Pre-symptomatic blood metal levels and the risk of ALS

Abstract

OPS 40: Metals: neurological effects, Room 412, Floor 4, August 28, 2019, 10:30 AM - 12:00 PM Background: Metals have been suggested as risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies on this possible association are available to date. We aimed to compare metal levels in prospectively collected blood samples from ALS patients and matched controls, to explore whether metals are associated with ALS risk. Methods: A nested case-control study for ALS was conducted within a large prospective European cohort. ALS cases were defined as those subjects for whom “motor neuron disease” was reported as an immediate, antecedent or underlying cause of death. We analysed erythrocytes metal levels in stored blood samples that were obtained at recruitment, as a biomarker for metal exposure from any source. Lead, mercury, manganese, selenium, copper, zinc, cadmium and arsenic concentrations were measured by sensitive and high-throughput methods, based on inductively coupled plasma-mass spectrometry. To estimate the risk of ALS in relation to pre-symptomatic blood metal levels, we applied conditional logistic regression models, adjusted for educational level, physical activity and smoking. Results: The study population comprised 107 cases (65% male) and 319 matched controls. The median age at recruitment was 60 and the median time between blood collection at recruitment and ALS death was 8 years (ranging from 1 to 15 years). Cadmium and lead levels were associated with increased ALS risk, but ORs attenuate after adjustment. Zinc levels were significantly associated with decreased ALS risk, but non-significant when adjusted. Conclusion: The metal concentrations in pre-symptomatic blood from ALS patients and controls indicated that cadmium and lead may be associated with an increased risk of ALS. This is the first study to compare metal levels before the disease onset, and hence avoiding any reverse causation, and our findings support previous suggestions that these metals play a role in the aetiology of ALS.