Glymphatic dysfunction potentially contributes to Parkinson's disease (PD) via impaired clearance of metabolic waste products. Obstructive sleep apnea (OSA) can disturb sleep, which is necessary for proper glymphatic function, and is frequent in PD. We investigated the glymphatic function in de novo PD and its relation to OSA. Fifty-four PD patients (mean age 58.9 ± 12.2 years) and 32 controls (mean age 59.4 ± 8.3 years) underwent polysomnography and 3 T magnetic resonance imaging of the brain. Diffusion tensor imaging along the perivascular space (DTI-ALPS) was calculated using atlas-based automatic regions of interest selection. In PD, ALPS-index negatively correlated with apnea-hypopnea index (rho = -0.41; p = 0.002), oxygen desaturation index (rho = -0.38; p = 0.006), sleep stage N1 (rho = -0.42; p = 0.002), and arousal index (rho = -0.24; p = 0.018), while in controls, no such correlations were observed. Glymphatic dysfunction is related to OSA severity in de novo PD but not in controls. We suggest that OSA may contribute to neurodegeneration via glymphatic impairment in PD.

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czechia

Department of Radiology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czechia

Faculty of Biomedical Engineering Czech Technical University Prague Kladno Czechia

Radiodiagnostic Department Na Homolce Hospital Prague Czechia

See more in PubMed

Iliff, J. J. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. PubMed PMC

Rasmussen, M. K., Mestre, H. & Nedergaard, M. The glymphatic pathway in neurological disorders. PubMed PMC

Kress, B. T. et al. Impairment of paravascular clearance pathways in the aging brain. PubMed PMC

Tarasoff-Conway, J. M. et al. Clearance systems in the brain-implications for Alzheimer disease. PubMed PMC

Verheggen, I. C. M., Van Boxtel, M. P. J., Verhey, F. R. J., Jansen, J. F. A. & Backes, W. H. Interaction between blood-brain barrier and glymphatic system in solute clearance. PubMed

Natale, G. et al. Glymphatic system as a gateway to connect neurodegeneration from periphery to CNS. PubMed PMC

Plog, B. A. & Nedergaard, M. The glymphatic system in central nervous system health and disease: past, present, and future. PubMed PMC

Lin, L. et al. Impaired glymphatic system in secondary degeneration areas after ischemic stroke in rats. PubMed

Plog, B. A. et al. Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system. PubMed PMC

Sundaram, S. et al. Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease. PubMed PMC

Reeves, B. C. et al. Glymphatic system impairment in Alzheimer’s disease and idiopathic normal pressure hydrocephalus. PubMed PMC

Tomizawa, Y. et al. The glymphatic system as a potential biomarker and therapeutic target in secondary progressive multiple sclerosis. PubMed

Nepozitek, J., Dusek, P. & Sonka, K. Glymphatic system, sleep, and Parkinson’s disease: interconnections, research opportunities, and potential for disease modification. PubMed PMC

Jessen, N. A., Munk, A. S., Lundgaard, I. & Nedergaard, M. The glymphatic system: a beginner’s guide. PubMed PMC

Chong, P. L. H., Garic, D., Shen, M. D., Lundgaard, I. & Schwichtenberg, A. J. Sleep, cerebrospinal fluid, and the glymphatic system: a systematic review. PubMed PMC

Xie, L. et al. Sleep drives metabolite clearance from the adult brain. PubMed PMC

Nedergaard, M. & Goldman, S. A. Glymphatic failure as a final common pathway to dementia. PubMed PMC

Hablitz, L. M. et al. Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. PubMed PMC

Lee, H. J., Lee, D. A., Shin, K. J. & Park, K. M. Glymphatic system dysfunction in obstructive sleep apnea evidenced by DTI-ALPS. PubMed

Yu, Q. et al. Obstructive sleep apnea in Parkinson’s disease: a prevalent, clinically relevant and treatable feature. PubMed

Scott-Massey, A. et al. Glymphatic system dysfunction and sleep disturbance may contribute to the pathogenesis and progression of Parkinson’s disease. PubMed PMC

