The notion of what qualifies as vascular dementia has varied greatly since the first mention of dementia after apoplexy in ancient literature. Current insight points towards a multifactorial cause of cognitive decline at old age, in which vascular components like atherosclerosis, arterio(lo)sclerosis, (micro)infarcts, and amyloid angiopathy play an important role alongside other markers of neurodegeneration. Cerebrovascular disease will be present in most individuals with dementia, but—just like other causes—rarely a cause on its own. The consequent limitations of nosology may be alleviated by addition of a vascular component to the recently introduced amyloid/tau/neurodegeneration etiological classification system for dementia. Meanwhile, risk of dementia is increased about 2-fold after stroke, and the prevention of (recurrent) stroke remains a cornerstone in the prevention of vascular dementia. Similarly, control of cardiovascular risk factors from middle age onwards is likely to have contributed to the reported decline in the age-specific incidence of dementia over the past decades. In conjunction with experimental studies, large-scale observational evidence from imaging, genomics, metabolomics, and alike will continue to improve our understanding of the underlying pathophysiological processes. To prevent ecological fallacies, such etiological studies in patients with dementia are best served by inclusion of subjects regardless of the presumed (single) cause of their disease.

This study aimed to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on learning and memory in a rat model of vascular dementia (VaD) and to analyze the associated mechanisms. Bilateral carotid artery occlusion (2-VO) was used to establish a rat model of VaD. High-frequency (5Hz) rTMS was performed on rats for four weeks. Spatial learning and memory abilities were evaluated using the Morris water maze (MWM), and synaptic plasticity in the hippocampus was assessed via long-term potentiation (LTP). Hippocampal expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) and three subunits of the N-methyl-D-aspartic acid receptor (NMDAR), NR1, NR2A and NR2B, was analyzed by Western blotting. Compared with the VaD group, escape latency was decreased (P<0.05) and the time spent in the target quadrant and the percentage of swimming distance within that quadrant were increased (P<0.05) in the rTMS group. LTP at hippocampal CA3-CA1 synapses was enhanced by rTMS (P<0.05). VEGF expression was up-regulated following 2-VO and was further increased by rTMS (P<0.05). BDNF, NR1 and NR2B expression was decreased in the VaD group and increased by rTMS (P<0.05). There were no significant differences in NR2A expression among the three groups. These results suggest that rTMS improved learning and memory in the VaD model rats via the up-regulation of VEGF, BDNF and NMDARs. In addition, NR2B may be more important than NR2A for LTP induction in the hippocampus during rTMS treatment of VaD.Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

背景　血管性认知障碍（VCI）不仅影响患者的生活质量，还给患者的全面功能康复带来较大困难。重复经颅磁刺激（rTMS）在神经系统和精神性疾病治疗方面的应用受到越来越多的关注，研究rTMS对VCI的疗效，对寻找非药物手段治疗VCI具有重要意义。目的　系统评价rTMS对我国VCI患者的疗效。方法　2019年10月&mdash;2020年1月，使用Cochrane协作网提供的系统评价方法，系统全面检索PubMed、Embase、EBSCO、Web of Science、Cochrane Library和中国知网数据库。同时筛查纳入文献的参考文献，结合手工检索相关期刊及灰色文献，检索时间截至2019-12-30，纳入关于rTMS治疗VCI的临床随机对照研究。由两名评价者采用Cochrane偏倚风险评估工具进行文献质量评价，采用RevMan 5.3软件进行Meta分析。结果　共纳入12篇临床随机对照文章，包括837例患者。Cochrane偏倚风险评估结果显示，12篇文献中，5篇报道了具体的随机分组方法，2篇进行了分配隐藏，2篇报道了避免测量偏倚的方法。Meta分析结果提示rTMS能够提高脑卒中患者的蒙特利尔认知评估量表（MoCA）、简易智力状态检查量表（MMSE）及Loewenstein认知功能评定表（LOTCA）评分。进行敏感性分析后，MoCA评分和MMSE评分结果采用固定效应模型，其总体效应值分别为：WMD=2.52，95%CI（2.04，3.00），P&lt;0.05；WMD=1.55，95%CI（1.04，2.07），P&lt;0.05。LOTCA评分因文献数量限制而采用定性分析，结果显示rTMS对其改善具有积极作用（P&lt;0.05）。结论　rTMS对VCI患者的认知功能具有一定改善作用。但目前仍存在临床试验不够规范和研究样本量较小等问题，未来还需要更多高质量、大样本、多中心的随机对照研究来观察rTMS对VCI的疗效。