Elsevier

The Lancet Neurology

Volume 5, Issue 6, June 2006, Pages 525-535
The Lancet Neurology

Review
Epidemiology of Parkinson's disease

https://doi.org/10.1016/S1474-4422(06)70471-9Get rights and content

Summary

The causes of Parkinson's disease (PD), the second most common neurodegenerative disorder, are still largely unknown. Current thinking is that major gene mutations cause only a small proportion of all cases and that in most cases, non-genetic factors play a part, probably in interaction with susceptibility genes. Numerous epidemiological studies have been done to identify such non-genetic risk factors, but most were small and methodologically limited. Larger, well-designed prospective cohort studies have only recently reached a stage at which they have enough incident patients and person-years of follow-up to investigate possible risk factors and their interactions. In this article, we review what is known about the prevalence, incidence, risk factors, and prognosis of PD from epidemiological studies.

Introduction

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease and is expected to impose an increasing social and economic burden on societies as populations age. In recent years, the interest of the scientific community in PD has grown substantially, triggered by the discovery of several causative monogenetic mutations. However, these mutations likely only explain a small proportion of all PD and about 90% of cases are apparently sporadic. Despite insights derived from genetic research, the exact pathogenetic mechanisms underlying the selective dopaminergic cell loss in PD are still not understood. Current thinking is that mitochondrial dysfunction, oxidative stress, and protein mishandling have a central role in PD pathogenesis,1 and that in sporadic PD these processes are induced by non-genetic factors, probably in interaction with susceptibility genes. Insight in non-genetic causes is needed to further the understanding of the pathogenesis of the disease and to develop effective therapeutic strategies. Large, well-designed, prospective population-based cohort studies are the only studies suited to examine the effects of multiple potential risk factors and their interactions, as well as effects that develop over a longer period.

In the past, numerous methodologically limited epidemiological studies on PD have been done, mostly small case-control or register-based studies, many based on prevalence. Only in the past 5–7 years have larger prospective studies reached a stage where they have identified sufficient numbers of patients with PD to examine incidence and potential risk factors of the disease. In this article, we will review what is known about the prevalence, incidence, risk factors, and prognosis of PD from epidemiological studies. Special attention will be given to methodological issues, as the usefulness of epidemiological data and interpretation of findings are largely dependent on the quality of the studies they were obtained from.

Section snippets

Diagnosis of PD in epidemiological research

A reliable and easily applicable diagnostic test or marker for PD is not yet available. Sophisticated imaging with single-photon-emission CT or PET may be helpful to diagnose PD in specialised settings, but although these techniques have become more widely available and easier to use, their usefulness for population-based epidemiological research is still limited. Thus, a diagnosis of PD in epidemiological studies is primarily based on clinical symptoms. Current criteria for a diagnosis of

Methodological considerations

Estimates of the prevalence and incidence of PD may vary according to applied methodology, which complicates comparison across studies.3, 4, 5 Not surprisingly, the use of stricter diagnostic criteria yields lower estimates of prevalences and incidence.3 Estimates are influenced even more by case-finding strategies. Record-based studies and studies done in clinical settings do not include patients who have not sought medical attention, and thus underestimate the prevalence or incidence of PD in

Methodological considerations

Many environmental risk factors for PD have been proposed on the basis of presumed pathogenetic mechanisms of the disease. Most of these risk factors were examined in retrospective case-control studies, which are prone to several kinds of bias, especially recall bias, selection of inappropriate controls, or inaccurate ascertainment of PD resulting in selected case series. An important caveat in the interpretation of case-control studies is reversed causality, which may particularly play a part

Causative genes

Monogenetic causes do not seem to have a primary role in most cases of PD. Although in several studies a positive family history has been associated with a high risk of PD, in most cases a clear mode of inheritance could not be established.87 A significant effect of genetic factors was found in a study among almost 20 000 male twins, but predominantly in PD with onset before age 50 years.88 Since 1997, several families have been identified with parkinsonism with clear mendelian inheritance, and

Methodological considerations

Several studies investigated the life expectancy and occurrence of dementia in patients with PD. Most of these studies were done in patient groups from specialised centres or used medical records to find cases. Patients with relatively mild symptoms are likely to be under-represented in these studies and results therefore are not representative of the general population. Besides, many of these studies did not account for duration of disease at the time of enrolment. Population-based cohorts

Conclusions

PD is a common disease, especially beyond age 60 years. In sporadic cases, the causes and aetiology are still largely unknown. For most of the factors, evidence is still inconclusive and, thus far, older age and smoking habits are the only risk factors for PD that have consistently been found across studies. Many of the initial studies on the epidemiology of PD were too small or had methodological limitations that hampered the interpretability of their findings. The paucity of well-designed and

Search strategy and selection criteria

References for this review were identified by searches of MEDLINE and PubMed and from the reference lists of relevant papers. The search terms used were “Parkinson disease”, “PD”, “parkinsonism”, “epidemiology”, “cohort study”, “prevalence”, “incidence”, “risk factors”, “pesticide”, “diet”, “coffee”, “smoking”, “alcohol”, “estrogen”, “inflammation”, “cancer”, “susceptibility genes”, “mortality”, “dementia”, and “prognosis”. Only papers published in English between 1969 and February 2006

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