Mortality among family members of patients with amyotrophic lateral sclerosis – a Swedish register-based study

Abstract

Objective: To test two hypotheses: (1) partners of ALS patients have higher mortality due to outcomes related to psychological distress, and (2) parents and siblings of ALS patients have higher mortality due to diseases that co-occur with ALS.

Methods: We performed a nationwide, register-based cohort study in Sweden. We included ALS-free partners, biological parents and full siblings (N = 11,704) of ALS patients, as well as ALS-free partners, biological parents and full siblings (N = 14,460,150) of ALS-free individuals, and followed them during 1961–2013. Hazard ratios (HRs) and 95% confidence intervals (CIs) of overall and cause-specific mortality were derived from Cox regression.

Results: Partners of ALS patients, compared to partners of ALS-free individuals, displayed higher mortality due to external causes (HR 2.14; 95% CI 1.35–3.41), including suicide (HR 2.44; 95% CI 1.09–5.44) and accidents (HR 2.09; 95% CI 1.12–3.90), after diagnosis of the ALS patients. Parents of ALS patients had a slightly higher overall mortality (HR 1.03; 95% CI 1.00–1.07), compared with parents of ALS-free individuals. This was driven by mortality due to dementias and cardiovascular, respiratory, and skin diseases. Parents of ALS patients had, however, lower mortality than parents of ALS-free individuals due to neoplasms. Siblings of ALS patients had higher mortality due to dementias, and digestive and skin diseases.

Conclusions: Increased mortality due to suicide and accidents among partners of ALS patients is likely attributable to severe psychological distress following the ALS diagnosis. Increased mortality due to dementias among parents and full siblings of ALS patients suggests shared mechanisms between neurodegenerative diseases.

Keywords:

• Amyotrophic lateral sclerosis
• family members
• mortality
• psychological distress
• register-based study

Disclosure statement

Henrik Larsson has served as a speaker for Evolan Pharma and Shire/Takeda, and has received research grants from Shire/Takeda; all outside the submitted work. Caroline Ingre serves as a member of the ALS Advisory Board EU for Biogen, a member of the Publication Steering Committee for Cytokinetics, a board member of the data monitoring committee of APL-ALS 206 for Apellis Pharmaceutical, a board member of the Stiching TRICALS Foundation; all outside the submitted work. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability statement

The data are not publicly available due to privacy or ethical restrictions.

Additional information

Funding

This study was partly supported by the Swedish Research Council [grant number: 2019-01088], the Karolinska Institutet (Senior Researcher Award and Strategic Research Area in Epidemiology), Bjorklunds Fund, Neuro Sweden, and the Ulla-Carin Lindquist Foundation. Caroline Ingre received grants from Pfizer; all outside the submitted work.