Efficacy of rivastigmine for cognitive symptoms in Parkinson disease with dementia.
BACKGROUND
Impairment of multiple neurotransmitter networks, including acetylcholine, may contribute to the cognitive impairment in patients with Parkinson disease with dementia (PDD). Therefore, cholinesterase inhibitors might improve cognitive function in PDD. On the other hand, enhancing cholinergic function could plausibly worsen features of parkinsonism.


OBJECTIVE
To determine if oral cholinesterase inhibitors improve measures of cognitive outcome and are tolerated by people with PDD.


METHODS
We addressed the question through the development of a critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, a medical librarian, and behavioral neurology and movement disorder specialists. Participants began with a structured clinical question, devised search strategies, compiled the best evidence, performed a critical appraisal, summarized the evidence, provided commentary, and declared bottom-line conclusions.


RESULTS
A randomized controlled trial (n = 541) showed that, compared with placebo, rivastigmine (mean, 8.6 mg/d) significantly improved scores on 2 coprimary cognitive outcome scales in PDD, including the Alzheimer disease Cooperative Study-Clinician's Global Impression of Change. When dichotomized to evaluate clinically significant benefit (moderate or marked improvement), this outcome was not significant (risk difference = 5.3%; 95% confidence interval (CI) = -1.6 to 12.1). The number needed to treat (NNT) to avoid clinically significant worsening of cognition was 10 (95% CI = 6-28). The NNT for the combined outcome of either achieving clinically significant benefit or avoiding significant worsening was 7. The numbers needed to harm for cholinergic side effects were 9 (95% CI = 5-24) for parkinsonian symptoms and 11 (95% CI = 6-32) for rivastigmine discontinuation due to any side effect.


CONCLUSIONS
Rivastigmine therapy for PDD is associated with significant tradeoffs in efficacy and adverse effects. Carefully monitored trials of rivastigmine may provide meaningful benefits for a minority of PDD patients.
Almaraz
Amy C
AC
Department of Neurology, Mayo Clinic, Scottsdale, Arizona 85259, USA.
Driver-Dunckley
Erika D
ED
Woodruff
Bryan K
BK
Wellik
Kay E
KE
Caselli
Richard J
RJ
Demaerschalk
Bart M
BM
Adler
Charles H
CH
Caviness
John N
JN
Wingerchuk
Dean M
DM
D000109:Acetylcholine / Q000172:deficiency; D000284:Administration, Oral; D000368:Aged; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications* / Q000523:psychology; D008297:Male; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000469:parasitology; D048448:Phenylcarbamates / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D000068836:Rivastigmine; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D010919:Placebos; D000109:Acetylcholine; D000068836:Rivastigmine