Exploring the Effects of Exercise on Memory and Cognition in Parkinson´s Disease

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.

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.

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.

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.

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.

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.

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.

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.

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.

• Age, biological sex
• Years of education
• Height, weight, body mass index
• Handedness (Edinburgh Handedness Inventory)

Movement Disorder Society Unified Parkinson's Disease Rating Scale (UPDRS) Part I total score (0-52)

Movement Disorder Society Unified Parkinson's Disease Rating Scale (UPDRS) Part III total score (0-132)

Total levodopa equivalent daily dose (LEDD) in mg

Montreal Cognitive Assessment (MoCA) total score (0-30 points)

Parkinson´s Disease Questionnaire-39 (PDQ-39) dimension scores (0-100) and total score (0-100)

Actigraphy (wrist-worn accelerometer for seven days and nights): sleep onset latency, total sleep time, wake after sleep onset, number of awakenings

Pittsburgh Sleep Quality Index (PSQI) total score (0-21 points)

Epworth Sleepiness Scale (ESS) total score (0-10 points)

Beck Depression Inventory (BDI) total score (0-63)

Beck Anxiety Index (BAI) total score (0-63)

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

International Physical Activity Questionnaire (IPAQ) - short form: MET hours per week

German Physical Activity Questionnaire 50+ (German PAQ 50+): MET hours per week