Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease.
ABSTRACT Rapid eye movement sleep behavior disorder (RBD) is common in Parkinson disease (PD), but its relationship to the varied neurotransmitter deficits of PD and prognostic significance remain incompletely understood. RBD and cholinergic system degeneration are identified independently as risk factors for cognitive impairment in PD. We aimed to assess the association between cholinergic denervation and symptoms of RBD in PD patients without dementia.
Eighty subjects with PD without dementia (age, 64.6 ± 7.0 years; range, 50-82 years; 60 males, 20 females; mean Montreal Cognitive Assessment Test [MoCA] score, 26.2 ± 2.1; range 21-30) underwent clinical assessment, neuropsychological testing, and [(11)C]methylpiperidyl propionate acetylcholinesterase and [(11)C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 positron emission tomography (PET) imaging. (11)C3-Amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile (DASB) serotonin transporter PET imaging was performed in a subset of 35 subjects. The presence of RBD symptoms was determined using the Mayo Sleep Questionnaire.
Twenty-seven of 80 subjects (33.8%) indicated a history of RBD symptoms. Subjects with and without RBD symptoms showed no significant differences in age, motor disease duration, MoCA, Unified Parkinson Disease Rating Scale motor scores, or striatal DTBZ binding. Subjects with RBD symptoms, in comparison to those without, exhibited decreased neocortical, limbic cortical, and thalamic cholinergic innervation (0.0213 ± 0.0018 vs 0.0236 ± 0.0022, t = 4.55, p < 0.0001; 0.0388 ± 0.0029 vs 0.0423 ± 0.0058, t = 2.85, p = 0.0056; 0.0388 ± 0.0025 vs 0.0427 ± 0.0042, t = 4.49, p < 0.0001, respectively). Brainstem and striatal DASB binding showed no significant differences between groups.
The presence of RBD symptoms in PD is associated with relative neocortical, limbic cortical, and thalamic cholinergic denervation although not with differential serotoninergic or nigrostriatal dopaminergic denervation. The presence of RBD symptoms may signal cholinergic system degeneration.
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ABSTRACT: Over the past three decades, neuroimaging studies-including structural, functional and molecular modalities-have provided invaluable insights into the mechanisms underlying Parkinson disease (PD). Observations from multimodal neuroimaging techniques have indicated changes in brain structure and metabolic activity, and an array of neurochemical changes that affect receptor sites and neurotransmitter systems. Characterization of the neurobiological alterations that lead to phenotypic heterogeneity in patients with PD has considerably aided the in vivo investigation of aetiology and pathophysiology, and the identification of novel targets for pharmacological or surgical treatments, including cell therapy. Although PD is now considered to be very complex, no neuroimaging modalities are specifically recommended for routine use in clinical practice. However, conventional MRI and dopamine transporter imaging are commonly used as adjuvant tools in the differential diagnosis between PD and nondegenerative causes of parkinsonism. First-line neuroimaging tools that could have an impact on patient prognosis and treatment strategies remain elusive. This Review discusses the lessons learnt from decades of neuroimaging research in PD, and the promising new approaches with potential applicability to clinical practice.Nature Reviews Neurology 11/2014; 10(12). DOI:10.1038/nrneurol.2014.205 · 14.10 Impact Factor
Aktuelle Neurologie 10/2013; 40(08):452-461. DOI:10.1055/s-0033-1355379 · 0.32 Impact Factor
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ABSTRACT: Background Cholinergic projection systems degeneration is associated with dopamine nonresponsive features of Parkinson's disease (PD). Cholinergic deficits are variable in nondemented PD. Identification of cholinergic deficits in PD may help with selection of suitable patients for targeted cholinergic drug treatment in PD. The objective of this retrospective multivariate predictor analysis study was to identify clinical markers indicative of cholinergic deficits in PD patients, as assessed by acetylcholinesterase ([11C]PMP) positron emission tomography.Methods One hundred thirty-seven PD patients (34 female) participated; median modified Hoehn and Yahr score was 2.5 (range, 1-4), average age 65.6 ± 7.4 years, and average duration of motor disease symptoms of 6.0 ± 4.2 years. Subjects were dichotomized as “normocholinergic” or “hypocholinergic” based on a 5th percentile cutoff from normal for the basal forebrain-cortical and pedunculopontine nucleus-thalamic cholinergic projection systems. Previously identified clinical indices of cholinergic denervation were used for statistical prediction of cholinergic deficits. Logistic regression determined which risk factors predicted cholinergic deficits. Sensitivity, specificity, and accuracy were determined for the (combinations of) significant predictor variables.ResultsForty-nine (35.8%) hypocholinergic PD subjects were identified. The combination of rapid eye movement (REM) sleep behavior disorder (RBD) symptoms and fall history showed highest diagnostic accuracy (81.1%) for predicting combined thalamic and cortical cholinergic deficits. A combined assessment of 8.5 m walk time and lower score on the Montreal cognitive assessment scale provided diagnostic accuracy of 80.7% for predicting isolated cortical cholinergic denervation.Conclusion Assessment of clinical indices of cholinergic denervation may be useful for identifying suitable subjects for trials of targeted cholinergic drug treatments in PD. © 2014 International Parkinson and Movement Disorder SocietyMovement Disorders 02/2015; 30(2). DOI:10.1002/mds.26061 · 5.63 Impact Factor