Meinhold, L. et al. T2 MRI visible perivascular spaces in Parkinson’s disease: clinical significance and association with polysomnography measured sleep. PubMed PMC

Schreiner, S. J. et al. Slow-wave sleep and motor progression in Parkinson disease. PubMed

Gesi, M. et al. The role of the locus coeruleus in the development of Parkinson’s disease. PubMed

Hauglund, N. L. et al. Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep. PubMed

Cui, H. et al. Decreased AQP4 expression aggravates ɑ-synuclein pathology in parkinson’s disease mice, possibly via impaired glymphatic clearance. PubMed

Jiang, Q. MRI and glymphatic system. PubMed PMC

Iliff, J. J. et al. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. PubMed PMC

de Leon, M. J. et al. Cerebrospinal fluid clearance in alzheimer disease measured with dynamic PET. PubMed PMC

Pizzo, M. E. et al. Intrathecal antibody distribution in the rat brain: surface diffusion, perivascular transport and osmotic enhancement of delivery. PubMed PMC

Taoka, T. et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases. PubMed

Taoka, T. et al. Diffusion tensor image analysis along the perivascular space (DTI-ALPS): revisiting the meaning and significance of the method. PubMed PMC

Gouveia-Freitas, K. & Bastos-Leite, A. J. Perivascular spaces and brain waste clearance systems: relevance for neurodegenerative and cerebrovascular pathology. PubMed PMC

Ringstad, G. Glymphatic imaging: a critical look at the DTI-ALPS index. PubMed

Marecek, S. et al. Exploring glymphatic system alterations in iRBD and Parkinson’s disease using automated DTI-ALPS analysis. PubMed PMC

Jiang, D. et al. Regional glymphatic abnormality in behavioral variant frontotemporal dementia. PubMed PMC

Hsiao, W. C. et al. Association of cognition and brain reserve in aging and glymphatic function using diffusion tensor image-along the perivascular space (DTI-ALPS). PubMed

Wei, Y. C. et al. Vascular risk factors and astrocytic marker for the glymphatic system activity. PubMed PMC

Malhotra, A., Mesarwi, O., Pepin, J. L. & Owens, R. L. Endotypes and phenotypes in obstructive sleep apnea. PubMed PMC

Cai, G. E. et al. Sleep fragmentation as an important clinical characteristic of sleep disorders in Parkinson’s disease: a preliminary study. PubMed PMC

Norlinah, M. I. et al. Sleep disturbances in Malaysian patients with Parkinson’s disease using polysomnography and PDSS. PubMed

Yaffe, K. et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. PubMed PMC

Jackson, M. L., Howard, M. E. & Barnes, M. Cognition and daytime functioning in sleep-related breathing disorders. PubMed

Tian, S. et al. Association between body mass index and glymphatic function using diffusion tensor image-along the perivascular space (DTI-ALPS) in patients with Parkinson’s disease. PubMed PMC

Newman, A. B. et al. Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study. PubMed

Bae, Y. J. et al. Glymphatic function assessment in Parkinson’s disease using diffusion tensor image analysis along the perivascular space. PubMed

Benveniste, H. et al. The glymphatic system and waste clearance with brain aging: a review. PubMed PMC

Zhou, Y. et al. Impairment of the glymphatic pathway and putative meningeal lymphatic vessels in the aging human. PubMed

Han, G. et al. Age- and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods. PubMed PMC

Postuma, R. B. et al. MDS clinical diagnostic criteria for Parkinson’s disease. PubMed

Dusek, P. et al. Clinical characteristics of newly diagnosed Parkinson’s disease patients included in the longitudinal BIO-PD study.

Berry, R. B. et al. For the American Academy of Sleep Medicine,

American Academy of Sleep Medicine.

Allen, R. P. et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria–history, rationale, description, and significance. PubMed

Hua, K. et al. Tract probability maps in stereotaxic spaces: analyses of white matter anatomy and tract-specific quantification. PubMed PMC

Jenkinson, M., Beckmann, C. F., Behrens, T. E., Woolrich, M. W. & Smith, S. M. Fsl. PubMed