TMS‐based measures of cortical excitability are related to distributed atrophy in early Alzheimer’s disease

• Published in: Alzheimer's & dementia Vol. 19; no. S16
• Main Authors: Buss, Stephanie S., Zeng, Victor, Manning, Daniel, Touroutoglou, Alexandra, Dickerson, Brad C., Press, Daniel Z., Shafi, Mouhsin, Pascual‐Leone, Alvaro, Fried, Peter J.
• Format: Journal Article
• Language: English
• Published: 01.12.2023
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.079094

Background Alzheimer’s disease (AD) is associated with increased cortical excitability, including an elevated risk of seizures. Transcranial magnetic stimulation with electromyography (TMS‐EMG‐EEG) can be used to index intracortical excitability. Prior work has shown that TMS‐based excitability measures are altered in AD and are related to disease severity. However, it is not yet known how TMS‐EMG measures are related to neurodegeneration within brain regions affected by AD. Method TMS‐EMG was applied to left motor cortex (M1) in 22 participants with biomarker‐confirmed mild cognitive impairment due to AD (early AD, aged 70.5±8.4, 11 females). Single pulse TMS was preformed to measure resting motor threshold (RMT) and motor evoked potential amplitude (MEP Amplitude). Paired‐pulse TMS was preformed to measure short interval intracortical inhibition (SICI, GABA‐ergic) and intracortical facilitation (ICF, glutamatergic). In 5 participants, TMS‐evoked responses on EEG were also obtained during single‐pulse stimulation to M1 and the inferior parietal lobe (IPL), and the local mean field amplitude (LMFA) was computed from 15 to 40 msec after the TMS pulse. Structural MRI scans for each participant were processed using Freesurfer to obtain cortical thickness measurements within the distributed Alzheimer‐signature brain regions (AD‐signature atrophy). The primary analyses tested the relationship between each TMS measure and AD‐signature atrophy using separate linear models, controlling for age. For TMS‐EEG analysis, effect sizes were reported in lieu of p‐values given the small sample sizes. Result In early AD, SICI was related to AD‐signature atrophy (R2 adj = 0.40, B = ‐0.13, p = 0.018; Fig1), with less intracortical inhibition related to greater atrophy. RMT, MEP Amplitude, and ICF were not related to AD‐signature atrophy (p‐values>0.105). There was a large effect size of IPL LMFA on AD‐signature atrophy (R2 adj = 0.70), while the effect size of M1 was small (R2 adj = ‐0.19). Conclusion Decreased intracortical inhibition is related to increased AD‐signature atrophy in early AD. Decreased function of GABA‐A circuitry related to cortical atrophy may play a role in the development of cortical hyperexcitability in AD. Our preliminary results further suggests that TEPs from stimulation of IPL, a node of the default mode network and an area commonly showing AD pathology, may also be related to AD‐signature atrophy.