Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults

Abstract

Background and Objectives:The glymphatic system, which is robustly enabled during some stages of sleep, is a fluid-transport pathway that clears cerebral waste products. Most contemporary knowledge regarding glymphatic system is inferred from rodent experiments and human research is limited. The objective of the research is to explore the associations between human glymphatic function, sleep, neuropsychological performances, and cerebral gray matter volumes.Methods:This cross-sectional study included individuals 60 years or older who had participated in the Integrating Systemic Data of Geriatric Medicine to Explore the Solution for Health Aging study between September 2019 and October 2020. Community-dwelling older adults were enrolled at 2 different sites. Participants with dementia, major depressive disorders, and other major organ system abnormalities were excluded. Sleep profile was accessed using questionnaires and polysomnography. Administered neuropsychological test batteries included Everyday Cognition (ECog) and the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB). Gray matter volumes were estimated based on magnetic resonance imaging (MRI). Diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) index was used as the MRI marker of glymphatic function.Results:A total of 84 participants (mean [SD] age, 73.3 [7.1] years, 47 [56.0%] women) were analyzed. Multivariate linear regression model determined that age (unstandardized β, -0.0025 [SE, 0.0001]; P = 0.02), N2 sleep duration (unstandardized β, 0.0002 [SE, 0.0001]; P = 0.04), and the apnea-hypopnea index (unstandardized β, -0.0011 [SE, 0.0005]; P = 0.03) were independently associated with DTI-ALPS. Higher DTI-ALPS was associated with better ECog language scores (unstandardized β, -0.59 [SE, 0.28]; P = 0.04) and better CERAD-NB word-list-learning delayed recall subtest scores (unstandardized β, 6.17 [SE, 2.31]; P = 0.009) after co-varying for age and education. Higher DTI-ALPS was also associated with higher gray matter volume (unstandardized β, 107.00 [SE, 43.65]; P = 0.02) after controlling for age, gender, and total intracranial volume.Discussion:Significant associations were identified between glymphatic function and sleep stressing the importance of sleep for brain health. This study also revealed associations between DTI-ALPS, neuropsychological performances, and cerebral gray matter volumes suggesting the potential of DTI-ALPS as a biomarker for cognitive disorders.

Glymphatic System Dysfunction in Central Nervous System Diseases and Mood Disorders

“…During non-rapid eye movement (NREM) sleep, a consistent pattern of slow wave activity and CSF inflow is observed, supporting the exciting possibility that sleep regulates glymphatic function ( Fultz et al, 2019 ). Siow et al (2021) used diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) index as the MRI marker of glymphatic function, identified significant associations between glymphatic function and sleep in 84 elderly participants. However, the specific interaction between the glymphatic system and sleep remains unclear.…”

Perivascular Spaces, Glymphatic System and MR

“…Similar results have been observed in Parkinson's patients ( 92 ). Another study in a community-dwelling population of non-demented older adults showed that a higher DTI-ALPS index was associated with higher scores on the neuropsychological performance test and also with higher gray matter volume ( 93 ). Meanwhile, the significant association between glymphatic function and sleep was reconfirmed ( 93 ).…”

“…Another study in a community-dwelling population of non-demented older adults showed that a higher DTI-ALPS index was associated with higher scores on the neuropsychological performance test and also with higher gray matter volume ( 93 ). Meanwhile, the significant association between glymphatic function and sleep was reconfirmed ( 93 ). These studies suggest the promise of the DTI-ALPS index as an imaging marker for assessing cognitive impairment.…”

Author Response: Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults

“…We appreciate Dr. Kawada's constructive comments on our statistical methods. 1 We evaluated the univariate associations between diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) and the demographic/clinical variables and found that only age and pulse rate had significant association with DTI-ALPS ( p = 0.001 and p = 0.4, respectively).…”