How Dreams Can Predict Neurodegenerative Disorders

For most of us, even when we’re having an incredibly realistic dream, we know that we’ll eventually wake up and find that we haven’t been running around or fighting off enemies. For around 1% of the global population, however, this is not the case (Haba-Rubio et al. 2017). REM behavior disorder (RBD) is characterized by people physically acting out their dreams during the rapid eye movement (REM) stage of sleep. This may sound harmless, comical even, but the reality can be dangerous for the person enacting their dreams as well as their bed partner.

A high proportion of RBD patients go on to develop neurodegenerative disorders: Parkinson’s disorder (PD), the neurodegenerative disorder characterized by tremors and stiffness, multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). The silver lining to this correlation is that RBD patients can ‘look out’ for their cognitive and motor decline and access treatment and interventions earlier than they might without the initial RBD diagnosis.

In this blog, we will discuss what RBD is, treatments for the condition, and what is thought to cause it. We will also look at the link between this rare sleep disorder and the onset of certain neurodegenerative disorders.

What Is RBD?

REM sleep is the stage of the sleep cycle where most dreaming happens. During REM sleep our brain activity is similar to when we are awake, but, crucially, skeletal muscles become temporarily paralyzed: stopping us from thrashing around in bed and injuring ourselves or others (Arrigoni et al. 2016). For people with RBD, there is dysfunction in the pathway involved in shutting off the use of skeletal muscles during REM sleep, meaning there is nothing to stop them from performing the actions that are happening in their dream.
RBD is a non-familial disorder, meaning susceptibility is likely to be dependent on both environmental and genetic factors. Studies of RBD genetics suggest that the disease is driven by single nucleotide polymorphisms (SNPs) in genes including SNCA, which encodes α-synuclein. Accumulation of this neuronal protein forms the protein aggregates, known as Lewy bodies, in DLB, and causes cognitive decline in PD, MSA, and DLB (Fernández-Santiago et al. 2017).  So, a mutation in SNCA seems to be driving both RBD and the onset of certain neurodegenerative disorders.

Males are reportedly much more likely to have RBD than women, but a look into the clinical cohorts used to research RBD shows that an unbalanced male to female ratio was commonly used (Olson et al. 2000). The small number of women included in the studies could mean the results are not representative of the actual population. In contrast, population-based studies, which aim to use whole populations of people rather than individuals involved in a study, have shown that both sexes are equally likely to have RBD (Haba-Rubio et al. 2018).

For some, acute RBD may be spurred by heightened emotional states or withdrawal from alcohol or sedatives. Dream enactment typically only lasts for around six months in these acute cases (Nielson et al. 2009). However, for others, RBD seems to begin spontaneously and without a cause and becomes a chronic problem — this type of chronic RBD is often referred to as idiopathic RBD. As well as reducing the risk of harming themselves or others by padding furniture in the bedroom and removing potentially dangerous objects from near the bed, RBD sufferers are often prescribed a low dose of clonazepam, a drug commonly used in panic disorders to calm abnormal activity in the brain, to stop their dream enactment. For RBD patients, clonazepam is thought to work by enhancing inhibitory processes within the brain, such as the processes controlling muscle use during REM sleep (Dokkedal-Silva et al. 2020).

So, what does RBD have to do with neurodegenerative disorders?

RBD as an Early Predictor of Neurodegenerative Disorders

In 1996, 10 years after RBD was first described in scientific literature, Schenck et al. reported that people with chronic RBD have a significantly increased risk of developing PD. Since then, studies have confirmed that RBD is a predictor of other disorders affecting the brain including MSA and DLB. In fact, it is now estimated that 90% of patients with idiopathic RBD will eventually develop one of these brain degeneration conditions (Iranzo et al. 2014). Research has shown that approximately 30-60% of PD patients have RBD as a symptom occurring after their PD diagnosis (Krohn et al. 2020).

As mentioned, PD, MSA, and DLB are all neurodegenerative diseases involving α-synuclein. Misfolding and aggregation of α-synuclein in the brain leads to progressive degradation. As the disease progresses, cognitive and motor functions often decline gradually, and symptoms can be missed for a long time before diagnosis. RBD is one of the most specific predictors of α-synuclein-mediated neurodegenerative disorders, meaning people who present to clinics with RBD are likely to have an early diagnosis if they do go on to develop a neurodegenerative disease (Barone and Henchcliffe 2018). Early detection of neurodegenerative diseases is important as patients can begin to make lifestyle changes earlier when their brain is healthier. Certain treatments have also been shown to be more effective when administered earlier.

An RBD diagnosis can help to distinguish between different types of dementia: dementia with Lewy bodies or Alzheimer’s disease. Both types of dementia affect behavior, awareness, and movement; the main difference is that memory loss tends to be a more prominent symptom in early Alzheimer's compared to early dementia with Lewy bodies. Typically, it is hard to delineate between these two dementias, especially in the early stages, even when using MRI brain scans. However, if a patient has a history of RBD, they are more likely to have dementia with Lewy bodies, as it has been shown that only 2-3% of patients who go on to develop Alzheimer’s have a history of RBD (Murray et al. 2013). Distinguishing between different types of dementia allows patients to have early access to the correct treatments and interventions, which can help people to live independently at home for longer and give them time to plan for their future.

In general, sleep disorders are poorly understood by doctors and RBD is no exception. However, RBD represents an opportunity for research scientists to discover more about the complex neural mechanisms of sleep and dreams, as well as the cause and progression of α-synuclein-mediated neurodegenerative disorders.