The doctoral dissertation in the field of Pharmacy will be examined at the Faculty of Health Sciences at Kuopio campus.
What is the topic of your doctoral research? Why is it important to study the topic?
Parkinson’s disease is a neurodegenerative disease the main symptoms of which include rigidity, tremor, and slowness of movements. The causes of Parkinson’s disease are often unknown and increasing age is the greatest risk factor. Currently, there is no cure or disease-modifying treatments. Over 6 million people are affected by Parkinson’s disease globally and due to population ageing the number is estimated to double by 2040. Some environmental factors have been identified to influence the risk of Parkinson’s disease, however, less is known about how other modifiable risk factors, such as drugs, are associated with the risk. Identifying drugs that are associated with a reduced risk of PD could aid in the discovery of new treatments for PD by elucidating molecular mechanisms that affect the development of PD. Risk factor studies are challenged by the long symptomatic period that precedes the diagnosis.
What are the key findings or observations of your doctoral research?
Study I investigated the incidence of muscle relaxant use in relation to Parkinson’s disease diagnosis as proxy for musculoskeletal symptoms. The use of muscle relaxants was more common among persons with Parkinson’s disease already three years before the diagnosis compared to persons without Parkinson’s disease. The findings from Study I helped to define an appropriate exposure assessment window for risk factor studies.
Study II investigated the association between disease-modifying antirheumatic drugs (DMARDs) and the risk of Parkinson’s disease among persons with rheumatoid arthritis. DMARDs were not associated with the risk of Parkinson’s disease except for chloroquine/hydroxychloroquine whose use at least three years before Parkinson’s disease diagnosis was associated with a reduced relative risk of Parkinson’s disease.
Study III investigated the association between inhaled beta-2 agonists and the risk of Parkinson’s disease among persons with asthma or chronic obstructive pulmonary disease. Inhaled beta-2 agonists were not associated with the risk of Parkinson’s disease and there was no clear dose-response relationship.
How can the results of your doctoral research be utilised in practice?
Describing the incidence of muscle relaxant use aided to select an appropriate drug exposure assessment window. This aims to control the potential reverse causality, that is a situation when a drug is seemingly a risk factor but the symptoms preceding the diagnosis have influenced the drug use. The findings call for careful examination of muscle symptoms among older persons due to their possible adverse effects.
Little is currently known about the association between DMARDs and the risk of Parkinson’s disease. This thesis provided novel information on how DMARDs are associated with the risk of Parkinson’s disease among persons with rheumatoid arthritis and paved the way for further investigations on the role of chloroquine and hydroxychloroquine.
According to findings from this thesis, inhaled beta-2 agonists do not seem to protect from Parkinson’s disease unlike some previous studies have suggested. Differences in study designs may explain the conflicting findings. Confounding factors were better accounted for by restricting Study III to persons with asthma or chronic obstructive pulmonary disease.
What are the key research methods and materials used in your doctoral research?
This thesis is based on the nationwide register-based Finnish Parkinson’s disease study (FINPARK) that includes community-dwelling persons that were diagnosed with Parkinson’s disease during 1996-2015 (N=22,189) and their matched comparison persons. All persons that received a special reimbursement for Parkinson’s disease drugs were identified from the Special Reimbursement Register after which those with potential misdiagnosis were excluded. Information on drug use was derived from the Finnish Prescription Register.
Study I was a cohort study, and Studies II-III were nested case-control studies, in which the drug exposure that had occurred at least three years before the index date was considered. The relative risk was estimated with conditional logistic regression and the model was adjusted with potential confounding factors. In Study III, the dose-response relationship was estimated by using defined daily dose.
The doctoral dissertation of Anne Paakinaho, MSc (Pharm), BSc (Biosciences) entitled Disease-modifying antirheumatic drugs and inhaled β2-adrenoceptor agonists and risk of Parkinson’s disease: a nationwide register-based study will be examined at the Faculty of Health Sciences at Kuopio campus. The Opponent in the public examination will be Professor Olaf Klungel of Utrecht University, and the Custos will be Professor Anna-Maija Tolppanen of the University of Eastern Finland.
For further information, please contact:
Anne Paakinaho, https://uefconnect.uef.fi/en/person/anne.paakinaho/
