A 10-year study of the incidence of and factors predicting dementia in Parkinson's disease.

OBJECTIVE: To compare the incidence of dementia in PD with that of a control group without PD, and to assess the relationship between dementia and other features of PD. METHODS: The authors recruited 83 patients with PD and 50 controls, all without dementia at initial assessment, and assessed them at regular intervals over a maximum period of 122 months. Dementia was diagnosed according to objective criteria, and included a judgment by researchers masked to subject group and to variables putatively associated with dementia. RESULTS: Seventeen patients fulfilled dementia criteria; no controls did so. The cumulative proportion of PD patients becoming demented by 112 months was 0.38 (95% CI 0.20 to 0.55), or 42.6 cases per 1000 years of observation. Univariate analyses showed that incident dementia in patients with PD was associated with older age at entry into the study, greater severity of neurologic symptoms, longer duration of PD, greater disability, and male sex. The association of age at onset of PD with incident dementia was of only borderline significance. Multivariate analysis found that age at entry into the study and severity of motor symptoms were significant predictors of dementia but duration of PD and age at onset of PD were not. CONCLUSIONS: Dementia in PD is likely to reflect interaction of the neuropathology of the basal ganglia and age-related pathology. The findings do not support the division of PD into early and late-onset cases.

A controlled trial of prostaglandin E1 precursor in chronic neuroleptic resistant schizophrenic patients.

The postulated deficiency of prostaglandin E1 series (PGE1) in schizophrenia has been investigated in a controlled therapeutic trial. Twenty-one inpatients with a schizophrenic illness resistant to neuroleptic drug treatments were randomly assigned to one of three treatment conditions in a blind controlled trial of dihomo-gammalinolenic acid (DHLA), a PGE1 precursor. Patients received depot neuroleptic medication and DHLA capsules, placebo depot medication and DHLA capsules, or placebo depot medication and placebo capsules. No marked treatment effects were noticed on ratings of the patients' behaviour or symptomatology, though some clinical effects were noted in dyskinetic patients. Abnormalities in red blood cell lipids were observed in the patients entering the trial, suggesting that further investigation of an EFA/prostaglandin deficiency hypothesis in schizophrenia is worth pursuing.

Antidepressive effect of amitriptyline treatment with plasma drug levels controlled within three different ranges.

Seventy-four depressed patients were treated with amitriptyline for 4-6 weeks. Their doses were individually adjusted to maintain the sum of the plasma levels of amitriptyline (AT) and nortriptyline (NT) within one of three different ranges, randomly allocated. Allowance was made for individual plasma binding of the drugs. In the 50 patients between 25 and 65 years of age, the antidepressive response at low plasma drug levels was somewhat poorer than at medium or high levels, which were equally effective. In this age group an association was found between outcome and the individual rate of AT metabolism, expressed as "reciprocal clearance" (RC), the steady-state plasma concentration of AT plus NT divided by the daily AT dose. Good antidepressive outcome was associated with high RC. The implications of these findings for patient treatment and for the interpretation of other studies are discussed. The 18 patients between 65 and 80 years of age showed no significant differences between the effectiveness of treatment at different plasma drug levels, and no significant associations between outcome and RC.

A comparison of sulpiride, dothiepin, diazepam and placebo in the treatment of depressed out-patients.

The effects of sulpiride, dothiepin, diazepam and placebo were compared in out-patients who were suffering from depressive states of moderate severity. No major differences were found between the regimens after 4 weeks administration. A notable finding was the high recovery rate among those patients who received the placebo. The need for drug treatment in the milder depressive states is discussed.

Facial expressions and Parkinson's disease.

Patients with Parkinson's disease (PD) and matched control subjects were photographed posing a range of facial expressions. The same subjects were later asked to identify the posed expressions of the other subjects. They were also asked to rate the quality of expressions posed by the control subjects after being told what each expression was. Expressions posed by healthy control subjects were more readily identifiable than expressions posed by Parkinson's patients, but the two groups did not differ in their ability to recognize facial expressions or in the goodness ratings they gave, and their error patterns were closely similar. There was no significant difference between the groups on other tests of face processing or on ratings of emotionality except for greater reported anxiety in the Parkinson's patients. We conclude that although patients with PD have reduced facial expressiveness, there is no apparent diminution in their comprehension of facial expressions or their day-to-day experience of emotion.

Continuation therapy with tricyclic antidepressants in relapsing depressive illness.

Patients who have suffered a depressive illness frequently relapse when treatment is stopped. A controlled study of continued medication after clinical recovery was carried out. Of 92 patients studied, 22% of those who received amitriptyline or imipramine relapsed during 6 months of observation, compared with 50% of those who received placebo. Patients who experienced persistent residual symptoms derived more benefit from the active drug during continuation treatment than those who made a complete recovery from their illness.

Assessment of drugs in schizophrenia. Asessment of drug-induced extrapyramidal reactions and of drugs given for their control.

I have tried to bring out some of the important methodological problems found in examining the effectiveness of drugs used in the control of druginduced parkinsonism by referring mainly to studies in which I have taken part. I hope I have shown that the whole topic is far less well understood than is often assumed. The main points may be summarized as follows: there is doubt as to whether many of the drugs used in controlling drug-induced parkinsonism are really effective; the results of many studies are conflicting; many studies contain serious flaws in design; methods for assessing extrapyramidal signs are not well developed; we are ignorant of the way in which drug-induced extrapyramidal signs change spontaneously. There is a clear need for further research in this area to improve techniques of assessment, to provide basic information on drug-induced syndromes, and to rigorously examine the efficacy of the drugs used in controlling them.