Hays Chelsea C, Zlatar Zvinka Z, Wierenga Christina E
VA San Diego Healthcare System, 3350 La Jolla Village Dr., MC 151B, San Diego, CA, 92161, USA.
SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, 6363 Alvarado Court, Suite 103, San Diego, CA, 92120, USA.
Cell Mol Neurobiol. 2016 Mar;36(2):167-79. doi: 10.1007/s10571-015-0261-z. Epub 2016 Feb 22.
There is accumulating evidence suggesting that changes in brain perfusion are present long before the clinical symptoms of Alzheimer's disease (AD), perhaps even before amyloid-β accumulation or brain atrophy. This evidence, consistent with the vascular hypothesis of AD, implicates cerebral blood flow (CBF) in the pathogenesis of AD and suggests its utility as a biomarker of preclinical AD. The extended preclinical phase of AD holds particular significance for disease modification, as treatment would likely be most effective in this early asymptomatic stage of disease. This highlights the importance of identifying reliable and accurate biomarkers of AD that can differentiate normal aging from preclinical AD prior to clinical symptom manifestation. Cerebral perfusion, as measured by arterial spin labeling magnetic resonance imaging (ASL-MRI), has been shown to distinguish between normal controls and adults with AD. In addition to demonstrating diagnostic utility, CBF has shown usefulness as a tool for identifying those who are at risk for AD and for predicting subtle cognitive decline and conversion to mild cognitive impairment and AD. Taken together, this evidence not only implicates CBF as a useful biomarker for tracking disease severity and progression, but also suggests that ASL-measured CBF may be useful for identifying candidates for future AD treatment trials, especially in the preclinical, asymptomatic phases of the disease.
越来越多的证据表明，在阿尔茨海默病（AD）出现临床症状之前很久，甚至可能在淀粉样β蛋白积累或脑萎缩之前，脑灌注就已经发生了变化。这一证据与AD的血管假说一致，表明脑血流量（CBF）在AD的发病机制中起作用，并提示其作为临床前AD生物标志物的效用。AD延长的临床前期对疾病修饰具有特别重要的意义，因为在疾病的这个早期无症状阶段进行治疗可能最有效。这凸显了识别可靠且准确的AD生物标志物的重要性，这些生物标志物能够在临床症状出现之前区分正常衰老和临床前AD。通过动脉自旋标记磁共振成像（ASL-MRI）测量的脑灌注已被证明能够区分正常对照和患有AD的成年人。除了具有诊断效用外，CBF还被证明是一种有用的工具，可用于识别有AD风险的人，并预测细微的认知衰退以及向轻度认知障碍和AD的转化。综上所述，这些证据不仅表明CBF是追踪疾病严重程度和进展的有用生物标志物，还表明通过ASL测量的CBF可能有助于识别未来AD治疗试验的候选者，尤其是在疾病的临床前无症状阶段。
