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Amyotrophic lateral sclerosis and parkinsonism-dementia on Guam: a 25-year prospective case-control study.

Familial and genetic studies of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia among the Chamorro people of Guam were initiated in 1958 with the establishment of a prospective case-control registry. The major objective of this registry was to determine if first-degree relatives and spouses of patients with amyotrophic lateral sclerosis or parkinsonism-dementia had an increased risk of developing disease compared with relatives of nonaffected controls individually matched for age, sex, and village. At the time of its closing in 1963, the registry included 126 patients (77 with amyotrophic lateral sclerosis, 42 with parkinsonism-dementia, and seven with both amyotrophic lateral sclerosis and parkinsonism-dementia) and an equal number of controls; 994 living first-degree relatives (parents, siblings, and offspring) of patients and 1,218 of controls; and 88 living spouses of patients and 101 of controls. The present analysis of the 25-year follow-up study (1958-1983) demonstrated a significantly increased risk of developing amyotrophic lateral sclerosis or parkinsonism-dementia among parents, siblings, and spouses of patients, but not among relatives of controls. Offspring of both patients and controls showed no significantly increased risk of developing disease. The increased risk among spouses of patients and the lack of increase among their offspring, together with recent histochemical findings, support the contention that exogenous factors are strong contributors to the etiology of amyotrophic lateral sclerosis and parkinsonism-dementia. The present results also demonstrate a declining incidence of both diseases.