MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease

Joel Ramirez; Melissa F Holmes; Courtney Berezuk; Donna Kwan; Brian Tan; Derek Beaton; Christopher J M Scott; Miracle Ozzoude; Fuqiang Gao; Di Yu; Walter Swardfager; Jane Lawrence-Dewar; Dar Dowlatshahi; Gustavo Saposnik; Mark I Boulos; Brian J Murray; Sean Symons; Robert Bartha; Sandra E Black; Richard H Swartz; ONDRI Investigators; Andrew Lim

doi:10.1016/j.sleep.2021.03.043

MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease

Sleep Med. 2021 Jul:83:83-88. doi: 10.1016/j.sleep.2021.03.043. Epub 2021 Apr 19.

Authors

Joel Ramirez¹, Melissa F Holmes², Courtney Berezuk³, Donna Kwan⁴, Brian Tan⁵, Derek Beaton⁵, Christopher J M Scott², Miracle Ozzoude², Fuqiang Gao², Di Yu⁶, Walter Swardfager⁶, Jane Lawrence-Dewar⁷, Dar Dowlatshahi⁸, Gustavo Saposnik⁹, Mark I Boulos¹⁰, Brian J Murray¹¹, Sean Symons¹², Robert Bartha¹³, Sandra E Black¹⁰, Richard H Swartz¹⁰; ONDRI Investigators; Andrew Lim¹⁰

Collaborators

ONDRI Investigators:
Michael Strong, Peter Kleinstiver, Natalie Rashkovan, Susan Bronskill, Sandra E Black, Michael Borrie, Elizabeth Finger, Corinne Fischer, Andrew Frank, Morris Freedman, Sanjeev Kumar, Stephen Pasternak, Bruce Pollock, Tarek Rajji, Dallas Seitz, David Tang-Wai, Carmela Tartaglia, Brenda Varriano, Agessandro Abrahao, Marvin Chum, Christen Shoesmith, John Turnbull, Lorne Zinman, Jane Lawrence-Dewar, Donna Kwan, Brian Tan, Julia Fraser, Bill McIlroy, Ben Cornish, Karen Van Ooteghem, Frederico Faria, Manuel Montero-Odasso, Yanina Sarquis-Adamson, Alanna Black, Barry Greenberg, Wendy Hatch, Chris Hudson, Elena Leontieva, Ed Margolin, Efrem Mandelcorn, Faryan Tayyari, Sherif Defrawy, Don Brien, Ying Chen, Brian Coe, Doug Munoz, Alisia Bonnick, Leanne Casaubon, Dar Dowlatshahi, Ayman Hassan, Jennifer Mandzia, Demetrios Sahlas, Gustavo Saposnik, Richard H Swartz, David Breen, David Grimes, Mandar Jog, Anthony Lang, Connie Marras, Mario Masellis, Tom Steeves, Dennis Bulman, Allison Ann Dilliott, Mahdi Ghani, Rob Hegele, John Robinson, Ekaterina Rogaeva, Sali Farhan, Rob Bartha, Hassan Haddad, Nuwan Nanayakkara, Joel Ramirez, Christopher Scott, Sean Symons, Courtney Berezuk, Melissa Holmes, Sabrina Adamo, Miracle Ozzoude, Mojdeh Zamyadi, Stephen Arnott, Derek Beaton, Malcolm Binns, Wendy Lou, Pradeep Raamana, Stephen Strother, Kelly Sunderland, Athena Theyers, Abiramy Uthirakumaran, Guangyong Gy Zou, Sujeevini Sujanthan, Mojdeh Zamyadi, David Munoz, Roger A Dixon, John Woulfe, Brian Levine, Paula McLaughlin, J B Orange, Alicia Peltsch, Angela Roberts, Angela Troyer

Affiliations

¹ Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada. Electronic address: joel.ramirez1@sunnybrook.ca.
² Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
³ Psychological Clinical Science, University of Toronto Scarborough, ON, Canada.
⁴ Queen's University, Centre for Neuroscience Studies, Kingston, ON, Canada.
⁵ Rotman Research Institute, Baycrest Health Sciences Centre, Toronto, ON, Canada.
⁶ Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
⁷ Thunder Bay Regional Health Research Institute, Thunder Bay, ON, Canada.
⁸ Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁹ Stroke Outcomes and Decision Neuroscience Research Unit, Division of Neurology, St. Michael's Hospital, University of Toronto, ON, Canada.
¹⁰ Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, ON, Canada.
¹¹ Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, ON, Canada.
¹² Department of Medical Imaging, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹³ Centre for Functional and Metabolic Mapping, Robarts Research Institute, Department of Medical Biophysics, University of Western Ontario, ON, Canada.

PMID: 33991894
DOI: 10.1016/j.sleep.2021.03.043

Abstract

Objectives: Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior.

Methods: We analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index.

Results: Individuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38-22.26, p = 0.018).

Conclusions: Individuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.

Keywords: Glymphatic system; Perivascular spaces; Sleep quality; Small vessel disease; Vascular cognitive impairment; Virchow-Robin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Cerebral Small Vessel Diseases*
Cerebrovascular Disorders* / complications
Cerebrovascular Disorders* / diagnostic imaging
Glymphatic System*
Humans
Magnetic Resonance Imaging
Neurodegenerative Diseases*
Ontario
Sleep