Impaired Rem Sleep: Understanding Alzheimer's Impact

REM sleep behaviour disorder (RBD) is a parasomnia characterised by the loss of muscle atonia during REM sleep, which is usually present to prevent complex movements during dreams. RBD can occur in isolation or in association with a neurodegenerative disorder, such as Parkinson's disease, Lewy body dementia, or multiple system atrophy.

RBD is a strong predictor of neurodegeneration, particularly in synucleinopathies, which are characterised by an abnormal accumulation of aggregates of α-synuclein protein in neurons or glia. RBD is observed in 25-58% of patients with Parkinson's disease, 70-80% of patients with Lewy body dementia, and 90-100% of those with multiple system atrophy.

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

REM sleep behaviour disorder (RBD) and Alzheimer's disease

REM sleep behaviour disorder (RBD) is a sleep disorder characterised by the loss of muscle paralysis during the REM stage of sleep, which is when people tend to have vivid dreams. This can result in people with RBD physically and/or vocally acting out their dreams, often violently, and injuring themselves or their bed partner. RBD can occur with or without other neurological conditions. It is strongly associated with certain neurodegenerative disorders, such as Parkinson's disease, Lewy body dementia, and multiple system atrophy.

While Alzheimer's disease (AD) is reported as a possible development in patients with RBD, it is seen in a limited number of cases. Longitudinal studies have reported the development of AD in RBD patients in about 7% of cases, with variability ranging from 3% to 11%. However, the majority of longitudinal investigations do not report AD as a possible development for RBD patients, so this figure may be overestimated. The study of the relationship between RBD and AD is complicated by the overlap between the clinical features and neuropathology of the two conditions, as well as the use of clinical criteria alone in diagnosis.

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

RBD and dementia

REM sleep behaviour disorder (RBD) is a parasomnia, characterised by abnormal dream-enacting behaviour during the rapid eye movement (REM) sleep stage. RBD is either idiopathic or secondary to other neurological disorders and medications.

RBD is a core clinical feature of dementia with Lewy bodies (DLB) and may occur either in advance or simultaneously with the onset of DLB. The association between RBD and DLB is widely studied, with evidence suggesting that both are caused by the shared underlying synucleinopathy.

RBD is a strong predictor of neurodegeneration, particularly synucleinopathies such as Parkinson's disease, Lewy body dementia, and multiple system atrophy. However, longitudinal studies report that a minority of patients develop either overlapping forms of dementia or Alzheimer's disease.

Neuropsychological impairments identified in cross-sectional studies of RBD patients describe a profile similar to that observed in dementia related to synucleinopathies. However, only deficits in executive function predict the development of neurodegeneration. Longitudinal studies reported the development of Alzheimer's disease in RBD patients in about 7% of cases, with variability ranging from 3% to 11%.

RBD and the risk of developing 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 strong predictor of neurodegeneration, particularly synucleinopathies such as Parkinson's disease, Lewy body dementia, and multiple system atrophy. People with isolated REM sleep behaviour disorder (iRBD) have a high lifetime risk of developing a neurodegenerative disease, including dementia, but the disclosure of this risk remains controversial.

Neurodegeneration risk disclosure in iRBD is controversial due to a long latency to disease onset and a lack of preventative strategies. Balancing the ethical principles of beneficence, nonmaleficence, and autonomy is challenging. There are few data on disclosure in iRBD, but evidence from discussing risk in other diseases with dementia provides some guidance.

Several factors are linked to a prodromal state and can improve the prediction of neurodegeneration. These include symptomatic orthostatic hypotension, olfactory dysfunction, erectile dysfunction, hypersomnia, constipation, urinary dysfunction, cognitive dysfunction, history of depression, diabetes, physical inactivity, and severity of REM sleep without atonia. Neuroimaging findings with predictive value include abnormal presynaptic tracer uptake on dopamine transporter SPECT or PET imaging and hyperechogenicity on ultrasound of the substantia nigra.

Treatments are available to reduce the frequency and severity of disruptive nocturnal behaviours and injuries, including safety strategies and medications such as melatonin and clonazepam. However, there are currently no available strategies to mitigate the risk of neurodegeneration.

RBD and Alzheimer's disease diagnosis

REM sleep behaviour disorder (RBD) is a parasomnia characterised by the loss of the typical muscular atonia present during healthy REM sleep. It can occur in the absence of other neurological conditions or in association with a neurodegenerative disorder. RBD is a strong predictor of neurodegeneration, particularly synucleinopathies, such as Parkinson's disease, Lewy body dementia (LBD), or multiple system atrophy.

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

There is a high long-term rate of phenoconversion to neurodegenerative disease. Two large cohorts showed that among people with a mean age of 62 years, the median latency from onset of RBD to the diagnosis of neurodegenerative disease was 11 years. The majority (78-82.5%) of the patients in these cohorts were male, which may limit prediction in women. About 94% of RBD patients who develop neurodegenerative disease have an α-synucleinopathy, with LBD being the most common pathologic diagnosis.

Several other factors are also linked to a prodromal state and can improve the prediction of neurodegeneration. These include symptomatic orthostatic hypotension, olfactory dysfunction, erectile dysfunction, hypersomnia, constipation, urinary dysfunction, cognitive dysfunction, history of depression, diabetes, physical inactivity, and severity of RSWA. Treatments are available to reduce the frequency and severity of disruptive nocturnal behaviours and injury, including safety strategies and medications such as melatonin and clonazepam. However, there are no available strategies to mitigate the risk of neurodegeneration.

RBD treatment and Alzheimer's disease

REM sleep behaviour disorder (RBD) is a parasomnia, with abnormal dream-enacting behaviour during the rapid eye movement (REM) sleep. It is either idiopathic or secondary to other neurologic disorders and medications. RBD is a strong predictor of neurodegeneration, in particular synucleinopathies, such as Parkinson's disease, Lewy body dementia (LBD) or multiple system atrophy. People with isolated REM sleep behaviour disorder (iRBD) have a high lifetime risk of developing a neurodegenerative disease, including dementia, but the disclosure of this risk remains controversial.

The treatment of RBD should be applied carefully because around 33% to 65% of RBD patients have sleep-related injuries that are caused by the patients themselves. Modifying the sleep environment is necessary for RBD patients to prevent sleep-related injuries. Under certain circumstances, separating bedrooms may be necessary to prevent bed partners from getting injured. Pharmacologic therapy includes clonazepam and melatonin. Both are modestly effective in preventing sleep-related injuries.

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