Tai Chi Practice and Sleep-Active Glymphatic Function - PROJECT SUMMARY/ABSTRACT Amyloid plaque deposition, a key pathological hallmark of Alzheimer’s disease (AD), begins 1-2 decades before manifestation of clinical symptoms of dementia. Among cognitively intact individuals and in AD’s most prevalent sporadic form, the production of amyloid-β (Aβ) does not change, while clearance of Aβ is slowed, indicating that the failure of Aβ clearance may underlie the development of AD pathology and that interventions that improve its clearance may provide an opportunity for primary prevention of AD. Over the past 10 years, our group has helped to define the ‘glymphatic system’, a brain-wide network of perivascular pathways along which cerebrospinal fluid (CSF) surrounding the brain exchanges with brain interstitial fluid, supporting the clearance of interstitial wastes, including Aβ and tau. Impairment of glymphatic clearance is observed in the aging brain and in mouse models of AD. Thus, improving glymphatic clearance of brain interstitial proteins may be one approach to preventing the development of AD. Glymphatic function is regulated by sleep-wake behavior, with faster clearance occurring during sleep. Tai Chi is a Chinese martial art focusing on mindful body movement, posture, and breathing as an avenue to achieve a state of internal balance, calm, and clarity. In clinical studies, practice of Tai Chi is associated with improved sleep quality, cognition, mood, cardiovascular and respiratory function, and balance/physical activity. However, the physiological processes underlying the cognitive and affective effects of Tai Chi remain undefined. We hypothesize that Tai Chi practice improves glymphatic function. To test this hypothesis, we will enroll 75 middle-aged (50-70 years) participants with different levels of Tai Chi practice experience: Tai Chi proficients (10+ year of practice, n=25), Tai Chi beginners (12 months practice, n=25) and Tai Chi naïve participants (n=25). We will 1) examine the association between Tai Chi practice and glymphatic function using multi-modal magnetic resonance imaging (MRI) using contrast-enhanced MRI, T1/FLAIR assessment of MRI-visible perivascular spaces, intravoxel incoherent motion, and fast BOLD-fMRI; 2) examine relationships between Tai Chi practice and sleep, including sleep fragmentation, efficiency, and duration, assessed by self-reported questionnaires and objective measurements of sleep duration, fragmentation and efficiency using a bed pressure mat. We will examine the relationship between sleep measures and MRI-assessed glymphatic function. The ultimate goal of this study is to elucidate mechanisms of Tai Chi practice in prevention of AD and related dementias. This pilot study will determine whether long-term Tai Chi practice is associated with physiological changes in glymphatic function and sleep. If we find cross-sectional association among Tai Chi practice, glymphatic function, and sleep, in the future we will investigate whether these changes are associated with duration of Tai Chi practice and whether these changes are associated with changes in AD biomarkers in a longitudinal study or in a prospective randomized clinical trial.
