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 foster 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 predictive 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 demonstrates no association with treatment response and those that do implicate changes in executive functioning. There is preliminary evidence that deep cerebral microbleeds limit treatment response in subcortical cognitive domains, but this finding 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 thickness and cerebral microbleeds moderate response to ChEIs. Findings for other markers of vascular burden are less consistent and do not support any moderating effect.

简介：在阿尔茨海默病 (AD) 中，很难预测对胆碱酯酶抑制剂 (ChEI) 治疗的反应。在当前的审查中，血管负荷被认为是治疗反应性的潜在调节因素。脑血管负担在至少 30% 的 AD 大脑中同时发生，尽管血管病理学在 AD 发病机制中是否起因果或协同作用存在争议。因此，血管负担可能会由于有限的大脑储备或促进治疗效果而限制对治疗的反应，因为那些具有血管病理学的患者可能代表具有可比临床表现但 AD 神经变性进展较轻的亚组。

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。讨论了五个广泛标志物的治疗反应和血管负荷的关联：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：额叶区域脑血流量和内膜中层厚度的分析可能具有区分 AD 患者的预测能力，这些 AD 患者可能对 ChEI 的短期治疗反应最佳。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，而那些确实涉及执行功能变化的研究。有初步证据表明，深部脑微出血限制了皮层下认知域的治疗反应，但这一发现需要重复。使用同时发生的脑血管疾病的诊断在 AD 中对 ChEI 的反应没有明显的变异性。

结论：脑灌注不足、内膜中层厚度和脑微出血的标志物可减轻对 CheIs 的反应的证据有限。其他血管负荷标志物的结果不一致，不支持任何调节作用。