Decreased Electroencephalography Global Field Synchronization in Slow-Frequency Bands Characterizes Synaptic Dysfunction in Amnestic Subtypes of Mild Cognitive Impairment

Una Smailovic; Daniel Ferreira; Birgitta Ausén; Nicholas James Ashton; Thomas Koenig; Henrik Zetterberg; Kaj Blennow; Vesna Jelic

doi:10.3389/fnagi.2022.755454

Decreased Electroencephalography Global Field Synchronization in Slow-Frequency Bands Characterizes Synaptic Dysfunction in Amnestic Subtypes of Mild Cognitive Impairment

Front Aging Neurosci. 2022 Apr 8:14:755454. doi: 10.3389/fnagi.2022.755454. eCollection 2022.

Authors

Una Smailovic^{1

2}, Daniel Ferreira^{1

3}, Birgitta Ausén^{1

4

5}, Nicholas James Ashton^{6

7

8

9

10}, Thomas Koenig¹¹, Henrik Zetterberg^{6

7

12

13

14}, Kaj Blennow^{6

7}, Vesna Jelic^{1

4}

Affiliations

¹ Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
² Department of Clinical Neurophysiology, Karolinska University Hospital, Stockholm, Sweden.
³ Department of Radiology, Mayo Clinic, Rochester, MN, United States.
⁴ Clinic for Cognitive Disorders, Karolinska University Hospital-Huddinge, Stockholm, Sweden.
⁵ Women's Health and Allied Health Professionals Theme, Medical Unit Medical Psychology, Karolinska University Hospital, Huddinge, Sweden.
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁷ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁸ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁹ King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, United Kingdom.
¹⁰ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, United Kingdom.
¹¹ Psychiatric Electrophysiology Unit, Translational Research Center, University Hospital of Psychiatry, Bern, Switzerland.
¹² Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, United Kingdom.
¹³ UK Dementia Research Institute at UCL, London, United Kingdom.
¹⁴ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, Hong Kong SAR, China.

Abstract

Background: Mild cognitive impairment (MCI) is highly prevalent in a memory clinic setting and is heterogeneous regarding its clinical presentation, underlying pathophysiology, and prognosis. The most prevalent subtypes are single-domain amnestic MCI (sd-aMCI), considered to be a prodromal phase of Alzheimer's disease (AD), and multidomain amnestic MCI (md-aMCI), which is associated with multiple etiologies. Since synaptic loss and dysfunction are the closest pathoanatomical correlates of AD-related cognitive impairment, we aimed to characterize it in patients with sd-aMCI and md-aMCI by means of resting-state electroencephalography (EEG) global field power (GFP), global field synchronization (GFS), and novel cerebrospinal fluid (CSF) synaptic biomarkers.

Methods: We included 52 patients with sd-aMCI (66.9 ± 7.3 years, 52% women) and 30 with md-aMCI (63.1 ± 7.1 years, 53% women). All patients underwent a detailed clinical assessment, resting-state EEG recordings and quantitative analysis (GFP and GFS in delta, theta, alpha, and beta bands), and analysis of CSF biomarkers of synaptic dysfunction, neurodegeneration, and AD-related pathology. Cognitive subtyping was based on a comprehensive neuropsychological examination. The Mini-Mental State Examination (MMSE) was used as an estimation of global cognitive performance. EEG and CSF biomarkers were included in a multivariate model together with MMSE and demographic variables, to investigate differences between sd-aMCI and md-aMCI.

Results: Patients with sd-aMCI had higher CSF phosphorylated tau, total tau and neurogranin levels, and lower values in GFS delta and theta. No differences were observed in GFP. The multivariate model showed that the most important synaptic measures for group separation were GFS theta, followed by GFS delta, GFP theta, CSF neurogranin, and GFP beta.

Conclusion: Patients with sd-aMCI when compared with those with md-aMCI have a neurophysiological and biochemical profile of synaptic damage, neurodegeneration, and amyloid pathology closer to that described in patients with AD. The most prominent signature in sd-aMCI was a decreased global synchronization in slow-frequency bands indicating that functional connectivity in slow frequencies is more specifically related to early effects of AD-specific molecular pathology.

Keywords: Alzheimer’s disease; EEG power; amnestic mild cognitive impairment (aMCI); electroencephalography; global field synchronization (GFS); synaptic dysfunction.