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. 2024 Jul 19:6:100123.
doi: 10.1016/j.nbas.2024.100123. eCollection 2024.

TMS-derived short afferent inhibition discriminates cognitive status in older adults without dementia

Mark H Sundman  1 , Jacob M Green  1 , Andrew J Fuglevand  2   3 , Ying-Hui Chou  1   4
Affiliations

TMS-derived short afferent inhibition discriminates cognitive status in older adults without dementia

Mark H Sundman et al. Aging Brain. .

Abstract

Aging is a complex and diverse biological process characterized by progressive molecular, cellular, and tissue damage, resulting in a loss of physiological integrity and heightened vulnerability to pathology. This biological diversity corresponds with highly variable cognitive trajectories, which are further confounded by genetic and environmental factors that influence the resilience of the aging brain. Given this complexity, there is a need for neurophysiological indicators that not only discern physiologic and pathologic aging but also closely align with cognitive trajectories. Transcranial Magnetic Stimulation (TMS) may have utility in this regard as a non-invasive brain stimulation tool that can characterize features of cortical excitability. Particularly, as a proxy for central cholinergic function, short-afferent inhibition (SAI) dysfunction is robustly associated with cognitive deficits in the latter stages of Alzheimer's Disease and Related Dementia (ADRD). In this study, we evaluated SAI in healthy young adults and older adults who, though absent clinical diagnoses, were algorithmically classified as cognitively normal (CN) or cognitively impaired (CI) according to the Jak/Bondi actuarial criteria. We report that SAI is preserved in the Old-CN cohort relative to the young adults, and SAI is significantly diminished in the Old-CI cohort relative to both young and CN older adults. Additionally, diminished SAI was significantly associated with impaired sustained attention and working memory. As a proxy measure for central cholinergic deficits, we discuss the potential value of SAI for discerning physiological and pathological aging.

Keywords: Cognitive Aging; Dementia; Transcranial Magnetic Stimulation.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Significant Group Differences are Exclusive to SAI: The dots represent each participant’s mean conditioned MEP amplitude plotted as a percentage of the mean unconditioned MEP amplitude. Box plot elements: the black horizontal line represents the median, the colored box expands the inter-quartile range (IQR: 25 %-75 %), and the boxplot whiskers extend to capture up to 1.5x IQR. Data points above the dotted red line were considered non-responders, as they had less than 10 % inhibition relative to their unconditioned MEP amplitude. A) Short Afferent Inhibition (SAI): The one-way ANOVA revealed a significant group effect for SAI magnitude (p < 0.001). Post-Hoc comparisons revealed that the Old-CI group had significantly diminished SAI effect relative to both the Old-CN group (padjusted < 0.01**) and the Young Group (padjusted < 0.005***). B) Posterior distributions of conditioned MEP amplitude for SAI. The black circle represents the median parameter estimate, and the black bar indicates the 95 % credibility interval. When 95 % credibility intervals do not overlap, there is strong evidence of a credible group difference as is the case for the Old-CI group compared to the other two groups. C) Long afferent inhibition (LAI) for each group. The one-way ANOVA revealed no significant group-effect for magnitude of LAI. D) Posterior distributions of conditioned MEP amplitude for LAI. The 95 % credibility intervals estimated from LAI overlap across the three groups. CI: Cognitive Impairment, CN: Cognitively Normal, N.S.: No significant difference. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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