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Levodopa improves motor function without impairing cognition in mild non-demented Parkinson's disease patients

From Massachusetts General Hospital (Dr. Growdon), Boston; the Departments of Neurology (Dr. Kieburtz) and Biostatistics (Dr. McDermott), University of Rochester, NY; the McGill Centre for Studies in Aging (Dr. Panisset), Verdun, Quebec, Canada; and the Department of Neurology (Dr. Friedman), Memorial Hospital of Rhode Island, Pawtucket.

Address correspondence and reprint requests to Dr. Growdon, Massachusetts General Hospital, WAC 830, Boston, MA 02114.

Objective: The objective of the study was to determine the effects of short-term levodopa administration on motor, cognitive, and psychiatric aspects of Parkinson's disease (PD).

Background: The effects of levodopa on mental processes in PD are controversial. Opinions range from the claim that levodopa improves cognition to the opposite view that levodopa causes or exacerbates dementia, delusions, and hallucinations. Of the 800 idiopathic PD patients enrolled in the original DATATOP study, 387 reached the end point of functional disabilities sufficiently severe to require levodopa treatment. There were 263 men and 124 women who were comparable with regard to age, symptom duration of PD, and measures of PD severity. We compared test scores on motor performance, cognitive function, and psychiatric status before levodopa and again within 6 months after initiation of levodopa therapy.

Results: Levodopa administration improved all motor functions significantly. The improvement was significantly greater in women than in men. Levodopa administration did not worsen scores on any cognitive tests, and there were quantitatively small but significant improvements in tests of frontal lobe function. Levodopa exerted only minor effects on psychiatric measures. There were small but significant decreases in scores for depression, and increases in vivid dreams and hallucinations.

Conclusions: Levodopa administration for up to 6 months in dosages sufficient to improve motor function has only small effects on cognitive function and psychiatric status in mild to moderate PD patients. We conclude that motor symptoms in early PD, which result from dopamine depletion, are dissociable from cognitive functions and psychiatric status, which may be more dependent on nondopaminergic mechanisms.

*See the Appendix on page 1330 for a list of the investigators and institutions of the Parkinson Study Group.

Supported primarily by Public Health Service grant NS 24778 from the National Institute of Neurological Disorders and Stroke, and by site grants from the General Clinical Research Centers Program of the National Institutes of Health.

Received August 25, 1997. Accepted in final form November 18, 1997.

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