Cand.psychol. Bjørn-Eivind Seljelid Bordewick Kirsebom disputerer for ph.d.-graden i helsevitenskap og vil offentlig forsvare avhandlingen:
“Dementia Disease Initiation: Identifying subjective cognitive decline (SCD) due to Alzheimer’s disease”
Kort sammendrag av avhandlingen:
Alzheimer’s disease is the leading cause of dementia and comprising between 50-75 % of cases. The biological underpinnings of Alzheimer’s disease may begin 10 – 15 years before the disease manifests as objective deficits in cognition. Discovering disease markers at this early preclinical stage will increase our understanding of early disease mechanisms and hopefully lead to the development of interventions that can prevent, halt or stop disease progression. Succeeding in this task would be of enormous benefit to patients, caregivers and society as a whole. The experience of subjective cognitive decline is a known risk factor for Alzheimer’s disease development. However, most cases are indeed benign and a part of normal aging. This thesis aimed to investigate the role of subjective cognitive decline as a preclinical stage of Alzheimer’s disease.
We sought to improve early detection of at-risk individuals by investigating potential biases in participant recruitment methods, improve tools for assessment of memory performance, and investigate a new cerebrospinal fluid biomarker, the neurogranin/BACE1 ratio, which may be tied to synapse loss in Alzheimer’s disease. Synapses are the primary connections between nerve cells, and loss of these connections lead to cognitive decline. The experience of subjective cognitive decline in patients with Alzheimer’s disease could be due to early loss of synapses that have yet to reach the threshold for objective cognitive deficits and present a possibility for early intervention.
We found that patients recruited from memory clinics, may be at higher risk of Alzheimer’s disease compared to volunteer participants from the community. This may be due to increased worry tied to subjective cognitive decline, or concerns voiced from their caregivers prompting patients to seek medical help. Our findings have important implications for participant recruitment, especially when recruiting at-risk individuals for medical intervention trials. Importantly, this may have implications for general practitioners seeing worried, but cognitive healthy patients with subjective cognitive decline. Memory performance is a central part of Alzheimer’s disease research. In this thesis, we developed more sensitive and culturally adapted test norms for a much used test of verbal memory performance. This will lead to a more accurate assessment of verbal memory performance in the clinic, and help clinicians determine normal from abnormal memory performance. Our research confirmed that the neurogranin/BACE1 ratio may indeed be a promising marker for synapse loss due to Alzheimer’s disease even at the preclinical phase of the disease. Our findings suggest that increased levels of this marker predict future cognitive decline and may point to the loss synapses as an early disease event. This finding could open possibilities for interventions aimed at preventing early synapse loss. Such future intervention could slow the progress of cognitive decline due to Alzheimer’s disease.
Veiledere
Hovedveileder professor Knut Waterloo
Biveileder førsteamanuensis Stein Harald Johnsen
Bedømmelseskomiteen
Professor Clive Ballard, The University of Exter Medical School, UK – 1. opponent
Professor Anders Martin Fjell, UiO – 2. opponent
Førsteamanuensis Matthias Mittner, UiT Norges arktiske universitet – leder av komité
Disputasleder Prodekan Jan Rosenvinge, Institutt for psykologi, Det helsevitenskapelige fakultet, Universitetet i Tromsø – Norges arktiske universitet
Prøveforelesning over oppgitt emne holdes kl. 11.15, samme sted: “The role of cognitive testing in Alzheimer's Disease: clinical and research perspectives”