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June 2004

LE Magazine June 2004
Parkinson's Disease

A population-based investigation of Parkinson's disease with and without dementia. Relationship to age and gender.
Because the prevalence of idiopathic Parkinson's disease (PD) with or without dementia remains controversial, we initiated a population-based investigation in the Washington Heights-Inwood section of New York , NY , so that nearly complete case ascertainment could be achieved. A "registry" was developed for the study, and we advertised in periodicals and on radio and television. Subjects, or their records, were examined by experienced neurologists, and most underwent a battery of neuropsychological tests specifically designed for assessment in this community. All data were reviewed by a team of clinicians to achieve a consensus diagnosis. The crude prevalence of idiopathic PD, with and without dementia, was 99.4 per 100,000, increasing from 2.3 per 100,000 for those younger than 50 years to 1144.9 per 100,000 for those aged 80 years and older. The crude prevalence for PD with dementia alone was 41.1 per 100,000 and also increased with age from zero for those younger than 50 years to 787.1 per 100,000 for those aged 80 years and older. Prevalence ratios were comparable with those of other published population-based studies in similar settings. After standardization, men had PD with and without dementia more frequently than did women. The major difference between patients with and without dementia was a later estimated age at onset of motor manifestations. We conclude that PD is a frequent disorder in the elderly population that affects men and whites more frequently than women and nonwhites. Moreover, dementia in patients with PD is more frequent than previously recognized and is strongly related to the age at onset of motor manifestations.

Arch Neurol . 1992 May;49(5):492-7

Worldwide occurrence of Parkinson's disease: an updated review.
Comparison of Parkinson's disease (PD) prevalence and incidence in various parts of the world is difficult because methods of case ascertainment, diagnostic criteria, classification, medical facilities, and age distribution of the populations vary broadly in different studies. We minimized these differences by adjusting available data to a single standard population. Using this we calculated age-adjusted rates for 27 regional populations and analyzed PD frequency from 45 communities. We conclude: (1) with the exception of China, Japan and Africa, which have the lowest prevalence ratios, the actual prevalence variation for PD is probably lower than previously reported in geographically diverse populations; (2) geographic variation is unlikely to be due exclusively to racial factors, and (3) environmental risk factors for PD might differ regionally.

Neuroepidemiology. 1993;12(4):195-208

Twin study of Parkinson disease.
Zero concordance for Parkinson disease was found in the first 12 monozygotic twin pairs examined in an ongoing twin study. One co-twin (subject without Parkinson disease) had essential tremor, another had cerebral vascular disease, and a third was an alcoholic. Cigarette smoking appeared to be less frequent in the probands than in the co-twins (11.9 versus 16.1 pack-years). There was also evidence of premorbid personality differences between probands and co-twins dating back to late adolescence or early adult years. These preliminary findings suggest that genetic factors do not play a major role in the etiology of Parkinson disease and point to a prodromal onset of the disease as early as late adolescence or early adult life.

Neurology . 1981 Jan;31(1):77-80

Effect of deprenyl on the progression of disability in early Parkinson's disease. The Parkinson Study Group.
In a clinical trial that is still in progress, we studied the ability of deprenyl and tocopherol, antioxidative agents that act through complementary mechanisms, to delay the onset of disability necessitating levodopa therapy (the primary end point) in patients with early, untreated Parkinson's disease. Eight hundred subjects were randomly assigned in a two-by-two factorial design to receive deprenyl, tocopherol, a combination of both drugs, or placebo, and were followed up to determine the frequency of development of the end point. The interim results of independent monitoring prompted a preliminary comparison of the 401 subjects assigned to tocopherol or placebo with the 399 subjects assigned to deprenyl, alone or with tocopherol. Only 97 subjects who received deprenyl reached the end point during an average 12 months of follow-up, as compared with 176 subjects who did not receive deprenyl (P less than 10(-8). The risk of reaching the end point was reduced by 57% for the subjects who received deprenyl (Cox hazard ratio, 0.43; 95% confidence limits, 0.33 and 0.55; P less than 10(-10]. The subjects who received deprenyl also had a significant reduction in their risk of having to give up full-time employment (P = 0.01). We conclude from these preliminary results that the use of deprenyl (10 mg per day) delays the onset of disability associated with early, otherwise untreated cases of Parkinson's disease.

N Engl J Med. 1989 Nov 16;321(20):1364-71

Ropinirole for the treatment of early Parkinson's disease. The Ropinirole Study Group.
A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.

Neurology . 1997 Aug;49(2):393-9

Smoking, alcohol, and coffee consumption preceding Parkinson's disease: a case-control study.
OBJECTIVE: To study the association of PD with preceding smoking, alcohol, and coffee consumption using a case-control design. METHODS: The authors used the medical records linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County , MN , during the years 1976 to 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control subject. The authors reviewed the complete medical records of cases and control subjects to abstract exposure information. RESULTS: For coffee consumption, the authors found an OR of 0.35 (95% CI = 0.16 to 0.78, p = 0.01), a dose-effect trend (p = 0.003), and a later age at PD onset in cases who drank coffee compared with those who never did (median 72 versus 64 years; p = 0.0002). The inverse association with coffee remained significant after adjustment for education, smoking, and alcohol drinking and was restricted to PD cases with onset at age <72 years and to men. The OR for cigarette smoking was 0.69 (95% CI = 0.45 to 1.08, p = 0.1). The authors found no association between PD and alcohol consumption. Extreme or unusual behaviors such as tobacco chewing or snuff use and a diagnosis of alcoholism were significantly more common in control subjects than cases. CONCLUSIONS: These findings suggest an inverse association between coffee drinking and PD; however, this association does not imply that coffee has a direct protective effect against PD. Alternative explanations for the association should be considered.

Neurology. 2000 Nov 14;55(9):1350-8

Diet and Parkinson's disease. II: A possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case-control study.
In a case-control study, we compared the past dietary habits of 342 Parkinson's disease (PD) patients recruited from nine German clinics with those of 342 controls from the same neighborhood or region. Data were gathered with a structured interview and a self-administered food-frequency questionnaire. Nutrient intakes were calculated from the reported food intakes through linkage with the German Federal Food Code and analyzed using multivariate conditional logistic regression to control for total energy intake, educational status, and cigarette smoking. At the macronutrient level, patients reported higher carbohydrate intake than controls after adjustment for total energy intake, smoking, and educational status (OR = 2.74, 95% confidence interval [CI]: 1.30-6.07, for the highest versus lowest quartile, p trend = 0.02). This was reflected in higher monosaccharide and disaccharide intakes at the nutrient level. There was no difference between patients and controls in protein and fat intake after adjustment for energy intake. We found an inverse association between the intakes of beta-carotene (OR = 0.67, 95% CI: 0.37-1.19, p trend = 0.06) and ascorbic acid (OR = 0.60, 95% CI: 0.33-1.09, p trend = 0.04) by patients, although only the trend for ascorbic acid intake reached statistical significance. There was no difference between groups for alpha-tocopherol intake after adjustment for energy intake. We also found that patients reported a significantly lower intake of niacin than controls (OR = 0.15, 95% CI: 0.07-0.33, p trend < 0.00005). Our results suggest that if antioxidants play a protective role in this disease, the amounts provided by diet alone are insufficient. Although the interpretation of the inverse association between niacin intake and PD is complicated by the high niacin content in coffee and alcoholic beverages, which were also inversely associated with PD in this study, the strength of this association and its biologic plausibility warrant further investigation.

Neurology . 1996 Sep;47(3):644-50