Exogenous risk factors for amyotrophic lateral sclerosis

The aims of this thesis were to determine the epidemiology of ALS in the Netherlands, to determine the familial aggregation of ALS with Parkinson disease (PD), dementia, and vascular diseases, and to determine the association between several environmental and lifestyle factors and risk for sporadic ALS. We studied this in a population-based case-control study in the Netherlands, which is called the Prospective ALS study the Netherlands (PAN). The Netherlands provide ideal circumstances for a population-based study, since it is a densely populated country with 16.6 million inhabitants as of January 1, 2010 and an area of 41,528 km2, it has a well-developed infrastructure, and it has easy accessibility of health care to all inhabitants. Our study fulfilled the predefined criteria for a population-based case-control study to yield class I evidence on exogenous risk factors in sporadic ALS; i.e. a large number of newly diagnosed patients using multiple sources of cases ascertainment and with a diagnosis of ALS made applying established criteria, the use of randomly selected population-based and matched controls, high response rates, the use of detailed questionnaires accounting for exposure for disease onset, the quantification of exposures, the blinding of persons gathering the data on diseases status to ensure the uniform effort to gather information equally from affected and unaffected individuals, the blinding of participants and individuals gathering the data as to the hypotheses being tested, and the meticulous attention to avoid recall bias and confounding.