The doctoral dissertation in the field of Pharmacoepidemiology will be examined at the Faculty of Health Sciences at Kuopio campus. The public examination will be streamed online.
What is the topic of your doctoral research? Why is it important to study the topic?
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with an escalating global prevalence. The incidence of AD and other dementias has increased by 148% over the 30-year period from 1990 to 2019. A significant proportion of individuals with Alzheimer’s disease also have concurrent cardiovascular diseases, as both AD and cardiovascular conditions share common risk factors. However, there are several challenges regarding the treatment of cardiovascular diseases within this population. Firstly, there are no clinical guidelines regarding cardiovascular drug use in people with AD. Secondly, people with AD are frequently excluded from randomized controlled trials due to their cognitive decline, psychotropic medications, and comorbidities. Therefore, real-world evidence utilizing register-based data could provide more representative insights into the treatment and medication usage in clinical practice.
What are the key findings or observations of your doctoral research?
The first study of this PhD research assessed the prevalence of cardiovascular drug use among persons with and without AD. The prevalence of cardiovascular drug use was comparable between the two cohorts at the time of AD diagnosis. However, a subsequent decrease in the prevalence of cardiovascular drug use was observed among persons with AD, while it remained constant among those without AD. The decrease in cardiovascular drug usage following Alzheimer's Disease (AD) diagnosis can be attributed to a variety of factors. Initially, the decline in cardiovascular risk factors, including blood pressure, body mass index, and cholesterol levels, is recognized to coincide with AD progression. This decline often accompanies frailty, malnutrition, and orthostatic hypotension. Consequently, the decrease in drug prescriptions may indicate a decreased necessity for treatment. Additionally, this trend may be attributed to shifting priorities among AD patients, opting for less aggressive care and transitioning from disease prevention to potentially palliative care or emphasizing quality of life.
The second study investigated the time to statin discontinuation and factors associated with statin discontinuation among persons with and without AD. Among statin discontinuers, although the risk of statin discontinuation was slightly higher in people with AD than those without AD, the absolute difference was minimal. The findings showed that cognitive decline slightly impacts the discontinuation of statins among older adults. Higher age and female gender were associated with an increased risk of discontinuation, whereas using other cardiovascular drugs and long duration of statin use before cohort entry were associated with lower risk in both cohorts.
The third study assessed the incidence of coronary artery revascularization after AD diagnosis and post-procedural outcomes, including mortality and readmissions between persons with and without AD. The finding was that the incidence rate of revascularization was lower in persons with AD than those without AD, and emergency procedures were more common among in AD population than among persons without AD. There were no differences in the 30-day readmission risk or one-year mortality, but persons with AD had a lower risk of readmission within 90 days. The 3-year mortality risk was higher in people with AD, but this observation was due to higher mortality in emergency procedures but not in electivity procedures. One explanation could be stricter criteria for elective procedures in people with AD than people without AD.
How can the results of your doctoral research be utilised in practice?
The studies I and II emphasize the need for regular assessment of medications with individual treatment aims and consideration of tapering cardiovascular drugs including statins in older population and especially in vulnerable population with AD.
The findings of the third study indicate that when revascularization is necessary for a person with AD, it appears more feasible to conduct the procedure in elective setting instead of postponing it to an emergency setting. However, the patient and caregiver preferences should be taken into account.
What are the key research methods and materials used in your doctoral research?
This thesis utilized data from a large, nationwide register-based Medication use in the Alzheimer’s Disease (MEDALZ) cohort. The MEDALZ cohort comprises 70,718 people residing in the community, clinically diagnosed with Alzheimer's Disease (AD) in Finland between 2005 and 2011. Each person in the AD cohort was matched with up to four individuals without AD based on age, sex, and region of residence. The data on AD diagnosis were extracted from the Special Reimbursement Register, and other information such as data on drug use, comorbidities, and outcomes was identified from the Prescription Register, the Care Register for Health Care, and the Causes of Death Register. Various programs were utilized to estimate the drug use periods such as PRE2DUP method in Study I and the AdhereR package in Study II. The association between AD, age, sex, and cardiovascular drug use was examined by generalized estimating equations logistic regression (Study I). Cox regression modes were applied to assess the factors associated with statin discontinuation (Study II) and outcomes including 30-day and 90-day hospital readmission and 1-year and 3-year mortality after revascularization (Study III).
The doctoral dissertation of Mai Vu, BPharm, MPH, entitled Cardiovascular drug utilization and postoperative outcomes of coronary artery revascularization procedures in people with Alzheimer’s disease, will be examined at the Faculty of Health Sciences at Kuopio campus. The Opponent in the public examination will be Professor Jenni Kulmala of Tampere University and the Custos will be Professor Anna-Maija Tolppanen of the University of Eastern Finland.
For further information, please contact:
Mai Vu, mai.vu(a)uef.fi
