Abstracts Category : Other

Metabolic disorders in the etiology of amyotrophic lateral sclerosis : an epidemiological approach

by Daniela Mariosa

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a loss ofmotor neurons in the brain and spinal cord, leading to progressive muscle weakness in multiple regionsof the body. No effective treatment is available and the disease progresses rapidly to death with anaverage survival time of 3-5 years after symptom onset. The etiology of ALS is unknown for the majorityof the patients. Alterations in the carbohydrate and lipid metabolisms, together with hypermetabolism,are features of ALS patients that are not yet well characterized. Understanding the early metabolicsymptoms of the disease might be a necessary step for the identification of an effective treatment. Paper I describes a nested case-control study on the association between diabetes and the futurerisk of ALS in the Swedish population. A total of 5,108 new ALS cases among the Swedish residentsbetween 1991 and 2010 were identified from the National Patient Register. Through linkages to severalnationwide Swedish registers five controls per case were selected from the entire Swedish populationusing incidence density sampling and diabetes diagnoses were identified for both cases and controlsfrom hospital admission records, outpatient care records, prescription of antidiabetics, or a combinationof the three. An overall inverse association between diabetes and risk of ALS was found. There washowever a positive association between insulin-dependent diabetes before age 30 and ALS risk. Paper II describes the association between body mass index (BMI), BMI change and ALS risk andsurvival in the GENEVA study, a case-control study of United States military veterans. Self-reportedBMI at age 25, 40 and at time of ALS diagnosis (interview for controls) was compared. Low BMI atage 40 was associated with increased risk of developing ALS and the association was stronger for caseswith diagnostic delay shorter than one year. Stable or decreasing BMI between age 25 and 40 was alsoassociated with higher risk of ALS compared to an increasing BMI. However, premorbid BMI and BMIchange did not predict survival of ALS patients. Paper III describes the association between ALS risk and serum glucose, total cholesterol, LDL-C,HDL-C, triglycerides, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I) in a Swedish populationbasedcohort study. High LDL-C, apoB and the LDL-C/HDL-C and apoB/apoA-I ratios were associatedwith a higher incidence of ALS. These associations seemed to be mainly due to a strong association ofapoB with ALS risk. High glucose level ( 6.11 mmol/L) was associated with a lower incidence of ALS.During the 10 years before diagnosis, ALS patients had increasing levels of LDL-C, HDL-C, apoB andapoA-I, whereas gradually decreasing levels of LDL-C/HDL-C and apoB/apoA-I ratios. Paper IV describes a population-based nested case-control study of 2,475 Swedish residents diagnosedwith ALS during July 2006-December 2013, and 12,375 population controls.