Isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a strong predictor of Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, with more than 80% of cases ultimately converting to one of these synucleinopathies or another neurodegenerative disease.1 Therefore, studying the cognition of patients with iRBD may provide useful information about which aspects of cognition are the strongest predictors of phenoconversion, allowing physicians and patients to create better care plans and helping to identify appropriate patient populations for clinical trials.

To determine which aspects of cognition were most likely to predict dementia, researchers analyzed data from multiple centers of the International RBD Study Group. Performance on various cognitive tests, including the Trail Making Test (TMT), word list recognition and immediate recall, digit span, figure copy, and Stroop interference were measured. Baseline cognitive testing was set as the study baseline and patients were followed until phenoconversion. Researchers measured the time to dementia-first or parkinsonism-first phenoconversion.

The study, published in Alzheimer’s & Dementia, included 754 participants with polysomnogram-confirmed iRBD. The average age at baseline testing was 67.4 and the average follow-up time was 3.3 years. Dementia-first phenoconverters were significantly older and more likely to have baseline mild cognitive impairment than parkinsonism-first converters and non-converters.

“When stratifying baseline scores by phenoconversion status, a general trend of reduced cognitive performance was observed in dementia-first phenoconverters relative to parkinsonism-first and unconverted participants. This was most clear in tasks of attention, executive function, and learning/memory,” observed the study authors.

The strongest predictors of dementia (hazard ratio [HR] > 3 in dementia phenoconverters vs parkinsonism phenoconverters) included any impaired attention test, Stroop interference, any impaired executive domain test, trial making tests (TMT A, TMT B, TMT B A), Semantic fluency, any impaired memory test, and Word list immediate recall.

Dementia-first phenoconverters showed abnormal TMT-A and TMT-B scores up to 10 years before dementia, and a broad decline in various cognitive domains over time, whereas parkinsonism-first and non-converters demonstrated a more modest decline and small improvements in a few measures.

The study supports the idea that early cognitive testing in patients with iRBD may allow for the identification of patients who are likely to develop dementia, information that may be used to identify individuals for participation in clinical trials or to implement interventions that are more effective in the early stages of neurodegeneration.

Read the study

References:

1. Postuma RB, Iranzo A, Hu M, et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019; 142: 744-759. doi:10.1093/BRAIN/AWZ030