Exploring the Effects of Exercise on Memory and Cognition in Parkinson´s Disease
NCT Number: NCT06580977
Acronym: EMCo
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Parkinson Disease
Interventions: BEHAVIORAL: cardiovascular training|BEHAVIORAL: stretching
Sponsor: Heidelberg University
Collaborators: German Foundation for Neurology|University Hospital Heidelberg|Universitätsmedizin Mannheim|SRH Kurpfalzkrankenhaus Heidelberg
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-02-27
Completion Date: 2027-07
Locations: Heidelberg University, Heidelberg, Baden-Wuerttemberg, 69120, Germany

Summary:
The study aims to assess the effects of cardiovascular (aerobic) training on memory formation and cognitive function in people with Parkinson's disease. Participants will be randomly allocated to one of two groups either performing cardiovascular training (experimental group) or stretching (control group) for twelve weeks, three times a week. The primary aim is to examine whether moderate-intense cardiovascular training (MICT) improves procedural memory formation (primary outcome) compared to stretching. Secondary outcomes include episodic memory formation, cognitive function, cardiorespiratory fitness, sleep quality, and brain-derived neurotrophic factor (BDNF) blood concentration levels.

Primary Outcome Measures: Non-declarative, procedural memory (motor sequence learning) global learning score - Visuomotor Serial Targeting Task (VSTT), To evaluate non-declarative (procedural) memory formation, a Visuomotor Serial Targeting Task (VSTT) will be used, which is widely applied to study motor sequence learning. A global motor learning score (i.e., \[relative\] change from start of encoding to 24h recall test) will be calculated for explicit (i.e., correct anticipatory movements defined as movements with onset times lower than in random trials and directed to the correct target \[directional error at peak velocity \<22°\]) and implicit (i.e., spatial error to target defined as shortest distance of the movement end point from the center of the target) components of motor sequence learning and the change (delta) in the global motor learning scores from pre- to post-assessment will be analyzed. Hence, two outcome measures from the VSTT are considered to answer the primary research question: (i) change in explicit global motor learning score, and (ii) change in implicit global motor learning score from pre- to post-assessment., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)
Secondary Outcome Measures: Non-declarative, procedural memory (motor sequence learning) encoding and consolidation - Visuomotor Serial Targeting Task (VSTT), To evaluate the effects on the different processes of non-declarative (procedural) memory formation, the encoding (i.e., relative change in performance from beginning to end of practice) and consolidation (i.e., relative change in performance from end of practice to a 24h recall test) of the motor sequence will be investigated for the implicit and explicit components, respectively. This results in four secondary outcome variables for the VSTT: (i) change in encoding of the explicit component from pre- to post assessment; (ii) change in encoding of the implicit component from pre- to post assessment; (iii) change in consolidation of the explicit component from pre- to post assessment; (iv) change in consolidation of the implicit component from pre- to post-assessment., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Declarative, episodic memory (verbal learning) - Rey Auditory Verbal Learning Test, To evaluate the effects on declarative (episodic) memory, the German version of the Rey Auditory Verbal Learning Test will be used. Similar to non-declarative (procedural) memory (i) the change in global episodic learning score (i.e., correctly recalled words at 24 h recall test) from pre- to post-intervention will be analyzed in a first step followed by a separate analysis of (ii) the change in encoding (i.e., correctly recalled words after listening five times to the wordlist) from pre- to post-intervention and (iii) the change in consolidation (i.e., change in correctly recalled words from end of encoding to recall test) from pre- to post-intervention., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Cognitive function, To evaluate the effects on cognitive function, the domains: (i) short-term memory (Digit and Spatial Span Task forward: length of correctly reproduced sequence of digits/locations), (ii) working memory (Digit and Spatial Span Task backward: length of correctly reproduced sequence of digits/locations), (iii) inhibition (Stroop Test interference score: number of correctly named colors in the color-word condition compared to the predicted color-word score), and (vi) cognitive flexibility (Trail Making Test A \& B trail flexibility score: time to complete test B compared to test A) will be assessed. A composite score including all domains to analyze change in global cognitive function from pre- to post-assessment will be calculated followed by