Small-vessel diseases (SVDs) of the brain are involved in about one-fourth of ischemic strokes and a vast majority of intracerebral hemorrhages and are responsible for nearly half of dementia cases in the elderly. SVDs are a heavy burden for society, a burden that is expected to increase further in the absence of significant therapeutic advances, given the aging population. Here, we provide a critical appraisal of currently available therapeutic approaches for nonamyloid sporadic SVDs that are largely based on targeting modifiable risk factors. We review what is known about the pathogenic mechanisms of vascular risk factor-related SVDs and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most frequent hereditary SVD, and elaborate on two mechanism-based therapeutic approaches worth exploring in sporadic SVD and CADASIL. We conclude by discussing opportunities and challenges that need to be tackled if efforts to achieve significant therapeutic advances for these diseases are to be successful.

中文翻译：

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减少大脑非淀粉样小血管疾病的影响的前景。

大脑的小血管疾病（SVDs）参与约四分之一的缺血性中风和绝大多数的脑出血，并且占老年人痴呆症病例的近一半。SVD对社会来说是沉重的负担，鉴于人口老龄化，如果没有明显的治疗进展，预计这种负担会进一步增加。在这里，我们对非淀粉样散发性SVD的当前可用治疗方法进行了严格的评估，这些方法主要基于针对可修改的危险因素。我们回顾了有关血管危险因素相关SVD和脑常染色体显性动脉病变伴皮质下梗死和白质脑病（CADASIL）（最常见的遗传性SVD）的致病机制的了解，并详细阐述了两种基于机制的治疗方法，值得在散发性SVD和CADASIL中进行探索。最后，我们讨论了要使这些疾病取得重大治疗进展的努力就必须解决的机遇和挑战。