The Environmental Epidemiology of Amyotrophic Lateral Sclerosis in Europe
Citation:
ROONEY, JAMES PATRICK, The Environmental Epidemiology of Amyotrophic Lateral Sclerosis in Europe, Trinity College Dublin.School of Medicine.CLINICAL MEDICINE, 2018Download Item:
Thesis_FINAL_27SEP2018_nofields.pdf (PDF) 25.20Mb
Abstract:
Amyotrophic Lateral Sclerosis (ALS) is a terminal neuro-degenerative disorder of
adults, typically having rapid progression and involving both motor and cognitive
function. ALS exhibits considerable heterogeneity of both symptom profile and
progression. Nevertheless, median survival is typically under three years from
disease onset. ALS is the most common motor neurone disease in adults, with an
incidence of 2 to 3 per 100,000 in Europe. The cause of ALS is unknown, however
current expert opinion is that the disease occurs as a result of the combined
effects of genetic and environmental factors.
The primary aims of this thesis were to investigate environmental exposures as
risk factors for ALS in Irish and European populations, and to investigate clinical
and genetic prognostic factors in those populations. Data was obtained using the
Irish ALS Register, and from Euro-MOTOR - an international, case-control study of
Dutch, Irish and Italian ALS patients matched healthy controls.
Overall, the findings from this thesis provide evidence that occupational and
environmental exposures have importance in ALS aetiology. Spatial
epidemiological analysis of the Irish ALS cohort found two significant areas of low
risk for ALS, and the Euro-MOTOR study revealed associations between oral
contraceptive pill use, physical activity, occupational exposures and ALS risk. These
findings indicate the need for large gene-environment studies in future ALS
research. Furthermore, survival analyses reinforced previous evidence that
attendance at an ALS multidisciplinary clinic is associated with improved survival,
and provided fresh insight into the prognostic effect of the C9orf72 expansion in
ALS, indicating that stratification by C9orf72 expansion status is important in
epidemiological studies. Finally, longitudinal and prognostic characteristic of subscores
of the ALS Functional Rating Scale (ALSFRS) were explored and were found
to be independently associated with survival. This may help to inform future
clinical trial design.
Sponsor
Grant Number
Grant number: HPF-2014-527
Health Research Board (HRB)
Author's Homepage:
http://people.tcd.ie/rooneyj5Description:
APPROVED
Author: ROONEY, JAMES PATRICK
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Trinity College Dublin. School of Medicine. Discipline of Clinical MedicineType of material:
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