accurate diagnosis and understand what to expect. Some treatable conditions can produce similar symptoms to dementia, such as vitamin deficiencies, thyroid disease, sleep disorders, alcohol abuse, or depression.
• It enables individuals to participate more actively in their healthcare decisions and future plans.
• It allows for more effective use of treatments, including medications and alternative therapies, which are typically most effective when started early.
• It provides an opportunity to set priorities and make empowering choices, such as deciding when to stop working, making legal and financial plans, and sharing wishes with family and friends.
• It allows individuals to take advantage of resources, such as support groups, and local Alzheimer Society information and education programs, to help them live well with dementia.
• It helps family members understand the disease and its progression, enabling them to provide better support.
• It empowers individuals to speak out, raise awareness, and advocate for quality care and increased funding for research.
• It provides an opportunity to participate in clinical trials and other research to improve diagnosis and enhance care.
• It helps to reduce the stigma associated with dementia by encouraging individuals to share their experiences and live life to the fullest.

How is REM sleep behaviour disorder treated?

REM sleep behaviour disorder (RBD) is a condition that is a prodrome for neurodegenerative disease, particularly α-synucleinopathies, which are characterised by an abnormal accumulation of aggregates of α-synuclein protein in the neurons or glia. While RBD is highly predictive of neuronal degeneration, there are currently no disease-modifying strategies to mitigate the risk of neurodegeneration. However, there are treatments available to reduce the frequency and severity of disruptive nocturnal behaviours and injuries, including safety strategies and medications.

Safety Strategies

• Removing breakable objects from the room
• Protecting windows
• Padding floors

Medications

• Melatonin
• Clonazepam

In addition to the above treatments, patients may also choose to participate in research. Proper treatment of the disease can help prevent injury and improve quality of life.

Frequently asked questions