a separate analysis of the change in the individual test scores from pre- to post-assessment., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Cardiovascular fitness, To evacuate the effects on cardiorespiratory fitness, a graded exercise test (GXT) on a cycle ergometer with spiroergometry will be performed and the change in peak oxygen consumption (VO2peak) from pre- to post intervention will be analyzed., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Objective sleep efficiency, To evaluate the effects on objective sleep quality, the change in sleep efficiency from pre- to post-assessment using wrist-worn actigraphy (ActiGraph GT9X; ActiGraph; Pensacola; USA) will be assessed., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Subjective sleep disturbance, To evaluate the effects on subjective sleep quality, the change in subjective disease-related sleep disturbance from pre- to post-assessment using the Parkinson's Disease Sleep Scale 2 (PDDS-2) total score will be assessed., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Brain-derived neurotrophic factor (BDNF) blood concentration level, To evaluate the effects on brain-derived neurotrophic factor (BDNF), serum blood samples at rest will be collected and the change from pre- to post-assessment will be analyzed., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)
Other Outcome Measures: Non-declarative, procedural memory (motor sequence learning) further variables - Visuomotor Serial Targeting Task (VSTT), In addition to the (a) number of correct anticipatory movements and (b) spatial error to target (i.e., primary outcomes), (i) onset time (i.e., time between target display and out movement start), (ii) movement time (i.e., time from out movement start to end), (iii) peak velocity, (iv) directional error at peak velocity (i.e., angular deviation between real and ideal movement trajectory at peak velocity), (v) spatial error to ideal movement (i.e., root mean squared error between real and ideal movement trajectory), and (vi) normalized hand-path area (i.e., area enclosed by the out and in movement divided by the squared path length) will be inspected to analyze practice-related changes in temporal and kinematic movement characteristics., Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Sociodemographic & physical characteristics, 1. Age, biological sex
2. Years of education
3. Height, weight, body mass index
4. Handedness (Edinburgh Handedness Inventory), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Non-motor symptoms (nonmotor experiences of daily living) - Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I, Movement Disorder Society Unified Parkinson's Disease Rating Scale (UPDRS) Part I total score (0-52), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Motor symptoms (motor examination) - Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, Movement Disorder Society Unified Parkinson's Disease Rating Scale (UPDRS) Part III total score (0-132), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Total daily medication - Levodopa equivalent daily dose, Total levodopa equivalent daily dose (LEDD) in mg, Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Cognitive status - Montreal Cognitive Assessment, Montreal Cognitive Assessment (MoCA) total score (0-30 points), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Quality of life - Parkinson´s Disease Questionnaire-39, Parkinson´s Disease Questionnaire-39 (PDQ-39) dimension scores (0-100) and total score (0-100), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Objective sleep quality, Actigraphy (wrist-worn accelerometer for seven days and nights): sleep onset latency, total sleep time, wake after sleep onset, number of awakenings, Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Subjective sleep quality, Pittsburgh Sleep Quality Index (PSQI) total score (0-21 points), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Daytime sleepiness, Epworth Sleepiness Scale (ESS) total score (0-10 points), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Severity of depression - Beck Depression Inventory, Beck Depression Inventory (BDI) total score (0-63), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Severity of anxiety - Beck Anxiety Index, Beck Anxiety Index (BAI) total score (0-63), Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Objective physical activity, Actigraphy (wrist-worn accelerometer for seven days): total volume of physical activity, steps per day, minutes spent at different intensity levels, total daily vector magnitude counts, Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Subjective physical activity last week, International Physical Activity Questionnaire (IPAQ) - short form: MET hours per week, Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)|Subjective physical activity last four weeks, German Physical Activity Questionnaire 50+ (German PAQ 50+): MET hours per week, Week 1-2: pre-assessment (baseline within two weeks before intervention), Week 15-16: post-assessment (within two weeks after intervention)