Tell us about your research!
Growing evidence points towards Alzheimer’s disease being more than just a neurocognitive disorder. Neuropsychiatric symptoms such as apathy, depression, anxiety, and irritability, are common for the patients to experience during at least some point of the disease course. My project focuses on elucidating the origin of apathy, anxiety, and depression in the early stages of the disease when the patients still haven’t developed dementia.
Accumulation of the proteins amyloid-beta and tau have for long been well-known pathological characteristics of Alzheimer’s disease. During my thesis work, I wanted to know whether early neuropsychiatric symptoms originate primarily from these pathological proteins or if other mechanisms are more likely to be in play. For this purpose, we used available samples and data from the already established BioFINDER study.
What is the most important finding you have made during your thesis work?
I discovered a link between increased amyloid-beta levels and the development of apathy and anxiety over time in initially cognitively normal older adults. The relationships were predominately independent from cognitive dysfunction. Hence, it seems likely that these symptoms are primarily driven by a direct effect of neuropathology, and do not arise as psychological reactions secondarily to a failing cognition.
Another interesting finding was that in cognitively healthy individuals with preclinical Alzheimer’s disease (abnormal levels of amyloid-beta in their cerebrospinal fluid), the overall burden of neuropsychiatric symptoms, but not episodic memory function, was associated with pathological tau levels. Normally we think of Alzheimer’s disease as an illness of lost memories; however, this finding points to neuropsychiatric symptoms as potentially earlier signs of certain Alzheimer’s pathologies than memory dysfunction.
Do you think that it may be possible to identify Alzheimer’s development earlier based on the presence of neuropsychiatric symptoms?
If I should be a bit visionary, it would be great if we could develop and implement a clinical protocol including neuropsychiatric symptoms as early indicators of Alzheimer’s disease before cognitive dysfunctions appear. Memory impairment might not be the first manifestation of disease in all patients, some might instead debut with e.g. anxiety.
Internationally, this is nothing new. Neuropsychiatric symptoms are already included in the NIA-AA research criteria for Alzheimer´s disease without any cognitive complaints requirements, but this only applies to the earliest stages of disease and is intended solely for scientific settings. The added value of these symptoms in diagnostic clinical criteria is still an under-investigated area where more knowledge is needed.
Neuropsychiatric symptoms constitute risk markers for future mild cognitive impairment or dementia. Moreover, according to some reports, around 25 % of all patients getting diagnosed with Alzheimer’s disease already have gotten a psychiatric diagnosis somewhat prior but yet adjacent to the final diagnosis of Alzheimer´s. Thus, including a standardized protocol for screening for prodromal Alzheimer’s disease in those with psychiatric symptoms above 60 years may be worth investigating.
Taken together, altering diagnostic criteria, or implementing clinical protocols, are of course long processes that require research efforts and thoughtful consideration. Still, I think it would be worth investing in projects that directly address the clinical utility of neuropsychiatric symptoms in Alzheimer´s disease.
How did you end up at MultiPark?
During my medical education, a close friend and I discussed the brain and different mental processes. Broadly, the mental processes can be divided into three main categories: cognitive, emotional, and motivational. Later, when starting to work as an assistant physician at the Clinical Unit for Cognitive Medicine in Ängelholm, I realized that emotional and motivational aspects of neurodegenerative diseases get little attention, but still they appear to be frequently present.
As I wanted to learn more about these non-cognitive mental abilities in detail, I headed on with a residency in clinical psychiatry. In parallel, I got in touch with Professor Oskar Hansson, who became my supervisor. As neuropsychiatric symptoms were not the research group's main focus, I am most grateful that he approved my stubbornness in studying these aspects of the disease. In the end, I found myself working in the perfect intersection between neurology and psychiatry.
What have you enjoyed the most during your research education at MultiPark?
To be honest, I haven’t participated that much since I work mainly from Ängelholm and Helsingborg. However, I am thankful to MultiPark for providing support with travel grants to attend conferences.
What have been the most challenging aspects of your Ph.D.?
The most demanding is to balance life with clinical duties, research and family life. It is peculiar that society is constructed in such a way that you expect to manage all these things simultaneously in your 30s. Professionally speaking, the statistical parts has been the most challenging to learn; how to design your project to go from your idea to the final analyses that are scientifically adequate and feasible at the same time. Fortunately, I have gotten a lot of help from my co-supervisor Niklas Mattsson-Carlgren, a great pedagogue when it comes to this.
And the most rewarding?
Standing at the edge of knowledge, trying to make qualified guesses about what is around the next corner, as well as planning for how the next step will be taken is highly satisfying.
What do you like to do when you are not at work?
Well, my biggest problem is prioritizing. There are so many fun things going on in life. To begin with, I have three children, which also places great demands on making qualified guesses about what is around the next corner, as well as planning ahead.
What advice do you want to give to new Ph.D. students?
The most important is to choose a subject which you find interesting. To do a PhD is a significant commitment; it is not worth it unless you are devoted to what you do. In other words, I would not recommend to undertake a PhD project only to get a PhD degree.
Another thing is to keep in mind that research is based upon being critical, which means that you should not take criticism and feedback personally. This is something you learn to handle during the process, and it is normal to have ups and downs on your way.
What happens after your defence?
I don’t exactly know. First, I will complete my remaining nine months of clinical residency in psychiatry. Then, I would like to continue with research based on my discoveries during the thesis work. It would be fun to dig even deeper into the chicken and the egg question concerning the link between neuropsychiatric symptoms, Alzheimer’s pathology, and cognitive dysfunctions. In other words, what comes first and what causes what? Also, addressing the clinical utility of neuropsychiatric symptoms would be meaningful but probably requires a new study (or cohort) to collect the relevant data.
