Prodromal dementia with Lewy bodies in REM sleep behavior disorder: A multicenter study

Abstract

Introduction: Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia.

Methods: IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed-effect models determined the annual progression of neuropsychological testing.

Results: Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes.

Discussion: In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion.

Highlights: Cognitive decline in iRBD begins up to 10 years prior to phenoconversion. Attention and executive dysfunction are the strongest predictors of dementia in iRBD. Decline in episodic memory best distinguished dementia-first from parkinsonism-first phenoconversion.

Keywords: Parkinson's disease; REM sleep behavior disorder; dementia with Lewy bodies; evolution; pre-diagnostic; prodromal stage.

FIGURE 1

Neuropsychological testing in iRBD at baseline. (A) Pooled results for each neuropsychological test in all iRBD participants using a meta‐analysis of single means. Detailed results by study center are shown in Figure S1. (B) Mean testing results sub‐grouped by phenoconversion status. TMT, trail making test.

FIGURE 2

Cumulative incidence of dementia phenoconversion in iRBD stratified by impaired baseline testing (tests of attention and executive domains). Results are presented according to baseline neuropsychological test (impaired z‐score ≤ −1.5). Hazard ratios according to competitive risk regression are shown, adjusting for age, sex, education, depression, and study center, with 95% confidence intervals in parentheses. TMT, trail making test.

FIGURE 3

Cumulative incidence of dementia phenoconversion in iRBD stratified by impaired baseline testing (tests of memory, language, visuospatial domains, and MCI). Results are presented according to baseline neuropsychological test (impaired z‐score ≤ −1.5). Hazard ratios according to competitive risk regression are shown, adjusting for age, sex, education, depression, and study center, with 95% confidence intervals in parentheses. MCI, mild cognitive impairment.

FIGURE 4

Annual progression of neuropsychological testing in iRBD. Neuropsychological testing and assessed up to 10 years prior to phenoconversion or censoring. Individual dots represent each participant; solid lines represent estimated progression by linear mixed‐effect modeling; shaded areas represent 95% confidence intervals; horizontal dotted lines indicate thresholds for reduced cognitive performance (z‐score < zero) and impaired performance (z‐score ≤ −1.5). MMSE, Mini‐Mental State Examination; MoCA, Montreal Cognitive Assessment; TMT, Trail Making Test.