Worsening of Motor Function and Mood in a Patient With Parkinson’s Disease After Pharmacologic Challenge With Oral Rivastigmine *Irene Hegeman Richard, *†Anne Wallace Justus, ‡Nigel H. Greig, *Frederick Marshall, and *Roger Kurlan *Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester; †Department of Clinical and Social Psychology, University of Rochester, Rochester, New York; and ‡Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, Maryland, USA Summary: Patients with Parkinson’s disease (PD) can experience cognitive impair- ment. There are currently no medications indicated for the treatment of cognitive im- pairment in PD. Clinicians are faced with the dilemma as to whether or not to treat patients with PD with the acetylcholinesterase inhibitors that are currently approved for use in Alzheimer’s disease (AD) and that have shown promise in clinical trials of De- mentia with Lewy bodies (DLB). Although these medications may help cognition, there is a theoretical concern that by increasing acetylcholine relative to dopamine, they might worsen motor function. We report the case of a patient with PD and cognitive impair- ment who developed a marked worsening of motor function, mood, and anxiety in the setting of a pharmacologic challenge study using a 3-mg oral dose of the acetylcholin- esterase inhibitor, rivastigmine. We believe that the mechanism of the motor and perhaps psychiatric worsening was increased central cholinergic tone. We conclude that further studies should be done to evaluate the efficacy and tolerability of these agents in this illness but that caution should be exercised when using acetylcholinesterase inhibitors in patients with PD. Key Words: Rivastigmine—acetylcholinesterase inhibitors— Parkinson’s disease In addition to motor difficulties, patients with Par- kinson’s disease (PD) may experience numerous non- motor symptoms, including dementia. One mechanism underlying dementia in PD may include a spread of the primary PD pathology to involve the cerebral cortex. Cortical Lewy bodies have been reported to be the most sensitive and specific correlate of dementia in the set- ting of PD, although concomitant Alzheimer’s pathol- ogy may occur in some cases (1). In Alzheimer’s dis- ease (AD), a disturbance of acetylcholine is thought to underlie the cognitive dysfunction, and acetylcholines- terase inhibitors are approved for its treatment (2). Clinicians are currently faced with the dilemma of whether or not to use acetylcholinesterase inhibitors in their patients with PD dementia. The balance between central nervous system (CNS) acetylcholine and dopa- mine appears important for PD motor function (i.e., an- ticholinergic medications are known to help PD motor features), so there is a theoretical reason to predict that acetylcholinesterase inhibitors might worsen motor symptoms. However, there have been recent studies suggesting that, in Dementia with Lewy bodies (DLB; characterized by dementia and Parkinsonism), rivastig- mine is not associated with worsened motor function. McKeith et al., (3) conducted a randomized, double- blind, placebo-controlled clinical trial of rivastigmine, concluding that this agent improved behavior without worsening motor function in patients with DLB. How- ever, patients with severe extrapyramidal symptoms Address correspondence and reprint requests to Dr. Irene Hegeman Richard, Box 673, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. E-mail: irichard@mct.rochester.edu. Clinical Neuropharmacology Vol. 25, No. 6, pp. 296–299 © 2002 Lippincott Williams & Wilkins, Inc., Philadelphia 296