Premium
Quantitative assessment of cortical excitability in Alzheimer’s dementia and its association with clinical symptoms: A systematic review and meta‐analyses
Author(s) -
Joseph Shaylyn,
Patterson Rachel A.,
Wang Wei,
Blumberger Daniel M.,
Rajji Tarek K.,
Kumar Sanjeev
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.055549
Subject(s) - transcranial magnetic stimulation , meta analysis , dementia , neuroscience , motor cortex , electroencephalography , psychology , audiology , alzheimer's disease , disease , medicine , stimulation
Background Alzheimer’s Disease (AD) is characterized by cognitive and neuropsychiatric symptoms (NPS). Studies using electroencephalography (EEG) have shown increased epileptiform and epileptic activity in AD. Transcranial magnetic stimulation (TMS) studies have also shown abnormal cortical excitability in AD, however findings have been inconsistent. Further, relationship between cortical excitability and clinical symptoms of AD is not clear. This review and meta‐analyses aims to synthesize the existing evidence for abnormal cortical excitability in AD and its relationship with clinical symptoms. Method We systematically searched and reviewed publications that quantitatively assessed cortical excitability, using TMS resting motor threshold (rMT), active motor threshold (aMT), motor evoked potential (MEP) or directly from the cortex using TMS‐EEG via TMS‐evoked potential (TEP). Effect sizes and 95% confidence intervals (CI) of rMT and aMT were calculated using Hedges’ g and meta‐analyzed using a random effects model. Heterogeneity among studies was assessed by Cochran’s Q and I 2 statistic. Result We identified 895 publications out of which 68 were reviewed in full‐text and 37 were included in the final review. Thirty studies using rMT and seven using aMT were included in the meta‐analyses. The AD group had reduced rMT (Hedges’ g = ‐0.99, 95% CI [‐1.29, ‐0.68], p < 0.00001) and aMT (Hedges’ g = ‐0.87, 95% CI [‐1.50, ‐0.24], p < 0.00001) as compared with control groups, indicative of higher cortical excitability. Evidence of considerable heterogeneity was found across the studies (Q (29) = 85.68, p < 0.00001, I 2 =81%). Qualitative review of the literature showed some evidence of increased MEP amplitude (n = 2 studies), however findings related to TEP were inconsistent. Further, there was some evidence (n = 4 studies) supporting an inverse association between cortical excitability and global cognition. No publications reported on the relationship between cortical excitability and neuropsychiatric symptoms (NPS). Conclusion There is strong evidence of increased motor cortex excitability in AD and some evidence of an inverse association between excitability and cognition. Future studies should assess cortical excitability from non‐motor areas and examine its relationship with cognition and NPS.