Selective association of EEG microstates with clinical symptoms and mutation status in monogenic Alzheimer disease

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.