Approved Research

Defining a signature of prodromal Parkinson's disease in the UK Biobank cohort

Lay summary

We currently have no cure or treatments that slow down disease progression in Parkinson's disease (PD), which will double in prevalence in the next 25 years, affecting >10 million people worldwide. This relentlessly progressive condition has devastating consequences for individuals and families, being a leading global cause of movement-related disability and dementia.

There is compelling evidence for a causal relationship between sleep disturbance and disorders such as PD and dementia. However, it isn't clear how one causes the other. Medical interventions can normalize sleep and may therefore represent a novel strategy to slow down disease progression or delay the onset of Parkinson's (PD). It is therefore critical to determine how sleep problems may accelerate neuronal death and its underlying biological pathways.

Patients with a disorder called REM-sleep behaviour disorder (RBD) represent an emerging group at high risk of future PD. These individuals suffer a sleep disorder occurring in the dream phase of sleep, the rapid eye movement (REM) phase. Subjects with so called REM-sleep behaviour disorder (RBD) wake their bed partners during violent and vivid dreams, which they enact through movement and vocalization, e.g. kicking their bedpartner. The Gold-standard diagnosis of RBD is usually made using a technique called polysomnography (PSG), recording bodily functions including brain activity, eye movements, muscle activity, heart rhythm, blood pressure, and body movement during sleep.

Research studies have shown that 6 % of RBD patients convert to PD each year or a related neurodegenerative condition e.g., dementia. In addition, PD patients with symptoms of RBD manifest higher rates of dementia, cognitive, and motor symptom progression.

RBD patient cohorts therefore represent an extraordinary opportunity to capture the

early molecular/cellular mechanisms preceding the onset of PD symptoms, evident

only after >50% of dopaminergic neurons in the brain have been lost. However, so far, no molecular or cellular mechanism has been identified explaining how an individual converts from the sleep disorder RBD to the neurodegenerative disorder PD.

Our research aims at studying those RBD patients who have not yet developed PD, so that we can capture and characterise the clinical symptoms and underlying mechanisms driving future PD risk. We aim to compare findings from the Discovery sleep-clinic cohort of RBD patients with those from UK Biobank, so we know how common RBD is in the general population and its effect on future PD risk.