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Synaptic Molecular and Neurophysiological Markers Are Independent Predictors of Progression in Alzheimer's Disease
Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Huddinge, Sweden.
Jönköping University, School of Health and Welfare, HHJ, Institute of Gerontology. Jönköping University, School of Health and Welfare, HHJ. ARN-J (Aging Research Network - Jönköping).ORCID iD: 0000-0002-8617-0355
University of Bern, University Hospital of Psychiatry, Translational Research Center, Bern, Switzerland.
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
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2021 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 83, no 1, p. 355-366Article in journal (Refereed) Published
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Abstract [en]

Background: Cerebrospinal fluid (CSF) neurogranin and quantitative electroencephalography (qEEG) are potential molecular and functional markers of synaptic pathology in Alzheimer's disease (AD). Synaptic markers have emerged as candidate prognostic indicators of AD since synaptic degeneration was shown to be an early event and the best correlate of cognitive deficits in patients along the disease continuum. Objective: The present study investigated the association between CSF neurogranin and qEEG measures as well as their potential to predict clinical deterioration in mild cognitive impairment (MCI) patients. Methods: Patients diagnosed with MCI (n=99) underwent CSF conventional AD biomarkers and neurogranin analysis and resting-state EEG recordings. The study population was further stratified into stable (n=41) and progressive MCI (n=31), based on the progression to AD dementia during two years follow-up. qEEG analysis included computation of global field power and global field synchronization in four conventional frequency bands. Results: CSF neurogranin levels were associated with theta power and synchronization in the progressive MCI group. CSF neurogranin and qEEG measures were significant predictors of progression to AD dementia, independent of baseline amyloid status in MCI patients. A combination of CSF neurogranin with global EEG power in theta and global EEG synchronization in beta band exhibited the highest classification accuracy as compared to either of these markers alone. Conclusion: qEEG and CSF neurogranin are independent predictors of progression to AD dementia in MCI patients. Molecular and neurophysiological synaptic markers may have additive value in a multimodal diagnostic and prognostic approach to dementia.

Place, publisher, year, edition, pages
IOS Press, 2021. Vol. 83, no 1, p. 355-366
Keywords [en]
Alzheimer's disease, cerebrospinal fluid, mild cognitive impairment, neurogranin, prognostic markers, quantitative electroencephalography, synaptic markers
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:hj:diva-54613DOI: 10.3233/JAD-201234ISI: 000692658700029PubMedID: 34334389Scopus ID: 2-s2.0-85114397829Local ID: HOA;intsam;764811OAI: oai:DiVA.org:hj-54613DiVA, id: diva2:1593435
Funder
Gun och Bertil Stohnes StiftelseThe Swedish Brain Foundation, 2017-0243Torsten Söderbergs stiftelseSwedish Research Council, 2018-02843EU, Horizon 2020, 676144Alzheimerfonden, 742881Available from: 2021-09-13 Created: 2021-09-13 Last updated: 2021-09-23Bibliographically approved

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Kåreholt, Ingemar

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