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Patients with Parkinson's syndrome whose major symptoms are akinesis, rigidity, inertia, depression, irritability and failure of adaptation rather than tremor appear to benefit in a global way from therapy with imipramine. Patients without much over-all functional impairment do not show this improvement. The hypothesis is offered that motivation to move and ability to move are perhaps neurologically as well as psychologically related functions.

The effects of levodopa on tests measuring auditory and visual perception, auditory, and visual short-term memory, verbal learning, and on attention and concentration were studied in 29 patients with Parkinsonism. Thirty-two control subjects matched with the Parkinsonism patients on age, educational level, and verbal IQ were administered the same tests to control for practice effects. Significant improvement occurred for the Parkinsonism patients in verbal learning (an intermediate memory test) and in auditory perception. These improvements were unrelated to changes in anticholinergic medications, increases in alertness or concentration, lessening of depression, or improved motor ability or control. There was no test evidence of levodopa improving visual perception, short-term auditory or visual memory, alertness or concentration. Thus, there is no objective test evidence for levodopa producing a generalized awakening or an alerting effect in Parkinsonism patients who are intellectually alert and well-orientated. Interpretation of the test findings suggests a specific awakening effect, that of improvement in intermediate memory but not in short-term memory. Overall, the Parkinsonism group scored below the control group on all tests, suggesting that cognitive impairment accompanies Parkinson's disease even in patients who are intellectually intact and well oriented.

One hundred patients with Parkinson's disease were treated with levodopa for more than a year at UCLA Medical Center. They were examined at given intervals and their improvement was graded. The optimum therapeutic dose was attained by balancing side effects against relief of symptoms and ranged from 1.5 grams to 8.0 grams per day (average 4.3 grams). There is no doubt that levodopa is the most effective treatment now available for Parkinson's disease. At the end of the first year, 60 percent of the patients improved 50 percent or better, and 10 percent were considered symptom-free. All major symptoms of this disease, including rigidity, akinesia and tremor, improved in variable degree. There were no serious abnormalities in the routine clinical laboratory tests. The comon side effects included nausea, vomiting and choreoathetoid dyskinesias. The side effects were not life threatening, but occasionally were major therapeutic challenges. Maximal benefits with minimal side effects were achieved only by careful adjustments of the levodopa dosage as the months went by. This needed careful management by the physician and cooperation by the patient. Anticholinergic medications or amantadine hydrochloride, sometimes both, usually supplemented the effect of the levodopa.