Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies

Abstract

ObjectiveReview the effect of orthostatic hypotension (OH) and rapid-eye-movement sleep behavioural disorder (RBD) on survival, cognitive impairment and postural stability, and discuss pathogenic mechanisms involved in the association of these two common non-motor features with relevant clinical outcomes in α-synucleinopathies.MethodsWe searched PubMed (January 2007–February 2019) for human studies of OH and RBD evaluating cognitive impairment, postural instability, and survival in Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and pure autonomic failure (PAF). Included studies were analysed for design, key results and limitations as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.ResultsOH and RBD showed a positive association with cognitive impairment in PD and DLB, conflicting association in PAF, and no association in MSA. OH was correlated with incident falls and postural instability in PD and DLB but not in MSA. The association between RBD and postural instability was inconclusive; positive in five studies, negative in seven. OH, but not RBD, correlated with reduced survival in PD, DLB and MSA. The combination of OH and RBD was associated with cognitive impairment and more rapid progression of postural instability.ConclusionsOH and RBD yielded individual and combined negative effects on disability in α-synucleinopathies, reflecting a ‘malignant’ phenotype of PD with early cognitive impairment and postural instability. Underlying mechanisms may include involvement of selected brainstem cholinergic and noradrenergic nuclei.

Rivastigmine in Parkinson's Disease Dementia with Orthostatic Hypotension

“…19 This analysis, however, suggests that the different magnitude of benefit to rivastigmine in these populations may be at least in part accounted for by the relative differences in OH prevalence: higher in PDD compared to AD. 20 Furthermore, the presence of OH as a prominent marker of a "malignant" disease phenotype 20 may also explain prior analyses demonstrating a significantly greater response to rivastigmine among patients with more rapid disease progression. 21 An intriguing finding was the significantly larger cognitive benefit in patients with OH+ versus OHpatients for the capsule compared to the patch formulation at 76 weeks.…”

Parkinson's Disease: Glucocerebrosidase 1 Mutation Severity Is Associated with CSF Alpha‐Synuclein Profiles

“…This is of interest as RBD is specifically associated with alpha‐synucleinopathies and the GBA1 mutation carriers of the RBD cohort had a 3.2‐fold higher phenoconversion rate from RBD to parkinsonism and/or dementia than non‐ GBA1 carriers . Moreover, a recent review reported RBD to be positively associated with a more severe “malignant” phenotype, including cognitive impairment in PD and DLB . With more evidence arising, PD GBA seem to be a model for a malignant phenotype in PD.…”

“…12 Moreover, a recent review reported RBD to be positively associated with a more severe "malignant" phenotype, including cognitive impairment in PD and DLB. 13 With more evidence arising, PD GBA seem to be a model for a malignant phenotype in PD.…”

Sleep Disturbances and Sleep Disordered Breathing Impair Cognitive Performance in Parkinson’s Disease

“…RBD in PD patients and the akinetic PD subtype were found to be associated with impaired cognitive function in many studies ( Svenningsson et al, 2012 ; Jozwiak et al, 2017 ; Pilotto et al, 2019 ). Accordingly, overall cognitive performance particularly affecting visuospatial function, executive function, attention, and memory in PD patients with RBD compared to those without was demonstrated ( Huang et al, 2018 ).…”