TY - JOUR
T1 - Wake and non-rapid eye movement sleep dysfunction is associated with colonic neuropathology in Parkinson’s disease
AU - Sadoc, Mathilde
AU - Clairembault, Thomas
AU - Coron, Emmanuel
AU - Berthomier, Christian
AU - Dily, Séverine Le
AU - Vavasseur, Fabienne
AU - Pavageau, Albane
AU - St. Louis, Erik K.
AU - Péréon, Yann
AU - Neunlist, Michel
AU - Derkinderen, Pascal
AU - Leclair-Visonneau, Laurène
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Study Objectives: The body-first Parkinson’s disease (PD) hypothesis suggests initial gut Lewy body pathology initially propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels, a disease course presumed to likely occur in PD with rapid eye movement sleep behavior disorder (RBD). We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by nonrapid eye movement (NREM) sleep and wakefulness polysomnographic markers. Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining. We performed a visual semi-quantitative analysis of NREM sleep and wake electroencephalography (EEG), confirmed it with automated quantification of spindle and slow wave features of NREM sleep, and the wake dominant frequency, and then determined probable Arizona PD stage classifications based on sleep and wake EEG features. Results: The visual analysis aligned with the automated quantified spindle characteristics and the wake dominant frequency. Altered NREM sleep and wake parameters correlated with markers of PD severity, colonic PASH, and RBD diagnosis. Colonic PASH frequency also increased in parallel to probable Arizona PD stage classifications. Conclusions: Colonic PASH is strongly associated with widespread brain sleep and wake dysfunction, suggesting an extensive diffusion of the pathologic process in PD. Visual and automated analyses of polysomnography signals provide useful markers to gauge covert brain dysfunction in PD.
AB - Study Objectives: The body-first Parkinson’s disease (PD) hypothesis suggests initial gut Lewy body pathology initially propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels, a disease course presumed to likely occur in PD with rapid eye movement sleep behavior disorder (RBD). We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by nonrapid eye movement (NREM) sleep and wakefulness polysomnographic markers. Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining. We performed a visual semi-quantitative analysis of NREM sleep and wake electroencephalography (EEG), confirmed it with automated quantification of spindle and slow wave features of NREM sleep, and the wake dominant frequency, and then determined probable Arizona PD stage classifications based on sleep and wake EEG features. Results: The visual analysis aligned with the automated quantified spindle characteristics and the wake dominant frequency. Altered NREM sleep and wake parameters correlated with markers of PD severity, colonic PASH, and RBD diagnosis. Colonic PASH frequency also increased in parallel to probable Arizona PD stage classifications. Conclusions: Colonic PASH is strongly associated with widespread brain sleep and wake dysfunction, suggesting an extensive diffusion of the pathologic process in PD. Visual and automated analyses of polysomnography signals provide useful markers to gauge covert brain dysfunction in PD.
KW - Parkinson’s disease
KW - REM sleep behavior disorder
KW - colonic synucleinopathy
KW - slow waves
KW - spindles
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U2 - 10.1093/sleep/zsad310
DO - 10.1093/sleep/zsad310
M3 - Article
C2 - 38156524
AN - SCOPUS:85187545325
SN - 0161-8105
VL - 47
JO - Sleep
JF - Sleep
IS - 3
M1 - zsad310
ER -