Changes in Metabolic Activity, and Gait Function by Dual-task Cognitive Game-based Treadmill Intervention in Parkinson's Disease.

The present proposal will evaluate the neural underpinnings of (a) the decline of mobility function in Parkinson's disease (PD), and (b) the effects of an innovative computer-guided dual-task (DT) mobility training platform (complementary approach: exercise intervention). Improved mobility functioning in PD, specifically balance, gait and cognition, directly translates to improved community ambulation as well as increased physical activity and social participation. These benefits are known to have a significant preventive and disease-modifying impact that surpasses any currently available pharmacological interventions. Outcomes of this research will provide new insights into brain plasticity mechanisms and will accelerate further optimization and commercialization of multi-modal mobility-cognitive training applications along with accompanying smart electronic monitoring tools. With wider usage of this training platform, rehabilitation specialists will be able to effectively scale services, while still monitoring quality and ensuring accountability. Thus, the study is highly transformative.

The present proposal will evaluate the neural underpinnings of (a) the decline of mobility function in Parkinson's disease (PD), and (b) the effects of an innovative computer-guided dual-task (DT) mobility training platform (complementary approach: exercise intervention). Improved mobility functioning in PD, specifically balance, gait and cognition, directly translates to improved community ambulation as well as increased physical activity and social participation. These benefits are known to have a significant preventive and disease-modifying impact that surpasses any currently available pharmacological interventions. Outcomes of this research will provide new insights into brain plasticity mechanisms and will accelerate further optimization and commercialization of multi-modal mobility-cognitive training applications along with accompanying smart electronic monitoring tools. With wider usage of this training platform, rehabilitation specialists will be able to effectively scale services, while still monitoring quality and ensuring accountability. Thus, the study is highly transformative.

The investigators propose a collaborative project between our research centers at the University of Manitoba and the University of Toronto, to further understand the neural underpinnings of cognition/gait impairment and the effects of DT training in PD.

Cutting-edge behavioural brain imaging methods will be used to identify functional brain metabolic network re-organization and the molecular basis of gait/cognitive impairment. This will be used to evaluate the neurophysiological underpinnings of the DT treadmill training effect, which has repeatedly demonstrated to be clinically effective. The possibility of detecting these changes and localizing the site(s) of brain plasticity will have important implications at several levels. These biomarkers could be used as an indicator of disease severity, outcome measures for neuroprotection studies and other treatment and lifestyle strategies.

Objective 1: To characterize the abnormal brain metabolic pattern in PD patients during DT-walking as compared to healthy age-matched controls.

Objective 2: The investigators will examine whether a 10-week treadmill walking program combined with specific cognitive activities (i.e. true DT walking training known to improve gait function and reduce falls) will "normalize" the brain abnormality (that is identified in Aim 1), or whether it will activate a novel compensatory mechanism and therefore evidence to isolate the region(s) of brain plasticity.

The hypothesis is that the DT gait-related abnormal brain metabolic pattern and abnormally elevated amyloid deposition are inter-related and that these abnormal functional connectivity patterns and structural changes are highly associated with gait, cognitive and DT walking deficits in PD. It is also hypothesized that the DT treadmill-training program will result in specific and significant changes in the DT gait-related abnormal brain metabolic pattern, in the PD participants.

Eligibility Criteria:
Inclusion Criteria: (PD Participants)

* Diagnosed with idiopathic PD, defined by the UK Brain Bank criterion in disease stage 2 - 3 (classified by Hoehn and Yahr scale),
* Montreal cognitive assessment (MoCA) scores to be 25 or higher
* Age 55-70 years
* Stable medications for Parkinson over the past 3 months
* Able to walk at least 50m without any assistive device
* Episode of FOG in the past 6 months

Exclusion Criteria: (PD Participants)

* The presence of neurological conditions other than PD affecting cognitive abilities.
* Any orthopedic impairment affecting gait and balance.
* Any cardiovascular impairment limiting the ability to walk for 10-15 minutes on a treadmill;
* Abnormal MRI
* General contraindications.

Inclusion Criteria: (Healthy Controls)

* Age 55-70 years,
* Independent community living,
* Not receiving any home care or Physiotherapy,
* Walking outdoors for exercise for at least 3 times per week,
* No neurological conditions affecting mobility or affecting cognitive abilities,
* Any orthopedic impairment affecting gait and balance.
* Any cardiovascular impairment limiting the ability to walk for 10-15 minutes on a treadmill.
* Abnormal MRI and
* General contraindications for PET and MRI including severe dyskinesia, diabetes, cardiac pacemakers.

Exclusion Criteria (Healthy Controls):

* Any orthopedic impairment affecting gait and balance.
* Any cardiovascular impairment limiting the ability to walk for 10-15 minutes on a treadmill.
* Abnormal MRI
* General contraindications.