Di Fazio Chiara, Tamietto Marco, Stanziano Mario, Nigri Anna, Scaliti Eugenio, Palermo Sara
Department of Psychology, University of Turin, 10124 Turin, Italy.
International School of Advanced Studies, University of Camerino, 62032 Camerino, Italy.
Brain Sci. 2025 Feb 24;15(3):237. doi: 10.3390/brainsci15030237.
: Cognitive decline and Alzheimer's disease (AD) pose a major challenge for the ageing population, with impaired synaptic plasticity playing a central role in their pathophysiology. This article explores the hypothesis that cortico-cortical paired associative stimulation (ccPAS), a non-invasive brain stimulation technique, can restore synaptic function by targeting impaired spike-timing-dependent plasticity (STDP), a key mechanism disrupted in AD. : We reviewed existing studies investigating the effects of ccPAS on neuroplasticity in both ageing and AD populations. : Findings suggest age-specific effects, with ccPAS improving motor performance in young adults but showing limited efficacy in older adults, likely due to age-related declines in synaptic plasticity and cortical excitability. In AD, ccPAS studies reveal significant impairments in long-term potentiation (LTP)-like plasticity, while long-term depression (LTD)-like mechanisms appear relatively preserved, emphasising the need for targeted neuromodulation approaches. : Despite promising preliminary results, evidence remains limited and largely focused on motor function, with the impact of ccPAS on cognitive domains still underexplored. To bridge this gap, future research should focus on larger and more diverse cohorts to optimise ccPAS protocols for ageing and AD populations and investigate its potential for enhancing cognitive function. By refining stimulation parameters and integrating neuroimageing-based personalisation strategies, ccPAS may represent a novel therapeutic approach for mitigating neuroplasticity deficits in ageing and neurodegenerative conditions.
认知能力下降和阿尔茨海默病（AD）对老年人群构成了重大挑战，其中突触可塑性受损在其病理生理学中起着核心作用。本文探讨了一种假说，即皮质-皮质配对联想刺激（ccPAS），一种非侵入性脑刺激技术，可以通过针对受损的依赖于尖峰时间的可塑性（STDP）来恢复突触功能，STDP是AD中被破坏的关键机制。我们回顾了现有研究，这些研究调查了ccPAS对老年人群和AD人群神经可塑性的影响。研究结果表明存在年龄特异性效应，ccPAS可改善年轻人的运动表现，但在老年人中效果有限，这可能是由于与年龄相关的突触可塑性和皮质兴奋性下降所致。在AD中，ccPAS研究揭示了类似长时程增强（LTP）的可塑性存在显著损伤，而类似长时程抑制（LTD）的机制似乎相对保留，这强调了需要有针对性的神经调节方法。尽管初步结果很有前景，但证据仍然有限，且主要集中在运动功能方面，ccPAS对认知领域的影响仍未得到充分探索。为了弥补这一差距，未来的研究应聚焦于更大、更多样化的队列，以优化针对老年人群和AD人群的ccPAS方案，并研究其增强认知功能的潜力。通过优化刺激参数并整合基于神经影像学的个性化策略，ccPAS可能代表一种减轻衰老和神经退行性疾病中神经可塑性缺陷的新型治疗方法。
