INTRODUCTION Responsiveness to treatment with cholinesterase inhibitors (ChEIs) is difficult to predict in Alzheimer's disease (AD). In the current review, vascular burden is considered as a potential moderator of treatment responsiveness. Cerebrovascular burden co-occurs in at least 30% of AD brains, although it is debated if vascular pathology plays a causal or synergistic role in AD pathogenesis. Vascular burden, therefore, could potentially limit response to treatment due to limited brain reserve or augment treatment efficacy as those with vascular pathology may represent a subgroup with comparable clinical expression but less progressed AD neurodegeneration. METHODS A systematic search of Web of Science, Pubmed, Scopus and EthoS identified 32 papers which met the criteria for inclusion. Association of treatment response and vascular burden across five broad markers are discussed: cerebral hypoperfusion, intima-media thickness, white matter changes, cerebral microbleeds and co-existing diagnosis of cerebrovascular disease. RESULTS Analysis of frontal regional cerebral blood flow and intima-media thickness may have pre- dictive ability to distinguish those with AD who may respond optimally to short-term treatment with ChEIs. The impact of white matter changes is less consistent; the majority of studies demons- trate no association with treatment response and those that do implicate changes in executive func- tioning. There is preliminary evidence that deep cerebral microbleeds limit treatment response in subcortical cognitive domains, but this requires replication. The use of diagnosis of co-occurring cerebrovascular disease yields no robust variability in response to ChEIs in AD. CONCLUSION There is limited evidence that markers of cerebral hypoperfusion, intima-media thick- ness and cerebral microbleeds moderate response to ChEIs. Findings for other markers of vascular burden are less consistent and do not support any moderating effect.

中文翻译：

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脑血管病理学和阿尔茨海默氏病治疗反应：系统评价。

简介在阿尔茨海默氏病（AD）中很难预测对胆碱酯酶抑制剂（ChEIs）的治疗反应。在当前的审查中，血管负担被认为是治疗反应性的潜在调节剂。至少在30％的AD大脑中同时发生脑血管负担，尽管有关血管病理在AD发病机理中是否起因或协同作用的争论仍存在争议。因此，由于有限的大脑储备或增强的治疗功效，血管负担可能会限制对治疗的反应，因为具有血管病理学的患者可能代表具有可比临床表达但进展较慢的AD神经变性的亚组。方法对Web of Science，Pubmed，Scopus和EthoS进行系统搜索，确定了32篇符合纳入标准的论文。讨论了治疗反应和血管负担在五个主要指标之间的关联：脑灌注不足，内膜中层厚度，白质变化，脑微出血和脑血管疾病的共存诊断。结果分析额叶局部脑血流量和内膜中层厚度可能具有预测能力，以区分可能对ChEIs短期治疗产生最佳反应的AD患者。白质变化的影响不太一致；大多数研究表明与治疗反应无​​关，而那些确实暗示了执行功能的改变。初步证据表明，深层脑微出血限制了皮层下认知域的治疗反应，但这需要复制。诊断共发性脑血管疾病的使用不会对AD中的ChEIs产生明显的变化。结论仅有有限的证据表明，脑灌注不足，内膜中层厚度和脑微出血标记物对ChEIs的反应中等。其他有关血管负担标记物的发现不太一致，并且不支持任何调节作用。