Exercise Targeting Cognitive Impairment in Parkinson's Disease

Mild cognitive impairment (MCI), particularly of the executive function (EF) subtype, is
common in Parkinson's disease (PD) and transitions to dementia, increased fall risk, and poor
quality of life. EF is a set of processes that include mental flexibility and attention that
are needed to learn and optimize performance of complex cognitive and motor skills. Such
skills include the ability to generalize task performance under different conditions (context
processing) and to perform two tasks simultaneously termed dual-task (DT) performance.
Deficits in EF lead to problems in daily functioning and loss of independence and create
psychosocial and economic burdens on patients and caregivers and stakeholders including
health care providers. There is currently no effective treatment in PD to address EF
deficits. Our animal and clinical studies in PD demonstrate that skilled exercise facilitates
neuroplasticity of the basal ganglia (BG), a brain region sub-serving EF and supports the
hypothesis that exercise will reverse EF deficits in PD. Furthermore, recent studies in
healthy aging support that skill-based exercise that specifically promotes motor skill
fitness (MSF), compared with aerobic exercise that promotes cardiovascular fitness (CF), has
a greater impact on EF and related BG circuits. The aim of this application is to compare and
elucidate the effects of skill-based versus aerobic exercise versus control on MCI of the EF
subtype in PD; we hypothesize that skill-based exercise will result in the greatest
improvement in EF and lead to modification of underlying neural substrates.

Inclusion Criteria:

- willing and able to provide informed consent

- confirmed diagnosis of idiopathic PD based on the United Kingdom Brain Bank criteria

- Mild cognitive impairment (Level II criteria Movement Disorder Task Force)

- medically eligible for MRI imaging

- able to provide a written medical clearance from their primary physician to
participate in exercise

- stable PD medications for 3 months

Exclusion Criteria:

- a Hoehn & Yahr staging greater than 2.5 at screening

- severe cardiac disease (New York Heart Association classification IIIV)

- history of an abnormal stress test

- clinically significant medical or psychiatric illness

- electrically, magnetically, or mechanically activated implant (such as cardiac
pacemakers or intracerebral vascular clip)

- metal in any part of the body including metal injury to the eye

- past history of brain lesions (such as stroke)

- seizures or unexplained spells of loss of consciousness

- family history of epilepsy

- physical therapy within 6 months of the study

- symptomatic orthostatic hypotension at the screening visit

- orthopedic and other movement-influencing diseases such as arthritis or total hip
joint replacement

- requirement for central nervous system active therapies (e.g. hypnotics,
antidepressants, anxiolytics)

- moderate or severe depression or apathy using the Geriatric depression scale and
Apathy scale

- taking anticholinesterase inhibitors

- taking anticholinergic medication

- PD dementia

- Colorblindness