Family history of neurodegenerative and vascular diseases in ALS: a population-based study

To determine whether the frequency of Parkinson disease (PD), dementia, and vascular diseases in relatives of patients with amyotrophic lateral sclerosis (ALS) differs from the frequency of those diseases in relatives of controls, providing further information about the association between these diseases.

We studied the occurrence of neurodegenerative and vascular diseases in families of patients with ALS in a prospective, population-based, case-control study in the Netherlands between 2006 and 2009, using the recurrence risk λ. Family history data were obtained by asking participants to fill in questionnaires.

A total of 635 patients and 1,616 controls were included. The frequency of dementia was mildly increased only among parents and siblings of patients with sporadic ALS (λ1.32; 95 confidence interval [CI] 1.10-1.59), not among grandparents, or aunts and uncles. The risk of PD was not elevated (any relative: λ 0.91; 95% CI 0.70-1.17). Among relatives of patients with familial ALS, no significantly increased risk of neurodegenerative diseases was found. A reduced risk of vascular diseases was found in relatives of patients with sporadic ALS (stroke: λ 0.90; 95% CI 0.80-1.01 and myocardial infarction: λ 0.86; 95% CI 0.79-0.94), and in relatives of patients with familial ALS (stroke: λ 0.88; 95% CI 0.61-1.27 and myocardial infarction: λ 0.61; 95% CI 0.43-0.86).

This large, prospective, population-based study showed that familial aggregation of ALS, dementia, and PD is substantially lower than previously thought. The lowered risk of vascular diseases in relatives of patients with ALS supports the view that a beneficial vascular risk profile increases ALS susceptibility.