Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Michael Schöll, University of Gothenburg and University College London
- Second opponent: Associate Professor Torgil Vangberg, UiT Norges Arktiske Universitet, Norway
- Third member and chair of the evaluation committee: Professor II Anne Negård, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor Elisabeth Gulowsen Celius, University of Oslo
Principal Supervisor
Post doctor Per Selnes, Akershus universitetssykehus
Summary
Alzheimer’s disease (AD) is the most common cause of dementia. Deposition of amyloid-beta (Aβ) proteins into plaques is a pathological hallmark of AD (together with deposition of tau proteins), which can be detected by positron emission tomography (PET) computed tomography (CT) or measuring levels in cerebrospinal fluid (CSF). Unravelling early pathomechanistic events and biomarkers for early diagnosis are crucial for early intervention strategies, likely most effective in early disease before irreversible brain damage has occurred.
Compelling evidence suggests that cerebrovascular disease (CVD) and AD are closely related, and that white matter hyperintensities (WMHs), as markers of CVD, may be a core feature of AD. WMHs have been associated with markers of amyloid pathology and shown to increase several years before clinical symptoms. The aims of this thesis were to assess pathomechanistic associations between WMHs and AD by combining different neuroimaging entities and CSF biomarkers in patients with subjective cognitive decline or mild cognitive impairment.
The main findings were impaired microstructural integrity and more pronounced hypometabolism within WMHs, as assessed with diffusion tensor imaging and PET, respectively, in patients with amyloid pathology. They also investigated the use of amyloid PET in analyses of white matter pathology, but due to high aberrant uptake they could not conclude that the tracer is a suitable marker for white matter pathology.
In summary, they found further evidence for associations between WMHs and amyloid pathology. Amyloid-related vascular pathology may contribute to posterior WMHs and vascular risk factors may be involved in frontal regions. Detection of WMHs, especially posteriorly distributed, may thus potentially be a core feature in AD and aid in early diagnosis, which may also impact on treatment strategies.
Additional information
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