REM-Sleep Behavior Disorder Associated With Worse Cognition in Subsequent Parkinson Disease

Anette Schrag, MD, PhD

Recently published data using participants from the PREDICT-PD study showed that cognitive function is impaired in groups at higher risk of developing Parkinson disease (PD), especially those with REM-sleep behavior disorder (RBD).¹

In the trial, 208 participants from PREDICT-PD, as well as 25 participants with PSG-confirmed RBD, were seen in person and underwent brief cognitive testing using the Montreal Cognitive Assessment (MOCA). Led by senior investigator Anette Schrag, MD, PhD, professor of clinical neurosciences, UCL Queen Square Institute of Neurology, the study compared higher and lower risk patients, defined as being below the lowest and within the highest 15th percentiles of risk, respectively, and RBD vs all PREDICT-PD participants from the general population.

Prevalence of mild cognitive impairment (MCI) level 1, which requires impairment in a global test of cognitive function like MOCA, was identified across the entire cohort. MCI in PD was classified using Movement Disorder Society (MDS) guidelines. Participants with RBD additionally underwent comprehensive 5-domain neuropsychometry, allowing categorization of level 2 MCI. The battery included 12 individual tests with at least 2 in each cognitive domain. Performance on each cognitive task was corrected for age and education using published normative data to calculate z-scores in place of each test score.

For PREDICT-PD participants, 117 were considered lower risk and 91 were considered higher risk based off their MOCA percentile. For those with RBD, 15 had RBD with level 2 MCI and 10 were cognitively normal. All told, total MOCA scores were worse in the higher risk group compared with the lower risk group (P = .009) and in the RBD group compared with PREDICT-PD participants. Specifically, rates of MCI level 1 were 12.8% in the lower-risk, 21.9% in the higher-risk, and 64% in patients with RBD (lower risk vs higher risk, P = .12; RBD vs PREDICT-PD, P <.01).

After using Bonferroni correction for multiple comparisons, investigators continued to observe worse cognition in the RBD group across most cognitive sub-domains of the MOCA (all domains except naming, P ≤.001). Between lower and higher risk participants, only memory scores differed (P = .002). As 60% (15 of 25) of participants with RBD fulfilled level 2 diagnostic criteria, those with MCI were older, had poorer smell (UPSIT score) and increased motor disability, but on direct comparison none of these differences were significant.

When assessing the cognitive profiles of participants with level 2 cognitive impairment, all 15 patients had multidomain cognitive impairment. Specifically, 93%, 87%, 67%, 47%, and 13% of patients respectively, had impairments in attention, memory, executive function, visuospatial, and language. Among the 10 cognitively normal individuals, only attention and, subtly, memory were reduced, whereas those with MCI, scores across all domains were reduced, particularly attention, with relative preservation of language.

READ MORE: Cognitive Impairments in Activities of Daily Living Predict Conversion to Parkinson Disease Dementia

"On comprehensive neuropsychological testing, RBD patients were most affected in attention and more subtly memory, suggesting early involvement of these domains," Schrag et al wrote. "In RBD patients who already met the definition of MCI, particularly attention but also other domains including visuospatial function and executive function domains were affected. This may suggest that visuospatial and executive functions deteriorate later in the course of the disease."

This was the first study to quantify rates of cognitive impairment using the MDS MCI criteria in different at-risk groups; however, there were limitations to the results. For example, the investigators noted that it is not known whether all at-risk participants will develop future PD, and how many of the patients with RBD will convert to PD. Additionally, RBD symptoms are unlikely to be reported at diagnosis but may be found on polysomnography; however, the prevalence rate for full ISCD-2 diagnosis of RBD is low, therefore this group may represent a small number of future patients with PD with RBD.

"RBD may represent a specific pathway to PD, with high levels of cognitive impairment and a specific cognitive profile," the study authors wrote. "Further work is needed to define rates of level II MCI in pre-diagnostic cohorts without RBD (for example, our higher risk cohort) and to longitudinally follow up all cohorts to define the specific tests most predictive of neurodegenerative disease in all pre-diagnostic patients."

REFERENCE
1. Nagy AV, Leschziner G, Eriksson SH, Lees A, Noyce AJ, Schrag A. Cognitive impairment in REM-sleep behavior disorder and individuals at risk of Parkinson’s disease. Parkinsonism Relat Disord. Published online January 31, 2023. doi:10.1016/j.parkreldis.2023.105312