A systematic review on the risk of neurodegenerative diseases and neurocognitive disorders in professional and varsity athletes.

OBJECTIVE: The aim of this systematic review (SR) was to gather all available epidemiological evidence on former participation in any type of sport, at a professional and varsity level, as a potential risk factor for neurodegenerative diseases (NDs) and neurocognitive disorders (NCDs). DESIGN: Systematic searches were performed on PubMed, the Cochrane databases, and the ISI Web of Knowledge databases. Included studies were assessed using the NOS checklist. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: All epidemiological studies reporting data on the possible association between a clinical diagnosis of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND), dementia or mild cognitive impairment (MCI), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE) at any stage and with any clinical pattern and the former participation in any types of sport at a varsity and professional level were included. RESULTS: Data from the 17 included studies showed a higher frequency of NDs and NCDs in former soccer and American football players. Updating the previous SR confirmed a higher frequency of ALS/MND in former soccer players. Data reported a significantly higher risk of dementia/AD in former soccer players, and of MCI in former American football players. Results also showed a significantly higher risk of PD in former soccer and American football players, and a significantly higher risk of CTE in former boxers and American football players. This SR confirmed a higher risk of NDs and NCDs in former professional/varsity athletes. However, the pathological mechanisms underlying this association remain unclear, and further high-quality studies should be performed to clarify whether the association could be sport specific.

Trauma and amyotrophic lateral sclerosis: a case-control study from a population-based registry.

BACKGROUND AND PURPOSE: Published reports on the association between amyotrophic lateral sclerosis (ALS) and trauma are controversial suggesting the need for a new case-control study done in a large population. METHODS: A case-control study was undertaken in Italy to assess this association. Cases were patients with newly diagnosed ALS from four population-based registries. For each case, two hospital controls were selected, matched for age, sex, and province of residence, one with a neurological (non-degenerative) disease and one with a non-neurological disease (other than orthopedic or surgical). Traumatic events (defined as accidental events causing injuries requiring medical care) were recorded with details on type, site, timing, severity, and complications. The risks were assessed as odds ratios (ORs) with 95% confidence intervals (CI), crude and adjusted for age, sex, education, interviewee (patient or surrogate), physical activity, smoking, alcohol, and coffee. RESULTS: The study population comprised 377 patients in each of the three groups. One or more traumatic events were reported by 225 cases (59.7%), 191 neurological controls (50.7%), and 179 non-neurological controls (47.5%) (P < 0.01) (OR 1.63; 95% CI 1.25-2.14) (P < 0.01). The ORs were 3.07 (95% CI 1.86-5.05) for patients reporting 3+ traumatic events and 2.44 (95% CI 1.36-4.40) for severe traumatic events. The ORs remained significant when the analysis was limited to events that occurred 5+ and 10+ years before ALS onset, to incident ALS, and direct informant. CONCLUSION: Antecedent trauma, repeated trauma, and severe trauma may be risk factors for ALS.

Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial.

BACKGROUND: A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported. We performed a multicenter trial with lithium carbonate to assess its tolerability, safety, and efficacy in patients with ALS, comparing 2 different target blood levels (0.4-0.8 mEq/L, therapeutic group [TG], vs 0.2-0.4 mEq/L, subtherapeutic group [STG]). METHODS: The study was a multicenter, single-blind, randomized, dose-finding trial, conducted from May 2008 to November 2009 in 21 Italian ALS centers. The trial was registered with the public database of the Italian Agency for Drugs (http://oss-sper-clin.agenziafarmaco.it/) (EudraCT number 2008-001094-15). RESULTS: As of October 2009, a total of 171 patients had been enrolled, 87 randomized to the TG and 84 to the STG. The interim data analysis, performed per protocol, showed that 117 patients (68.4%) discontinued the study because of death/tracheotomy/severe disability, adverse events (AEs)/serious AEs (SAEs), or lack of efficacy. The Data Monitoring Committee recommended stopping the trial on November 2, 2009. CONCLUSIONS: Lithium was not well-tolerated in this cohort of patients with ALS, even at subtherapeutic doses. The 2 doses were equivalent in terms of survival/severe disability and functional data. The relatively high frequency of AEs/SAEs and the reduced tolerability of lithium raised serious doubts about its safety in ALS. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that therapeutic (0.4-0.8 mEq/L) vs subtherapeutic (0.2-0.4 mEq/L) lithium carbonate did not differ in the primary outcome of efficacy (survival/loss of autonomy) in ALS. Both target levels led to dropouts in more than 30% of participants due to patient-perceived lack of efficacy and AEs.