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Multimodal phenotyping of synaptic damage along the Alzheimer disease continuum
Author(s) -
Jelic Vesna
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044470
Subject(s) - neuroscience , neurodegeneration , dementia , context (archaeology) , ministate , electroencephalography , psychology , cognitive decline , cognition , medicine , disease , audiology , biology , paleontology
Background Dysfunction of brain neuronal connections is one of the earliest and best correlates of cognitive deficits in patients with Alzheimer disease (AD), preceding neuronal cell death. There is no established biomarker test for early synaptic pathology. In this context, EEG and novel CSF synaptic markers are of great interest as they complementarily mirror functional and molecular aspects of synaptic dysfunction. Method QEEG power, synchronisation, microstates and topographical analysis of generators of EEG activity were calculated from a naturalistic Memory Clinic cohort consisting of 637 individuals with different stages of cognitive impairment from subjective cognitive decline (SCD), mild cognitive impairment (MCI) and AD dementia, as well as 308 healthy elderly controls from the Swedish national aging study. Patients performed lumbar puncture and CSF was analysed for routine AD biomarkers and saved for further analysis of novel synaptic markers. In 67 MCI and AD patients FDG‐PET was performed. Result In patients, Global Field Power (GFP) in slow delta and theta frequency has inverse correlation with amyloid pathology while GFP in fast alpha and beta frequencies correlate with markers of neurodegeneration, Figure 1 a. A similar pattern of association between CSF biomarkers and Global Field Synchronisation (GSF) was found in fast alpha and beta frequencies, Figure 1b. Analysis of resting EEG microstates topography revealed association between CSF Aβ42 levels and alterations in the topography of symmetrical microstate class C, while alterations in the topography of asymmetrical microstate class B was associated with CSF p‐tau levels. There is a significant gradient‐like increase in mean contributions of asymmetrical classes A and B and decrease in contribution of symmetrical classes C and D with the more severe stage of cognitive impairment, Figure 2. In AD and MCI patients with CSF verified amyloid pathology brain glucose hypometabolism in temporoparietal lobes is significantly associated with altered EEG functional connectivity and “disconnection” of the same regions of interest on standardized EEG functional imaging technique sLORETA. Conclusion There is a selective association of qEEG power, global and regional connectivity and microstates parameters with molecular AD pathology. Ongoing study is exploring if there is a similar association with novel CSF synaptic marker neurogranin.