Slow Wave Sleep As a Biomarker of Rehabilitation-induced Cognitive Improvement in PD

Slow Wave Sleep As a Biomarker of Rehabilitation-induced Cognitive Improvement in Parkinson's Disease R01 HD100670

The purpose of this study is to investigate the effects of exercise rehabilitation on cognition and to evaluate slow wave sleep (SWS) as a biomarker and mediator of response to rehabilitation-induced improvement in cognitive performance among persons with Parkinson's disease (PwP), with the ultimate goal of maximizing rehabilitation efficacy at the individual level (i.e. precision rehabilitation).

Sleep impairment adversely affects cognitive function and increases risk for dementia. Slow wave sleep (SWS) or delta sleep (non-rapid eye movement (REM) stage 3; N3) is especially important for cognition due to its association with synaptic plasticity, synaptic potentiation, synaptic renormalization, and cortical reorganization, especially in prefrontal cortex. Clinically, SWS contributes to memory consolidation and language performance. The investigators have previously shown that the amount of SWS in persons with Parkinson's disease (PwP) is related to cognitive performance, especially in the domain of executive function. The investigators have also shown that exercise increases SWS in some PwP and that participants who have an exercise-induced increase in SWS also have improvement in executive function. This study will evaluate changes in cognitive function and SWS due to progressive resistance training rehabilitation (PRT). Participants who do not have an increase in SWS with PRT (non-responders) over 12 weeks will be transitioned to an endurance training (ET) intervention, while those who do have an increase in SWS (responders) will continue in PRT for an additional 12 weeks.

Inclusion:

• clinical diagnosis of idiopathic PD, based on the presence of bradykinesia as well as at least one of the following: rest tremor, rigidity, and/or postural instability (per United Kingdom PD Brain Bank Criteria)
• Hoehn and Yahr stage 2-3 (performed at screening visit)
• age ≥ 45 and
• on stable medications for at least 4 weeks prior to study entry without expecting to change medications for the duration of the study.
• Montreal Cognitive Assessment (MoCA) score ≥ 18 and <26 (performed at screening visit)
• No contraindications to an exercise program.

Exclusion:

• fails exercise readiness evaluation at screening visit
• regular participation in an exercise program
• cardiovascular or pulmonary disease, including uncontrolled hypertension, congestive heart failure, unstable coronary artery disease, serious arrhythmia, stroke within the past year, or chronic obstructive pulmonary disease (COPD)
• shift workers
• signs indicative of atypical Parkinsonism (cerebellar signs, supranuclear gaze palsy, apraxia, prominent autonomic failure, or other cortical signs)
• secondary Parkinsonism (neuroleptic treatment at time of onset of Parkinsonism or at time of study entry, history of multiple strokes with stepwise progression of Parkinsonism, or history of multiple head injuries)
• inability to walk without assistance
• deep brain stimulation (DBS)
• known narcolepsy
• untreated sleep apnea
• any condition that, in the opinion of the investigator, will preclude the participant from successfully or safely completing study procedures.