Selective association of EEG microstates with clinical symptoms and mutation status in monogenic Alzheimer disease
Charlotte Johansson1, Thomas Koenig2, Una Smailovic3
1Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Sweden; Theme Inflammation and Aging, Clinic for Cognitive Disorders, Karolinska University Hospital, Stockholm, Sweden.
Abstract:
EEG microstates are transient and short-lasting periods of stable scalp potential fields that are associated with disturbed temporal dynamics of large-scale brain networks, affected by early synaptic loss in Alzheimer disease (AD). We investigated changes in EEG microstates in presymptomatic (PMC) and symptomatic mutation carriers (SMC) compared to healthy non-carrier (NC) controls in families with autosomal dominant AD (ADAD). A total of 99 EEG recordings from 7 SMC, 17 PMC and 24 NC were selected from a Swedish ADAD cohort. Seven classes (A to G) of microstate topographical maps were fitted to their resting-state EEG. Next, microstate parameters of coverage (fraction of total recording time), duration (average time in milliseconds) and occurrence (frequency per second) of different topographical maps were assessed in repeated-measures analyses to compare differences between NC, PMC and SMC. Selective decreases in coverage of class B (SMC vs NC, p = 0.023) and class C (SMC vs PMC and NC, p = 0.017 and p = 0.004) were observed in symptomatic individuals. In contrast, mutation carriers had a decrease in coverage of class D (SMC and PMC vs NC, p = 0.015 and p = 0.001) and an increase in coverage of class E compared to controls (SMC and PMC vs NC, both p = 0.001). Thus, global brain network dynamics as described by EEG microstate classes were selectively affected in this cohort of monogenic AD, associated with either clinical symptoms (class B and C) or mutation status (class D and E). The latter suggests early mutation-related changes that are detectable already in the presymptomatic stages of disease.
Insights
EEG microstates reveal altered brain network dynamics in autosomal dominant Alzheimer disease (ADAD). Symptomatic individuals show changes linked to clinical symptoms, while presymptomatic carriers exhibit early alterations related to mutation status.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Genetics
Background:
- Alzheimer disease (AD) involves disturbed large-scale brain network dynamics, potentially indicated by electroencephalogram (EEG) microstates.
- Early synaptic loss in AD impacts temporal dynamics of brain networks.
- Autosomal dominant AD (ADAD) provides a model to study early disease-related brain changes.
Purpose of the Study:
- To investigate EEG microstate alterations in presymptomatic (PMC) and symptomatic mutation carriers (SMC) of ADAD compared to healthy non-carriers (NC).
- To identify specific EEG microstate changes associated with clinical symptoms and mutation status in ADAD.
Main Methods:
- Analysis of resting-state EEG recordings from 99 individuals (7 SMC, 17 PMC, 24 NC) from a Swedish ADAD cohort.
- Fitting seven classes (A-G) of microstate topographical maps to EEG data.
- Assessing microstate parameters (coverage, duration, occurrence) and comparing differences between NC, PMC, and SMC groups.
Main Results:
- Symptomatic individuals (SMC) showed decreased coverage of microstate classes B and C compared to non-carriers (NC).
- Mutation carriers (SMC and PMC) exhibited decreased coverage of class D and increased coverage of class E compared to NC.
- These findings suggest selective alterations in global brain network dynamics linked to clinical symptoms and mutation status.
Conclusions:
- EEG microstate dynamics are selectively affected in monogenic ADAD.
- Microstate changes correlate with clinical symptoms (classes B and C) and mutation status (classes D and E).
- Alterations in microstate classes D and E suggest early, mutation-related brain changes detectable in presymptomatic stages.
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