Junior Award - Clinical Research
Prodromal dementia with Lewy bodies in REM sleep behavior disorder: A multicenter study  

Detecting and analyzing the early cognitive changes in RBD that can predict the development of further disease. 

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REM sleep behavior disorder (RBD) is a parasomnia that in most cases is related to an underlying neurodegenerative synucleinopathy. It is therefore a powerful predictor of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and in a minority of cases, multiple system atrophy (MSA). As such, RBD likely represents a prodromal stage of disease, and critically, may be the time when neuroprotective therapies are most likely to be effective.1  

Interestingly, those with RBD are at approximately equal risk developing either PD or DLB – however, determining which disease a patient will develop is difficult to predict. For example, our previous IRBDSG multicenter study examined the longitudinal progression of a number of clinical markers in RBD, and found that the only robust clinical marker that differentiated between those destined to develop PD versus those destined to develop DLB was cognitive dysfunction itself.2 We therefore set out to determine: 1) how early can we detect cognitive changes in RBD; and 2) which tests best predicted the development of dementia. 

We did this by following a group of 754 individuals with RBD and examining changes in comprehensive cognitive testing over time.3 The key findings were that baseline cognitive changes can be detected up to 10 years prior to the development of PD or DLB, particularly when using tests that assess attention and executive dysfunction. By contrast, when followed longitudinally, cognitive tests in the memory or visuospatial domains best distinguish between PD and DLB. 

These findings impact how we counsel our patients with RBD, since the early identification of those at risk of dementia allows us and our patients to anticipate and plan for the consequences of progressive cognitive decline. Moreover, these cognitive tests are relatively simple to administer and can be performed in the clinic or in low-resource settings. Finally, it highlights the importance of carefully following our RBD patients, since subtle changes in cognitive function can have significant downstream effects over time. 

References 

1. Postuma RB. Neuroprotective Trials in REM Sleep Behavior Disorder. Neurology. 2022;99:19–25.  
2. Joza S, Hu MT, Jung K-Y, et al. Progression of clinical markers in prodromal Parkinson’s disease and dementia with Lewy bodies: a multicentre study. Brain. Epub 2023 Mar 7.:awad072.  
3. Joza S, Hu MT, Jung K-Y, et al. Prodromal dementia with Lewy bodies in REM sleep behavior disorder: A multicenter study. Alzheimer’s & Dementia [online serial]. John Wiley & Sons, Ltd; 2023;n/a. Accessed at: https://alz.journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13386. Accessed July 31, 2023. 

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