Neural somatosensory dysfunction is masked by variable executive declines across the Alzheimer’s disease spectrum

Abstract

Background Despite decades of research suggesting that primary somatosensory cortical function is spared until relatively late in the progression of Alzheimer’s disease (AD), very few of these studies have considered the role of domain‐specific cognitive function. This is essential, as recent literature has established a robust neurocognitive relationship between attention and executive functions and somatosensory neurophysiology, and patients with AD exhibit highly variable inter‐individual declines in these cognitive domains. Method In this study, we combine the high spatio‐temporal resolution of source imaged magnetoencephalography (MEG) with an extensive battery of neuropsychological tests to examine the potential mediating role of domain‐specific cognitive declines on somatosensory neural dysfunction in AD. In a sample of 38 biomarker‐confirmed patients on the AD spectrum and a group of 18 biomarker‐negative older adults, we model mediation/suppression effects of five distinct cognitive composite domains on group differences in two neurophysiological metrics of somatosensory function using a nonparametric bootstrapping approach. Result Initial models that did not consider cognitive abilities provided weak or null support for somatosensory dysfunction in patients on the AD spectrum. However, the addition of domain‐specific cognitive scores to these models significantly increased their predictive capacity, and revealed robust differences in somatosensory function between these patients and their cognitively‐normal counterparts. The indirect effects of these cognitive variables on somatosensory group differences were significant as well, indicating a suppression effect. Specifically, across‐participant variability in processing speed declines was found to mask groupwise differences in mean somatosensory response amplitude, and similar variability in both processing speed and attention function was found to mask differences in the functional gating of redundant somatosensory information. Conclusion By considering an important potential confounder in our models of somatosensory dysfunction in patients on the AD spectrum, we show that both general somatosensory responses and the functional gating of incoming somatosensory information exhibit profound alterations in these patients. These findings hold important implications for both our understanding of functional somatosensory pathology in AD, as well as for the importance of considering the role of domain‐specific cognitive variability in future AD‐neuroimaging research.