Parkinson's disease, smoking, and family history. EUROPARKINSON Study Group.

There is growing evidence that both genetic and environmental factors play a role in the etiology of Parkinson's disease (PD). The hypothesis of an interaction between genetic and environmental risk factors has been little explored, and never using a population-based case-control study design. Our objective was to investigate the possible interaction between smoking and family history in the etiology of PD, as part of a collaborative population-based case-control study. We included 149 nondemented PD patients ascertained in three European prevalence surveys using a two-phase design. Each patient was matched by age (+/-2 years), gender, and center to three controls drawn from the same populations (n=375). Presence of PD among first-degree relatives and smoking history were assessed through an interview for 127 cases and 306 controls. In the overall sample we found suggestive evidence that family history and ever-smoking interact in determining the risk of PD (P=0.09), with individuals exposed to both risk factors having the highest risk (OR=10.0; 95% CI=2.0-49.6). Analyses were repeated after stratification into two age-groups (cutoff: 75 years). In older patients, the joint exposure to both risk factors was associated with a significant increase in the risk of PD (OR=17.6; 95% CI=1.9-160.5). Among younger subjects, the OR for joint exposure was not significant. In conclusion, our findings suggest that smoking and family history interact synergistically on a multiplicative scale in determining the risk of PD in individuals older than 75 years.

Familial aggregation of Parkinson's disease: a population-based case-control study in Europe. EUROPARKINSON Study Group.

OBJECTIVE: To investigate the familial aggregation of PD in a large collaborative population-based case-control study. BACKGROUND: Most previous case-control studies of the familial aggregation of PD have been hospital- or clinic-based. METHODS: We included 219 prevalent cases ascertained in three European populations (centers), using a two-phase design consisting of screening and examination by a neurologist. Each case was matched by age, sex, and center to three controls drawn from the same populations (n = 657). Presence of PD among first-degree relatives (parents and siblings) was determined using the family history approach for 175 cases and 481 controls. RESULTS: Overall, a positive family history (at least one parent or sibling affected by PD) was reported in 10.3% of patients and 3.5% of controls (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.6 to 6.6). A similar association was observed when analyses were restricted to nondemented patients and controls (OR = 3.9; 95% CI = 1.7 to 8.7) or to newly diagnosed patients (OR = 3.3; 95% CI = 0.9 to 11.9). We found a significant trend of increasing risk with increasing number of affected relatives (p = 0.003). Analyses stratified by age showed a stronger association for younger PD patients (OR = 7.6; 95% CI = 1.5 to 38.9) than for older patients (OR = 2.5; 95% CI = 1.1 to 5.7). CONCLUSIONS: In this large sample of prevalent PD patients and population-matched controls, PD significantly aggregates in families, with the strength of the association being age-dependent. Therefore, familial factors, which can be genetic, environmental, or both, play a role in PD.

[New treatments in dementia]. / Nuevos tratamientos en demencia.

The advances in the treatment of Alzheimer's disease, mainly related to anticholinesterase drugs (tacrine, donepezil, metriphonate and rivastigmine) and the methodology of their application in clinical studies and in everyday neurologic practice are reviewed. Recent discoveries with the immunization with Abeta-42 of transgenic rats expressing a mutation related to Alzheimer's disease may lead to new possibilities of etiopathogenic treatments.

Smoking and Parkinson's disease. An age-dependent risk effect? The EUROPARKINSON Study Group.

We studied the association between smoking and Parkinson's disease (PD) through a case-control study. Several studies have shown an inverse association between smoking and PD. This association has been interpreted as spurious by some investigators, and as real and causal by others. Several other studies did not confirm the inverse association. We included 193 prevalent cases of PD ascertained in five European prevalence surveys that followed a two-phase design of screening and clinical examination. Each case was matched by center, age (+/- 2 years), and gender to three control subjects drawn from the same populations (N = 579). Information on smoking was obtained through direct or proxy interview. Overall, there was no association between ever smoking and PD (odds ratio = 1.1; p = 0.6). Analyses stratified by age showed that ever smoking was associated with a decreased risk of PD in the younger individuals (odds ratio = 0.4; p = 0.03) and with a significant trend of increasing risk with advancing age (p = 0.003). The risk of PD in relation to smoking is strongly modified by age; smoking may be protective in the younger cases but not in the older cases. This finding may explain the conflicting results from previous studies.

Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson's disease.

OBJECTIVES: To assess and compare the prevalence of parkinsonism and Parkinson's disease in five European populations that were surveyed with similar methodology and diagnostic criteria. METHODS: Joint analysis of five community surveys--Gironde (France), eight centres in Italy, Rotterdam (The Netherlands), Girona (Spain), and Pamplona (Spain)--in which subjects were screened in person for parkinsonism. Overall, these surveys comprised 14,636 participants aged 65 years or older. RESULTS: The overall prevalence (per 100 population), age adjusted to the 1991 European standard population, was 2.3 for parkinsonism and 1.6 for Parkinson's disease. The overall prevalence of parkinsonism for the age groups 65 to 69, 70 to 74, 75 to 79, 80 to 84, and 85 to 89 years was respectively, 0.9, 1.5, 3.7, 5.0, and 5.1. The corresponding age specific figures for Parkinson's disease were 0.6, 1.0, 2.7, 3.6, and 3.5. After adjusting for age and sex, the prevalence figures did not differ significantly across studies, except for the French study in which prevalence was lower. Prevalence was similar in men and women. Overall, 24% of the subjects with Parkinson's disease were newly detected through the surveys. CONCLUSIONS: Prevalence of both parkinsonism and Parkinson's disease increased with age, without significant differences between men and women. There was no convincing evidence for differences in prevalence across European countries. A substantial proportion of patients with Parkinson's disease went undetected in the general population.