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

University of Colorado Denver (CU Denver)

Status: Enrolling

Conditions: Parkinson Disease

Treatments: Other: Progressive Resistance Training (PRT); Other: Delayed Exercise Training (DE); Other: Endurance Training (ET)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04796506

R01HD100670

IRB-300005901 (Other Identifier)

22-1685

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 45 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

---

120 participants in 2 patient groups, including a placebo group

Exercise Group

Active Comparator group

Description:

PD participants randomized to progressive resistance training PRT) will have 12 weeks of supervised PRT 3 times per week. After the 1st 12 weeks, responders to PRT (increase in slow wave sleep) will continue PRT for an additional 12 weeks, non-responders to PRT will transition to endurance training (ET).

Treatment:

Other: Endurance Training (ET)

Other: Progressive Resistance Training (PRT)

Delayed Exercise Group

Placebo Comparator group

Description:

PD participants randomized to the delayed exercise control group will not exercise for the 1st 12 weeks of the study. After the 1st 12 weeks, participants in the delayed exercise group will transition to PRT for the 2nd 12 weeks.

Treatment:

Other: Delayed Exercise Training (DE)

Other: Progressive Resistance Training (PRT)