Bordet Régis, Ihl Ralf, Korczyn Amos D, Lanza Giuseppe, Jansa Jelka, Hoerr Robert, Guekht Alla
University of Lille, Inserm, CHU, U1171 'Degenerative and vascular cognitive disorders', Lille, France.
Département de Pharmacologie Médicale, Faculté de Médecine, 1 place Verdun, 59045, Lille Cedex, France.
BMC Med. 2017 May 24;15(1):107. doi: 10.1186/s12916-017-0869-6.
Vascular cognitive impairment (VCI) is a complex spectrum encompassing post-stroke cognitive impairment (PSCI) and small vessel disease-related cognitive impairment. Despite the growing health, social, and economic burden of VCI, to date, no specific treatment is available, prompting the introduction of the concept of a disease modifier.
Within this clinical spectrum, VCI and PSCI remain advancing conditions as neurodegenerative diseases with progression of both vascular and degenerative lesions accounting for cognitive decline. Disease-modifying strategies should integrate both pharmacological and non-pharmacological multimodal approaches, with pleiotropic effects targeting (1) endothelial and brain-blood barrier dysfunction; (2) neuronal death and axonal loss; (3) cerebral plasticity and compensatory mechanisms; and (4) degenerative-related protein misfolding. Moreover, pharmacological and non-pharmacological treatment in PSCI or VCI requires valid study designs clearly stating the definition of basic methodological issues, such as the instruments that should be used to measure eventual changes, the biomarker-based stratification of participants to be investigated, and statistical tests, as well as the inclusion and exclusion criteria that should be applied.
A consensus emerged to propose the development of a disease-modifying strategy in VCI and PSCI based on pleiotropic pharmacological and non-pharmacological approaches.
血管性认知障碍（VCI）是一个复杂的谱系，包括卒中后认知障碍（PSCI）和小血管病相关认知障碍。尽管VCI对健康、社会和经济造成的负担日益加重，但迄今为止尚无特效治疗方法，这促使了疾病修饰剂概念的提出。
在这一临床谱系中，VCI和PSCI仍是进展性疾病，属于神经退行性疾病，血管病变和退行性病变的进展均导致认知功能下降。疾病修饰策略应整合药理学和非药理学的多模式方法，其多效性作用靶点包括：（1）内皮细胞和血脑屏障功能障碍；（2）神经元死亡和轴突丢失；（3）脑可塑性和代偿机制；（4）与退行性变相关的蛋白质错误折叠。此外，PSCI或VCI的药理学和非药理学治疗需要有效的研究设计，明确阐述基本方法学问题的定义，如用于测量最终变化的工具、基于生物标志物的待研究参与者分层、统计检验，以及应采用的纳入和排除标准。
已达成共识，提议基于多效性药理学和非药理学方法制定VCI和PSCI的疾病修饰策略。
