
Synaptic Molecular and Neurophysiological Markers Are Independent Predictors of Progression in Alzheimer’s Disease
Author(s) -
Una Smailović,
Ingemar Kåreholt,
Thomas Koenig,
Nicholas J. Ashton,
Bengt Winblad,
Kina Höglund,
Per Nilsson,
Henrik Zetterberg,
Kaj Blennow,
Vesna Jelić
Publication year - 2021
Publication title -
journal of alzheimer's disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.677
H-Index - 139
eISSN - 1875-8908
pISSN - 1387-2877
DOI - 10.3233/jad-201234
Subject(s) - neurogranin , dementia , electroencephalography , neuroscience , psychology , neurophysiology , alzheimer's disease , medicine , disease , biology , biochemistry , protein kinase c , enzyme
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.