Lanza Giuseppe, Fisicaro Francesco, Dubbioso Raffaele, Ranieri Federico, Chistyakov Andrei V, Cantone Mariagiovanna, Pennisi Manuela, Grasso Alfio Antonio, Bella Rita, Di Lazzaro Vincenzo
Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy.
Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, Troina, Italy.
Front Aging Neurosci. 2022 Sep 26;14:995000. doi: 10.3389/fnagi.2022.995000. eCollection 2022.
Although primary degenerative diseases are the main cause of dementia, a non-negligible proportion of patients is affected by a secondary and potentially treatable cognitive disorder. Therefore, diagnostic tools able to early identify and monitor them and to predict the response to treatment are needed. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological technique capable of evaluating and in "real time" the motor areas, the cortico-spinal tract, and the neurotransmission pathways in several neurological and neuropsychiatric disorders, including cognitive impairment and dementia. While consistent evidence has been accumulated for Alzheimer's disease, other degenerative cognitive disorders, and vascular dementia, to date a comprehensive review of TMS studies available in other secondary dementias is lacking. These conditions include, among others, normal-pressure hydrocephalus, multiple sclerosis, celiac disease and other immunologically mediated diseases, as well as a number of inflammatory, infective, metabolic, toxic, nutritional, endocrine, sleep-related, and rare genetic disorders. Overall, we observed that, while in degenerative dementia neurophysiological alterations might mirror specific, and possibly primary, neuropathological changes (and hence be used as early biomarkers), this pathogenic link appears to be weaker for most secondary forms of dementia, in which neurotransmitter dysfunction is more likely related to a systemic or diffuse neural damage. In these cases, therefore, an effort toward the understanding of pathological mechanisms of cognitive impairment should be made, also by investigating the relationship between functional alterations of brain circuits and the specific mechanisms of neuronal damage triggered by the causative disease. Neurophysiologically, although no distinctive TMS pattern can be identified that might be used to predict the occurrence or progression of cognitive decline in a specific condition, some TMS-associated measures of cortical function and plasticity (such as the short-latency afferent inhibition, the short-interval intracortical inhibition, and the cortical silent period) might add useful information in most of secondary dementia, especially in combination with suggestive clinical features and other diagnostic tests. The possibility to detect dysfunctional cortical circuits, to monitor the disease course, to probe the response to treatment, and to design novel neuromodulatory interventions in secondary dementia still represents a gap in the literature that needs to be explored.
尽管原发性退行性疾病是痴呆症的主要病因，但仍有不可忽视比例的患者受继发性且可能可治疗的认知障碍影响。因此，需要能够早期识别和监测这些疾病并预测治疗反应的诊断工具。经颅磁刺激（TMS）是一种非侵入性神经生理学技术，能够在“实时”评估多种神经和神经精神疾病（包括认知障碍和痴呆症）中的运动区域、皮质脊髓束和神经传递通路。虽然针对阿尔茨海默病、其他退行性认知障碍和血管性痴呆已经积累了一致的证据，但迄今为止，缺乏对其他继发性痴呆中可用的TMS研究的全面综述。这些病症包括正常压力脑积水、多发性硬化症、乳糜泻和其他免疫介导疾病，以及一些炎症性、感染性、代谢性、中毒性、营养性、内分泌性、睡眠相关和罕见的遗传性疾病。总体而言，我们观察到，在退行性痴呆中，神经生理学改变可能反映特定的、可能是原发性的神经病理学变化（因此可作为早期生物标志物），但对于大多数继发性痴呆形式，这种致病联系似乎较弱，其中神经递质功能障碍更可能与全身性或弥漫性神经损伤有关。因此，在这些情况下，还应努力通过研究脑回路功能改变与致病疾病引发的神经元损伤的具体机制之间的关系来理解认知障碍的病理机制。从神经生理学角度来看，虽然无法识别出可用于预测特定情况下认知衰退的发生或进展的独特TMS模式，但一些与TMS相关的皮质功能和可塑性测量指标（如短潜伏期传入抑制、短间隔皮质内抑制和皮质静息期）可能在大多数继发性痴呆中提供有用信息，特别是与提示性临床特征和其他诊断测试相结合时。在继发性痴呆中检测功能失调的皮质回路、监测病程、探究治疗反应以及设计新型神经调节干预措施的可能性仍然是文献中的一个空白，有待探索。
