{"title":"TMS-derived short afferent inhibition discriminates cognitive status in older adults without dementia","authors":"","doi":"10.1016/j.nbas.2024.100123","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589958924000197/pdfft?md5=503c1b66230036c6b85cf844ec28c8b3&pid=1-s2.0-S2589958924000197-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging brain","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589958924000197","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
衰老是一个复杂多样的生物过程,其特点是分子、细胞和组织逐渐受损,导致生理完整性丧失,更容易发生病变。这种生物多样性与千变万化的认知轨迹相对应,而影响衰老大脑恢复能力的遗传和环境因素又进一步加剧了这种多样性。鉴于这种复杂性,我们需要一种神经生理指标,它不仅能辨别生理和病理衰老,还能与认知轨迹紧密结合。经颅磁刺激(TMS)作为一种非侵入性的脑刺激工具,可以描述大脑皮层兴奋性的特征,因此在这方面可能具有实用价值。特别是,作为中枢胆碱能功能的代表,短感觉抑制(SAI)功能障碍与阿尔茨海默病及相关痴呆症(ADRD)后期的认知障碍密切相关。在这项研究中,我们对健康的年轻人和老年人的 SAI 进行了评估,这些人虽然没有临床诊断,但根据 Jak/Bondi 精算标准被算法分类为认知正常(CN)或认知受损(CI)。我们的报告显示,与年轻人相比,老年认知障碍组群中的SAI得到了保留,而与年轻人和认知障碍老年人相比,老年认知障碍组群中的SAI明显减弱。此外,SAI 的减弱与持续注意力和工作记忆的受损有显著关联。作为中枢胆碱能缺陷的替代测量指标,我们讨论了 SAI 在鉴别生理性和病理性衰老方面的潜在价值。