Abstract
Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer’s disease (AD) is a major scientific challenge.Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level.Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)].Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD.Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD.
Highlights
The term mild cognitive impairment (MCI) describes an intermediate stage in the trajectory from normal cognition to dementia (Petersen et al, 2018)
Due to the small size of prodromal to AD-MCI (pAD-MCI) and npAD-MCI subsamples, we did not look for any possible difference between them and instead we focused on the channels in which there was a significant [false discovery rate (FDR), adjusted] post hoc difference between the amnestic MCI (aMCI) and controls
Transcranial Magnetic Stimulation-Evoked Electroencephalogram Responses The grand average M1-evoked EEG activity following transcranial magnetic stimulation (TMS) in the aMCI and controls is shown in Figure 1, along with the source of each global mean field power (GMFP) peak
Summary
The term mild cognitive impairment (MCI) describes an intermediate stage in the trajectory from normal cognition to dementia (Petersen et al, 2018). Both EEG and TMS may be suitable screening methods as they are widely available, non-invasive, and low cost (Rossini et al, 2013) This body of work has shown that generalized slowing of the brain rhythms, reduced network complexity in EEG organization (Babiloni et al, 2016), increased cortical excitability (Ferreri et al, 2003, 2011b), altered intracortical connectivity, and disrupted plasticity in TMS-perturbed networks (Guerra et al, 2015; Benussi et al, 2018; Bologna et al, 2020; Di Lorenzo et al, 2020; Colella et al, 2021) are the neurophysiological hallmarks of AD progression (Rossini et al, 2020). And affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer’s disease (AD) is a major scientific challenge
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