The effects of nicotine on Parkinson's disease

Post-mortem studies have demonstrated a substantial loss of nicotinic recep tors in Parkinson's disease (PD), which may be at least partially responsib le for some of the cognitive, motoric, and behavioral deficits seen in this disorder. Epidemiologic studies have suggested that cigarette smoking is a strong negative risk factor for the development of PD. We have previously shown that blockade of central nicotinic receptors produces cognitive impai rment in areas of new learning, short-term memory, and psychomotor. slowing with increasing dose sensitivity with age and disease. Studies of acute st imulation of nicotinic receptors in Alzheimer's disease with nicotine and t he novel agonist ABT-418 in our laboratory and others have shown improvemen ts in several measures of cognitive function. Prior studies of the effects or nicotine in PD have suggested some improvements in clinical symptomatolo gy,gy. We have begun quantitative studies of both acute and chronic nicotin e in PD a, assess both cognitive and motor effects. Fifteen (15) nondemente d subjects (age 66 +/- 5.3; M/F = 11/4) with early to moderate PD (mean Hoe hn-Yahr stage = 1.77; MMSE = 28.6) received a dose-ranging study of intrave nous nicotine up to 1.25 mu g/kg/min, followed by chronic administration of nicotine by transdermal parch with closes ranging up to 14 mg per day for 2 weeks. Testing occurred both during drug administration and up to 2 month s after drug cessation to look for prolonged effects. Preliminary analysis shows improvements after acute nicotine in several areas of cognitive perfo rmance, particularly measures such as reaction time, central processing spe ed, and decreased tracking error. Improvements in attention and semantic re trieval were not seen. After chronic nicotine, improvements were seen in se veral motor measures suggesting improved extrapyramidal functioning. This a ppeared to be sustained for up to 1 month after drug. The treatment was wel l tolerated. Nicotinic stimulation may have promise for improving both cogn itive and motor aspects of Parkinson's disease. (C) 2000 Academic Press.