Investigating the Cholinergic Contribution to Gait Dysfunction in Parkinson's Disease

Eligibility Criteria

• 1. Diagnosis of PD by a neurologist as per UK Brain Bank criteria
• 2. Age 40 or older
• 3. Clinical evidence of gait dysfunction, as determined by a movement disorders neurologist.
• 4. Willingness and ability to comply with scheduled visits and study procedures.
• 5. Actively treated with a stable dose of levodopa or other anti-parkinsonian medications.
• 6. Able to ambulate without the use of an assistive device.
• 7. Serum chemistry from blood obtained at screening will need to be free from evidence of renal injury (elevated creatinine) or other significant metabolic abnormalities at the discretion of the examiner within 28 days of study initiation.
• 8. Subject agrees not to participate in another study with an investigational drug/treatment during this study and for 3 months following study completion.
• 9. Female subjects must not be breastfeeding and must have a negative serum pregnancy test at Visit 1. Women of childbearing potential (WOCBP) must use one of the following acceptable birth control methods as specified before enrollment and throughout the trial:
• * Surgical sterilization (bilateral tubal occlusion/ligation) prior to signing the informed consent form (ICF).
• * Intrauterine device in place for at least 3 months before the first dose of study drug and throughout the trial.
• * Barrier method (condom or diaphragm) with spermicide for at least 30 days before the first dose of the study drug and throughout the trial.
• * Surgical sterilization of the male partner (vasectomy at least 6 months before the first dose of study drug).
• * Hormonal contraceptives with a barrier method for at least 3 months before the first dose of the study drug and throughout the trial.
• * They have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at minimum one menstrual cycle prior to signing the ICF.
• * They are postmenopausal, defined as 1 year since the last menstrual period without an alternative medical cause or have a follicle-stimulating hormone (FSH) level in the menopausal range (defined as \>20 miU/mL and \<122 miU/mL) in women who are not using hormonal contraception or hormonal replacement therapy and are ≥50 years of age.
• * For women ≤50 years old, ≥2 years since her last menstrual period without an alternative.
• 1. Current use of donepezil, rivastigmine, galantamine, or memantine
• 2. Score of 3 or higher on the Anticholinergic Cognitive Burden Scale
• 3. Presence of a deep brain stimulator, or implantation of a deep brain stimulator during the study
• 4. Montreal Cognitive Assessment (MoCA) score less than 21
• 5. Known allergic reactions to donepezil or piperidine derivatives
• 6. Use of a different investigational drug/treatment within 3 months before the study
• 7. Presence of bradycardia for bradycardia (\<60bpm) and other significant arrhythmias (not counting simple first-degree heart block), severe COPD, severe asthma, peptic ulcer disease, or other severe, acute medical comorbidities that could affect the outcome of the study, for example acute end-stage CHF or acute pneumonia
• 8. Inability to obtain a brain MRI (presence of ferromagnetic metal inside the body, severe claustrophobia, etc)
• 9. Impairment in cognitive or decision-making abilities that would impede the participant's ability to consent for themselves. Of note, physical impairment or disability may still require the use of a legally authorized representative or surrogate, and would not in itself be an exclusion.