Effect of Cognitive Training on Gait in Parkinson's Disease

Disorders of Gait, Postural Stability and Cognition in Parkinson's Disease: Presymptomatic Detection and Targeted Rehabilitation

Physiotherapy and targeted rehabilitation are routinely performed in order to influence disorders of posture, gait and stability in Parkinson´s disease (PD), but their effects have been controversial (Keus et al. 2014; Walton wt al. 2014). Recently, several studies suggested that cognitive training can improve gait in patients with PD (Peterson et al. 2016, Heremans et al. 2013), similar to the effects seen in the elderly (Yogev-Seligmann et al. 2008; Amboni et al. 2013). Specific training programs including dual tasking with automatic verbal series, counting etc. have led to increased walking speed and improved stepping cadence, length, and duration in patients with dementia (Schwenk et al. 2010). However, since in advanced PD patients dual-task gait training has to be supervised by therapists, it is not a suitable type of therapy to be performed at home. Therefore, this study aims to verify and extend the encouraging results of the single study which showed a positive effect of cognitive function training on gait in PD (Milman et al. 2014) by exploring this effect in advanced PD patients, by assessing the effect on gait using more targeted clinical and instrumental evaluation, and by comparing two modes of therapy delivery, group and computer-based.

Background: In a pilot study, Milman et al. 2014 showed that computer-based cognitive training focusing on executive function and attention performed at home might improve selected gait parameters in early patients with Parkinson´s disease (PD). Goal 1: To explore this effect in advanced PD patients Hypothesis 1: Effect of cognitive training focusing on executive function and attention will be detected also in advanced PD patients and this effect will be larger as compared to the results published by Milman et al. 2014. Goal 2: To verify the results published by Milman et al. 2014 using more targeted clinical and instrumental gait assessment, including dual-task gait evaluation as well as instrumental testing of turn fluency (Bertoli et al. 2019). Hypothesis 2: The results published by Milman et al. 2014 will be confirmed and an effect on dual-task gait and turn fluency will be shown. Goal 3: To explore the role of the form of therapy setting, i.e. whether group setting might increase the effect of cognitive training on gait as compared to individual cognitive training at home. Such results have been shown in the case of a physiotherapy intervention by King et al. 2015. Hypothesis 3: The effect of group cognitive training on gait will be larger as compared to individual dose-matched, computer-based cognitive training performed at home. However, it remains to be determined whether the effect size difference between the two groups will outweigh the advantages of tele-rehabilitation. Design: Randomised-controlled trial Interventions: experimental group: group cognitive training focusing on executive function and attention; control group: computer-based cognitive training focusing on executive function and attention performed at home. Intervention in both groups will be dose-matched (experimental: 60 mins, 2x/week, 12 weeks; control: 30 mins, 4x/week, 12 weeks) Follow-up: at 1 and 3 months time points. Power analysis results: at least 38 patients.

The experimental group will undergo 60 minutes long cognitive training group sessions twice a week for 12 weeks focused on executive function, attention and working memory.

The control group will perform executive function, attention and working memory training similar to the experimental group but at home as instructed by their therapist using specialized software for cognitive training (Rehacom). This training will be dose matched to the experimental group, i.e. it will be performed four times a week for 30 minutes for 12 weeks. In this group, therapists will only provide coaching once a month.

Cognitive training focused on executive function, attention and working memory delivered either by the therapist in a group setting (experimental group) or by a specialized software for cognitive training (Rehacom) at home.

Patient is asked to perform TUG while subtracting 3 from a random number between 51-100; G-Walk instrumental gait assessment will be used

Patient is asked to perform 10MWT while subtracting 3 from a random number between 51-100; G-Walk instrumental gait assessment will be used

The Victoria Version of Stroop Test (VST): Dot Time Score (in seconds) Neutral Word Time Score (in seconds) The Victoria Version of Stroop Test (VST): Dot Time Score (in seconds) Neutral Word Time Score (in seconds)

The Victoria Version of Stroop Test (VST): Color Word Time Score (in seconds) Error score on VST Color Word Task, Total score

Change from post-intervention instrumental assessment of turn fluency during rapid turns at 1 month follow-up

Change from post-intervention instrumental assessment of turn fluency during rapid turns at 3 months follow-up

Patient is asked to perform TUG while subtracting 3 from a random number between 51-100; G-Walk instrumental gait assessment will be used

Patient is asked to perform TUG while subtracting 3 from a random number between 51-100; G-Walk instrumental gait assessment will be used

Patient is asked to subtract 3 from a random number between 51-100 while seated. This assessment is used as a reference value for TUG-DT and 10MWT-DT

Scale evaluating various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications.

Auditory Verbal Learning Test (AVLT): T1 (Try) T2 T3 T4 T5 T1-5 Total score Interfence, Total score T6, Total score Delayed recall, Total score Recognition, Correct answers total score, False answers total score

Phonemic Verbal Fluency FAS, letters: K, P, S Letter K, Total score Letter P, Total Score Letter S, Total score Letters K, P, S, Total score

Digit Span Forward, Wechsler Adult Intelligence Scale-Revised, Total score Digit Span Forward, Wechsler Adult Intelligence Scale-Revised, Total score

Assessing of visual-motor coordination. The Grooved Pegboard is a manipulative dexterity test consisting of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted.

Self-assessment quality of life scale for patients with Parkinson's disease. Patient fills it at home.

Assessing of visual-motor coordination. The Grooved Pegboard is a manipulative dexterity test consisting of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted.

Exploratory assessment of relationship between clinical effects of cognitive training and blood signature of polymorphisms in PD-related genes

Custom genetic panel (SureSelect, Agilent) for mutational analysis of 177 genes (including APOE, MAPT, GBA LRRK2, etc.)

Inclusion Criteria: diagnosis of Parkinson´s disease (PD) PD duration ≥8 years mild cognitive impairment stable medication presence of freezing of gait according to the FoG-Q AND/OR Rapid Turns Test Exclusion Criteria: dementia deep brain stimulation, pump therapy with Duodopa or Apomorphine severe fluctuations with ON state duration for less than 2 hours dopa dysregulation syndrome impulse control disorder untreated depression benzodiazepines except for single dose at night non-compliance inability to walk without support significant co-morbidities likely to affect gait, e.g., acute illness, orthopedic disease, significant visual problems, or a clinical history of stroke involvement in other treatment trials not meeting inclusion criteria

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