PDF(Pubmed)
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.
摘要：
衰老是一个复杂多样的生物过程,其特点是分子进化,细胞，和组织损伤，导致生理完整性的丧失和对病理的脆弱性增加。这种生物多样性与高度可变的认知轨迹相对应，这些因素进一步被影响衰老大脑弹性的遗传和环境因素所混淆。鉴于这种复杂性,神经生理学指标不仅需要识别生理和病理衰老，而且需要与认知轨迹紧密一致。经颅磁刺激(TMS)在这方面可以用作能够表征皮质兴奋性特征的非侵入性脑刺激工具。特别是,作为中枢胆碱能功能的代表，短期传入抑制(SAI)功能障碍与阿尔茨海默病和相关痴呆(ADRD)后期的认知缺陷密切相关。在这项研究中,我们评估了健康的年轻人和老年人的SAI，尽管没有临床诊断，根据Jak/Bondi精算标准，在算法上分为认知正常（CN）或认知受损（CI）。我们报告说，相对于年轻人，SAI保留在Old-CN队列中，与年轻人和CN老年人相比，Old-CI队列中的SAI显着降低。此外,SAI降低与持续注意力和工作记忆受损显著相关。作为中枢胆碱能缺陷的替代指标，我们讨论了SAI对识别生理和病理衰老的潜在价值。
