This study will evaluate the safety and effectiveness of donepezil (Aricept) for treating
mild dementia in patients with Parkinson's disease. Donepezil is approved for treating
patients with Alzheimer's disease, whose memory and cognition problems are similar to those
of patients with Parkinson's disease who are affected by dementia. Donepezil prevents the
breakdown of a chemical messenger called acetylcholine, which is involved in memory and
other cognitive functions, and may improve cognition in patients.
Patients 40 years of age and older with Parkinson's disease who have mild to moderate
dementia may be eligible for this 6-month study. It involves 6 clinic visits of
approximately 2 hours each, described below. Candidates will be screened for participation
during Visit 1.
- Visit 1 (screening visit): Study candidates will have a medical history, physical and
neurological examinations, electrocardiogram (EKG), and possibly blood tests. They will
also undergo neuropsychological testing (tests of memory, language, mood and, other
brain functions) and fill out a quality of life questionnaire. Those enrolled will be
randomly assigned to receive either donepezil (5 mg per day) or placebo-a look-alike
pill with no active ingredients. After 4 weeks, the dose of donepezil will be increased
to 10 mg per day. Patients who do not tolerate the higher dose will have it reduced to
5 mg. Those who do not tolerate the 5-mg dose will be taken off medication but will
continue to be followed and tested.
- Visit 2 (week 7): Patients will have a neurological examination and neuropsychological
testing and will fill out a quality of life questionnaire.
- Visit 3 (week 10): Patients will repeat the evaluations done during visit 2 and will
stop taking the study medication.
- Visit 4 (week 16): Patients will repeat the evaluations done during visit 2 and will
have their study medication switched. That is, patients previously on placebo will be
switched to donepezil, and patients who were taking donepezil will be switched to
placebo. After 4 weeks, the dose of donepezil will be increased to 10 mg per day.
Patients who do not tolerate the higher dose will have it reduced to 5 mg. Those who do
not tolerate the 5-mg dose will be taken off medication but will continue to be
followed and tested.
- Visits 5 and 6 (weeks 23 and 26): Patients will repeat the evaluations done during
This study is being conducted at the National Institutes of Health, the University of
Pennsylvania, and Northwestern University
Parkinson's disease (PD) is the second most common neurodegenerative disorder after
Alzheimer's disease (AD). Dementia is a common problem late in the course of the disease
and there is no effective therapy. Dementia severely impairs patients'' functional status
and limits the treatment of the motor manifestations of PD. No effective therapy for
dementia in PD is available. The pathophysiology of dementia in PD is not completely
understood, however, as in AD, it is thought to be related to cholinergic dysfunction.
The proposed study will determine whether a therapeutic intervention with donepezil, an
acetylcholinesterase inhibitor, shown to be effective in AD, will improve cognitive function
in PD. The study is planned as a 26-week, randomized, double-blind, placebo-controlled,
cross-over study of the efficacy and safety of donepezil in PD with dementia. The study is
being conducted at the University of Pennsylvania, Brown University, Northwestern University
The primary outcome measure in this trial is the change in the Alzheimer's Disease
Assessment Scale-Cognitive Subscale (ADAS-cog). The secondary outcome measures will include
other scales of cognitive function, activities of daily living, mood, and quality of life.
Tolerability of the drug will be assessed based on the side effect profile, specifically,
the effect on motor performance.
Age greater than or equal to 40.
A clinical diagnosis of Idiopathic PD, stages I-IV, using British Brain Bank Research
Mild to moderate dementia with Mini Mental Status Score of 17-26.
The presence of an alternative cause of dementia such as AD or stroke, based on clinical
evaluation. Subjects will have serologic screening for reversible causes of dementia,
including syphilis, thyroid dysfunction and B12 deficiency.
Presence of uncontrolled hallucinations-hallucinations that are disruptive such that they
would interfere with cognitive testing.
Anticholinergic or cholinergic therapy within 2 weeks prior to inclusion in the study
except for Amantadine and Detrol.
Patients with unstable or clinically significant medical problems such as cardiac
arrhythmia or unstable heart disease (e.g. new onset angina) that would, in the judgment
of the investigators, interfere with the safe conduct of the study.
Patients enrolled in other protocols involving investigational drugs or surgery.
Severe depression: Geriatric Depression Scale score greater than or equal to 13.
Pregnancy or breast feeding.