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To date, the role of blood lipid levels and their association with the onset and prognosis of ALS is controversial. We explored these associations in a large, population-based case-control study.Between October 2010 and June 2014, 336 ALS patients (mean age 65.7 ± 10.7; 57.7% male) and 487 sex- and age-matched controls from the same geographic region were recruited within the ALS registry in Southwest Germany. Triglycerides and cholesterol (high-density lipoprotein (HDL), low-density lipoprotein (LDL), total) were measured. The ALS cohort was followed up for vital status. Conditional logistic regression models were applied to calculate odds ratio (OR) for risk of ALS associated with serum lipid concentrations. In ALS patients only, survival models were used to appraise the prognostic value.High concentration of total cholesterol (OR 1.60, 95% confidence interval (CI) 1.03-2.49, top vs. bottom quartile), but not HDL, LDL, LDL-HDL ratio, or triglycerides, was positively associated with the risk of ALS. During the median follow-up time of 88.9 months, 291 deaths occurred among 336 ALS patients. In the adjusted survival analysis, higher HDL (HR 1.72, 95% CI 1.19-2.50) and LDL cholesterol levels (HR 1.58, 95% CI 1.11-2.26) were associated with higher mortality in ALS patients. In contrast, higher triglyceride levels were associated with lower mortality (HR 0.68, 95% CI 0.48-0.96).The results highlight the importance to distinguish cholesterol from triglycerides when considering the prognostic role of lipid metabolism in ALS. It further strengthens the rationale for a triglyceride-rich diet, while the negative impact of cholesterol must be further explored.

Background and ObjectivesWhether physical activity (PA) is a risk factor for amyotrophic lateral sclerosis (ALS) is controversial because data on lifelong PA are rare. The main objective of this study is to provide insight into PA as a potential risk factor for ALS, reporting data on cumulative PA, leisure-time PA, and occupational PA. This study also aims to gather evidence on the role of PA as a prognostic factor in disease course.MethodsLifetime PA values collected by questionnaires addressing work and leisure time were quantified into metabolic equivalents (METs). A population-based case-control study embedded in the ALS Registry Swabia served to calculate the odds ratio (OR) of ALS by PA in different time intervals and prognosis.ResultsIn ALS cases (393 cases, 791 age- and sex-matched controls), we observed reduced total PA at interview and up to 5 years before interview compared to controls. Total PA was not associated with ALS risk 5 to 55 years before interview. Heavy occupational work intensity was associated with increased ALS risk (OR 1.97, 95% confidence interval 1.34, 2.89). Total PA levels were associated with survival in a nonlinear manner: inactive patients and highest activity levels (25 MET-h/wk) revealed the worst survival time of 15.4 and 19.3 months, respectively. Best median survival with 29.8 months was seen at 10.5 MET-h/wk after adjustment for other prognostic factors.DiscussionLifetime combined PA decreased sharply several years before disease onset compared to controls. The risk of developing ALS was not associated with former total PA levels 5 to 55 years before interview in contrast to occupational PA, probably reflecting work-associated exposures. We found a strong nonlinear association of current and prediagnostic PA level and survival in ALS cases with the best survival with moderate PA. PA intensity may be a disease-modifying factor with an unfavorable outcome in sedentary and hyperactive behavior.Classification of EvidenceThis study provides Class III evidence that PA was not associated with the development of ALS.