Decreased Global EEG Synchronization in Amyloid Positive Mild Cognitive Impairment and Alzheimer's Disease Patients-Relationship to APOE ε4.

Vesna Jelic,Una Smailovic,Thomas Koenig,Charlotte Johansson,Caroline Graff,Ingemar Kåreholt

doi:10.3390/brainsci11101359

Abstract

The apolipoprotein E (APOE) ε4 allele is a risk factor for Alzheimer’s disease (AD) that has been linked to changes in brain structure and function as well as to different biological subtypes of the disease. The present study aimed to investigate the association of APOE ε4 genotypes with brain functional impairment, as assessed by quantitative EEG (qEEG) in patients on the AD continuum. The study population included 101 amyloid positive patients diagnosed with mild cognitive impairment (MCI) (n = 50) and AD (n = 51) that underwent resting-state EEG recording and CSF Aβ42 analysis. In total, 31 patients were APOE ε4 non-carriers, 42 were carriers of one, and 28 were carriers of two APOE ε4 alleles. Quantitative EEG analysis included computation of the global field power (GFP) and global field synchronization (GFS) in conventional frequency bands. Amyloid positive patients who were carriers of APOE ε4 allele(s) had significantly higher GFP beta and significantly lower GFS in theta and beta bands compared to APOE ε4 non-carriers. Increased global EEG power in beta band in APOE ε4 carriers may represent a brain functional compensatory mechanism that offsets global EEG slowing in AD patients. Our findings suggest that decreased EEG measures of global synchronization in theta and beta bands reflect brain functional deficits related to the APOE ε4 genotype in patients that are on a biomarker-verified AD continuum.

Highlights

All patients were recruited at the Clinic for Cognitive Disorders, Karolinska University Hospital Huddinge, Stockholm, Sweden and underwent comprehensive clinical assessment, computed tomography (CT) and/or magnetic resonance brain imaging (MRI), resting-state EEG recording, cerebrospinal fluid (CSF) sampling, analysis of Alzheimer’s disease (AD) biomarkers (Aβ42, phospho tau (p-tau), and total tau (t-tau)), and apolipoprotein E (APOE) genotyping of peripheral blood-DNA
We further report that Aβ positive APOE ε4 carriers exhibit lower global field synchronization (GFS) in the theta band compared to APOE ε4 non-carriers
We reported an increase in beta power as the only significant change in global EEG power measures in amyloid positive APOE ε4 heterozygous and homozygous carriers compared to non-carriers, partly supporting recent reports from de Waal and colleagues that demonstrated less severe EEG slowing in APOE

Summary

Introduction

Alzheimer’s disease (AD) is the most common form of dementia with distinct neuropathological changes and a heterogeneous clinical presentation. The disease is neuropathologically characterized by the gradual accumulation of amyloid-β 42 (Aβ42) and hyperphosphorylated tau proteins in the brain tissue in the form of senile plaques and neurofibrillary tangles, respectively [1,2]. AD can present with different clinical symptomatology in its typical and atypical forms, depending on whether memory or other specific cognitive domains are affected [3]. These individual differences in the vulnerability of the human brain to the AD-associated neuropathology depend on several elements, including genetic predisposition, environmental effect, and lifestyle factors [4,5,6]

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