Ihara Masafumi
Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Japan.
Brain Nerve. 2013 Jul;65(7):801-9.
With the demographic shift in life expectancy inexorably increasing in developed countries, dementia is set to become one of the most important health problems worldwide. In recent years, cerebral small vessel disease (SVD) has received much attention as an important cause of dementia. The reason for this is twofold: firstly, arteriosclerosis (type 1 SVD) is the leading cause of vascular cognitive impairment, and secondly, cerebral amyloid angiopathy (CAA; type 2 SVD) is an almost invariable accompaniment of Alzheimer's disease. SVD is known to induce a variety of pathological changes; for example, type 1 SVD results in lacunar infarction, deep microbleeds, and white matter damage, while type 2 SVD leads to cortical microinfarcts, lobar microbleeds, and white matter damage. SVD is considered a spectrum of abnormalities, with the majority of patients experiencing symptoms from both type 1 and type 2 SVD as the disease progresses. The discouraging results of immunotherapy clinical trials for Alzheimer's disease have shifted the scientific attention from the classical neuron-centric approach towards a novel neurovascular approach. As arteries stiffen with age or with other co-morbid factors such as life-related diseases, amyloid β (Aβ) synthesis becomes upregulated, resulting in the deposition of insoluble Aβ not only in the parenchyma as senile plaques but also in the perivascular drainage pathways as CAA. Therefore, therapeutic strategies such as vasoactive drugs that enhance the patency of this Aβ drainage pathway may facilitate Aβ removal and help prevent cognitive decline in the elderly. Based on this emerging paradigm, clinical trials are warranted to investigate whether a neurovascular therapeutic approach can effectively halt cognitive decline and act as a preemptive medicine for patients at risk of dementia.
随着发达国家人口预期寿命的转变不可避免地增加,痴呆症将成为全球最重要的健康问题之一。近年来,脑小血管疾病(SVD)作为痴呆症的一个重要病因受到了广泛关注。原因有两方面:其一,动脉硬化(1型SVD)是血管性认知障碍的主要原因;其二,脑淀粉样血管病(CAA;2型SVD)几乎是阿尔茨海默病的必然伴随病症。已知SVD会引发多种病理变化;例如,1型SVD会导致腔隙性梗死、深部微出血和白质损伤,而2型SVD会导致皮质微梗死、叶微出血和白质损伤。SVD被认为是一系列异常情况,随着疾病进展,大多数患者会出现1型和2型SVD的症状。阿尔茨海默病免疫治疗临床试验令人沮丧的结果已将科学关注点从传统的以神经元为中心的方法转向一种新的神经血管方法。随着动脉因年龄增长或其他合并症因素(如生活相关疾病)而变硬,淀粉样β(Aβ)合成上调,导致不溶性Aβ不仅在实质中沉积为老年斑,还在血管周围引流途径中沉积为CAA。因此,诸如增强这种Aβ引流途径通畅性的血管活性药物等治疗策略可能有助于Aβ清除,并有助于预防老年人认知能力下降。基于这一新兴模式,有必要进行临床试验,以研究神经血管治疗方法是否能有效阻止认知能力下降,并作为痴呆症高危患者的预防药物。