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Karolinska Institute

1. Smailovic, Una. Multimodal phenotyping of synaptic damage in Alzheimer’s disease : translational perspective with focus on quantitative EEG .

Degree: 2020, Karolinska Institute

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Accumulation of AD-associated pathology in the brain may begin a decade or more before the appearance of the first symptoms of the disease. The pathological-clinical “continuum of AD” therefore encompasses time between the initial neuropathological changes and symptoms of advanced disease. Besides cognitively healthy individuals at risk, it includes subjects with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and eventually dementia when the severity of cognitive impairment affects patients’ ability to carry out everyday activities. Timely detection of the disease would therefore recognize patients that are at risk for future cognitive deterioration and provide time window for the prevention and novel therapeutical interventions. Accumulating evidence suggests that degeneration and dysfunction of brain neuronal connections, i.e. synapses, is one of the earliest and best proxies of cognitive deficits in patients along AD continuum. Human electroencephalography (EEG) is a non-invasive and widely available diagnostic method that records real-time large-scale synaptic activity. The commonly used method in research settings is quantitative EEG (qEEG) analysis that provides objective information on EEG recorded at the level of the scalp. Quantitative EEG analysis unravels complex EEG signal and adds relevant information on its spectral components (frequency domain), temporal dynamics (time domain) and topographic estimates (space domain) of brain cortical activity. The general aim of the present thesis was to characterize different aspects of synaptic degeneration in AD, with the focus on qEEG and its relationship to both conventional and novel synaptic markers. In study I, global qEEG measures of power and synchronization were found to correlate with conventional cerebrospinal fluid (CSF) biomarkers of Aβ and tau pathology in patients diagnosed with SCD, MCI and AD, linking the markers of AD pathology to the generalized EEG slowing and reduced brain connectivity in fast frequency bands. In study II, qEEG analysis in the time domain (EEG microstates) revealed alterations in the organization and dynamics of large-scale brain networks in memory clinic patients compared to healthy elderly controls. In study III, topographical qEEG analysis of brain functional connectivity was associated with regionspecific cortical glucose hypometabolism ([18F]Fluorodeoxyglucose positron-emission tomography) in MCI and AD patients. Study IV provided evidence that qEEG measures of global power and synchronization correlate with CSF levels of synaptic marker neurogranin, both modalities being in combination independent predictors of progression to AD dementia in MCI patients. Study V and associated preliminary study introduced in the thesis assessed the translational potential of CSF neurogranin and qEEG as well as their direct relationship to AD neuropathology in App knock-in mouse…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Smailovic, U. (2020). Multimodal phenotyping of synaptic damage in Alzheimer’s disease : translational perspective with focus on quantitative EEG . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/47419

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Smailovic, Una. “Multimodal phenotyping of synaptic damage in Alzheimer’s disease : translational perspective with focus on quantitative EEG .” 2020. Thesis, Karolinska Institute. Accessed January 16, 2021. http://hdl.handle.net/10616/47419.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Smailovic, Una. “Multimodal phenotyping of synaptic damage in Alzheimer’s disease : translational perspective with focus on quantitative EEG .” 2020. Web. 16 Jan 2021.

Vancouver:

Smailovic U. Multimodal phenotyping of synaptic damage in Alzheimer’s disease : translational perspective with focus on quantitative EEG . [Internet] [Thesis]. Karolinska Institute; 2020. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10616/47419.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Smailovic U. Multimodal phenotyping of synaptic damage in Alzheimer’s disease : translational perspective with focus on quantitative EEG . [Thesis]. Karolinska Institute; 2020. Available from: http://hdl.handle.net/10616/47419

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.