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

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.

• Progressive Resistance Training (PRT) (Other), also known as PRT: PD subjects may be randomized (1:1) to PRT with supervised sessions 3 times per week for 12 weeks. Exercise training will consist of a combination of resistance training (RT) and bodyweight functional mobility exercises with limited rest intervals. The full volume exercise prescription will consist of: 1) five movements to improve strength and muscle mass each performed for 3 sets of 8-12 repetitions; 2) trunk exercises to improve postural stability; and 3) 3-4 bodyweight exercises to improve power and balance. Change in slow wave sleep (SWS) from baseline to 12-weeks will be used to determine the assignment in the second 12-week period. Subjects with an increase in SWS by >24 minutes will continue in PRT for the 2nd 12 weeks of the trial, while participants with <24 minutes increase in SWS will transition to endurance training (ET).
• Delayed Exercise Training (DE) (Other): PD subjects randomized to the exercise control group (1:1) will not exercise during the first 12 weeks of the study. During that time, they will be asked not to change their physical activity levels or dietary habits. All participants in the delayed-exercise group will begin PRT at completion of the 1st 12-week period.
• Endurance Training (ET) (Other), also known as ET: Non-responders to PRT will transition too ET during 2nd 12 weeks of the study. This intervention is supervised endurance training, 3 times per week for 12 weeks. Each session lasts approximately 75 min., comprised of warm-up, stimulus phase for 50-60 min., and cool-down. Sessions are split between cycle ergometer and treadmill exercise. Participant heart rate is monitored to maintain target exercise intensity of 60-80% (±5%) of heart rate reserve (HRR).

Primary outcomes

• Change in Cognition in Stroop inhibition [Baseline to twelve weeks]: Change in executive function on the Stroop inhibition

Secondary outcomes

• Change in slow wave sleep (SWS) [Change from baseline to twelve week and change from twelve weeks to 24 weeks.]: Change in slow wave sleep as measured by polysomnography

Sex: All, ages: 45 Years to 100 Years

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.

• Amy Amara, MD, PhD, Principal investigator, University of Colorado, Denver

NIH grants: R01HD100670