New thesis on factors that influence ALS risk and prognosis
Welcome to Charilaos Chourpiliadis' presentation of his thesis ”A novel evaluation of potential risk and prognostic factors for amyotrophic lateral sclerosis”.
Time: February 13 at 9.00
Location: Eva George Klein, Biomedicum + Online
Supervisor: Professor Fang Fang, Karolinska Institutet, Institute of Environmental Medicine
Opponent: Dr. Bryan Traynor, National Institute of Aging, Laboratory of Neurogenetics
Three questions to Charilaos Chourpiliadis
What is the thesis about?
Leveraging data from Swedish national and quality registers, we explored how cardiometabolic conditions, lifestyle factors, mental health and trace metals influence both the risk of developing ALS and the progression after diagnosis.
Can you tell us about some interesting results?
People who later developed ALS were less likely to have been diagnosed years earlier with type 2 diabetes or high cholesterol. At the same time, once ALS was diagnosed, individuals who had heart and blood vessel conditions tended to experience faster disease progression and shorter survival. We also identified distinct subgroups of ALS patients: those who were older, had poorer physical function at diagnosis, and had more cardiometabolic diseases fared the worst over time.
A higher long-term BMI over adulthood was consistently linked to a lower risk of developing ALS, and among patients, a higher BMI was associated with better survival. In contrast, smoking—particularly heavy smoking—was strongly linked to poorer outcomes after diagnosis.
Mental health emerged as another important factor. People who had previously used common psychiatric medications, such as antidepressants or anti-anxiety drugs, had a higher likelihood of being diagnosed with ALS later in life, and among ALS patients, to have a worse prognosis. These findings suggest that mental health symptoms may be part of the early disease process or reflect shared biological pathways with ALS.
Finally, we examined metal levels in hair samples. Although higher levels of these metal mixtures were not clearly linked to poorer survival, they may be linked to disease susceptibility, especially in genetically vulnerable individuals.
What further research is needed in the area?
ALS represents a constellation of different clinical phenotypes. Clustering patients in relation to these phenotypes as well as genetic, environmental, radiologic, and emerging multi-omic factors (e.g., microbiome and proteomics) could more effectively address disease heterogeneity and may help identify specific pathophysiological “signals” underlying distinct ALS subtypes.