Mild Cognitive Impairment and Endurance Exercise in Parkinson's Disease

The overall purpose and objective of this project is to test the hypothesis that high
intensity endurance exercise causes beneficial brain adaptation in patients with mild
cognitive impairment in Parkinson's disease (PD-MCI). Aim 1 will determine the effect of high
intensity endurance exercise on cognitive function and other clinical symptoms in PD-MCI. Aim
2 will determine the effect of high intensity endurance exercise on brain structure and
function in PD-MCI. Aim 3 will determine the effect of high intensity endurance exercise on
cortisol in PD-MCI. Aim 4 will determine the effect of high intensity endurance exercise on
inflammation-related biomarkers found in blood in PD-MCI. Aim 5 will determine the effect of
high intensity endurance exercise on peripheral levels of neurotrophic factors found in blood
in PD-MCI.

Inclusion Criteria:

- Male or female, ages 40-85

- A diagnosis of idiopathic PD

- A diagnosis of PD-MCI

- Due to the stringent head motion during fMRI, we will only include a patient with a
head tremor of < 2.

- Hoehn and Yahr stage < or equal to 3

- Stable medication regimen for > or equal to 30 days before entering the study

- Living with a carepartner

Exclusion Criteria:

- PD subjects meeting MDS criteria for PD dementia or having a SCOPA-Cog score less than
or equal to 16, or PD subjects having normal cognition defined as a SCOPA-Cog Score of
is greater or equal to 25.

- Atypical or secondary parkinsonism as determined by referring Neurologist

- Other disorders that might interfere with ability to perform high intensity endurance
exercise (e.g. history of stroke, respiratory problems, traumatic brain injury, known
advanced osteoarthritis, or neuromuscular disease).

- Individuals with known injury, disease, or condition that would affect the ability to
perform endurance exercise.

- Any other clinically significant medical condition, psychiatric condition, drug or
alcohol abuse that would, in the judgment of the investigator, interfere with the
subject's ability to participate in the study.

- "Vigorous athletes" participating in any exercise program 2X/week or more will be
excluded.

- Individuals with any type of implanted electrical device (such as a cardiac pacemaker
or a neurostimulator), or a certain type of metallic clip (i.e., an ° Persons who have
had a long history of working in metal shops will be excluded unless they have had a
previous orbital x-ray scan clearing them for participation in MRI studies.

- Females who are pregnant or might be pregnant will be excluded from participation.

- Individuals who are claustrophobic and unable to tolerate a brain MRI scan will be
excluded.

- Treatment with cholinesterase inhibitors or memantine (i.e., medications approved for
treatment of dementia) or medications affecting cognition (i.e., anticholinergics)

- Use of medications that might interfere with neuromuscular junction function such as
D-penicillamine and aminoglycoside antibiotics.

- Use of medications that might interfere with the BOLD contrast or heart response to
exercise (e.g. β blockers).

- Individuals at high risk for cardiovascular disease as defined in Table 2.2 by the new
ACSM guidelines.(Medicine 2014)

- Younger than 40 and older than 85. We exclude participants younger than 40 because
these young onset patients may not be typical of the majority of patients who get the
disease later in life. We exclude participants older than 85 because of the limited
evidence they can successfully complete a high-intensity endurance exercise program.
We also exclude patients whose disease was diagnosed before the age of 40.

- Individuals with known endocrine abnormalities or steroid use that could affect
cortisol levels (e.g., Cushing's syndrome, pituitary or adrenal gland disease or
adrenalectomy, use of steroid-based medications.

- Individuals with strong history of chronic inflammatory or autoimmune diseases or
history of chronic use of NSAIDs, which could cause abnormal levels of inflammatory
markers in the plasma.

- We will exclude adults unable to consent, individuals who are not yet adults, pregnant
women, prisoners and children from this study.