Analysis of Physical Activity as an Environmental Risk Factor for Motor Neurone Disease (MND)

Lead Research Organisation: University of Sheffield
Department Name: Biomedical Science


In motor neurone disease (MND), damage to the nervous system causes progressive limb weakness and difficulty with speech, swallowing and ultimately breathing. The cause of MND is unknown and there are no effective treatments. Sadly, patients with MND usually die within 3 years of symptom onset.

Interest in physical activity (PA) as a risk factor for MND arose from suggestions that professional sports people may develop MND more often than is expected. Therefore, we plan to perform a study to investigate if MND patients are more likely to have undertaken high levels of PA in the past compared to healthy volunteers. We propose to interview patients and volunteers using a questionnaire we have designed which measures the PA performed throughout a personā€˜s adult life. We will analyse the data collected to determine if an association does exist.

We hypothesise that PA is a risk factor for MND in only a proportion of genetically susceptible individuals and by determining this association we will gain insight into this abnormal biological response to PA. We hope the results will ultimately contribute to the development of new MND treatments by improving our understanding of the environmental and genetic interacting factors associated with this disease.

Technical Summary

Recent reports suggesting a higher incidence of motor neurone disease (MND) in professional sports people have led to speculation of an aetiological relationship between intense physical activity (PA) and the development of MND. This is supported by hypotheses regarding the underlying pathogenesis of MND, in particular oxidative stress and glutamate excitotoxicity. However, definitive evidence of such an association is lacking, with prior studies plagued by methodological problems and conflicting results.

Aims and Objectives
We hypothesise that participation in a high level of PA is associated with an increased risk of developing MND in individuals with underlying genetic susceptibility. Our objectives are to produce and validate a novel adulthood PA questionnaire and to use this questionnaire to retrospectively evaluate PA as a risk factor for MND.

In collaboration with the MRC Epidemiology Unit, a novel historical PA questionnaire has been designed. This interview-administered questionnaire collects data regarding adulthood PA at home, work and during recreation, using closed questions structured into discrete time periods. Validation of the questionnaire against objective PA measurements collected at two points of time in the past has been conducted, using participants from an established population-based cohort assembled by the Epidemiology Unit in 1990. Statistical analysis has demonstrated that questionnaire-derived PA data correlates significantly with the objective PA measurements.

The validated questionnaire will be used in a retrospective case control study to determine any association between MND and PA. 364 incident cases with definite or probable disease will be recruited from MND centres in the Yorkshire region, with 728 matched community controls identified through local Primary Care Trust patient databases. Cases and controls will be blinded to the study hypothesis. PA data collected by the questionnaire will be quantified using an established coding scheme for energy expenditure during PA. Statistical methods will be used to compare PA patterns between cases and controls and determine any association between PA and MND.

Scientific and Medical Opportunities
The challenge to find effective disease-modifying therapies for MND would be greatly enhanced by clearer elucidation of pathoaetiological mechanisms involved. Identifying exogenous risk factors in MND will provide guidance for future laboratory-based research. This study will also support further analysis of participants to determine genetic variations which convey MND susceptibility and may also interact with the effects of PA. A valid tool for assessing adulthood PA is likely to have widespread applications as interest in the health consequences of lifestyle behaviours escalates.


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