Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies
Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies
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DOI：
10.1093/brain/aws173
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发表时间：
2012-08-01
期刊：
影响因子：
14.5
通讯作者：
Kantarci, Kejal
中科院分区：
文献类型：
--
作者：
Graff-Radford, Jonathan;Boeve, Bradley F.;Kantarci, Kejal
乙酰胆碱酯酶抑制剂通常用于治疗路易体痴呆患者。磁共振成像显示的海马萎缩和正电子发射断层扫描显示的β淀粉样蛋白负荷与路易体痴呆患者的阿尔茨海默病相关病理学相关到目前为止，很少有研究调查的成像标记物，预测治疗反应的患者与路易体痴呆。我们的目的是确定阿尔茨海默病相关病理学的影像学标记物，如海马体积、C-11匹兹堡化合物B正电子发射断层扫描的脑淀粉样蛋白-β负荷是否可预测路易体痴呆患者对乙酰胆碱酯酶抑制剂的治疗反应。我们对来自马约诊所阿尔茨海默病研究中心的连续治疗初治路易体痴呆患者（n = 54）进行了回顾性分析，这些患者随后接受了乙酰胆碱酯酶抑制剂治疗，并接受了磁共振成像和海马体积测定。采用Mattis痴呆评定量表进行基线和随访评估。根据痴呆评定量表可靠性变化指标将受试者分为可靠性改善、稳定或可靠性下降三组。海马体积与治疗反应之间的关联通过协方差分析进行检验，该协方差分析调整了基线痴呆评定量表、年龄、性别、磁共振场强和痴呆评定量表间隔。7名受试者在磁共振成像的12周内接受了C-11匹兹堡化合物B成像。计算这些患者的整体皮质C-11匹兹堡化合物B保留（按小脑保留比例缩放）。使用保守的心理测量方法评估治疗反应，有12例患者的可靠下降，29例稳定的情况下，13例可靠的改善。改善组的平均波幅显著大于下降组（P = 0.02）和稳定组（P = 0.04）。探索性分析显示，改善组的颞叶和顶叶灰质体积大于下降组（P < 0.05）。两名C-11匹兹堡化合物B正电子发射断层扫描阳性的患者在治疗后下降，而C-11匹兹堡化合物B正电子发射断层扫描阴性的患者在治疗后改善或稳定。路易体痴呆患者不具有共存阿尔茨海默病相关病理学的成像特征，更有可能通过乙酰胆碱酯酶抑制剂治疗改善认知。
Acetylcholinesterase inhibitors are commonly used to treat patients with dementia with Lewy bodies. Hippocampal atrophy on magnetic resonance imaging and amyloid-beta load on positron emission tomography are associated with the Alzheimer's disease-related pathology in patients with dementia with Lewy bodies. To date, few studies have investigated imaging markers that predict treatment response in patients with dementia with Lewy bodies. Our objective was to determine whether imaging markers of Alzheimer's disease-related pathology such as hippocampal volume, brain amyloid-beta load on C-11 Pittsburgh compound B positron emission tomography predict treatment response to acetylcholinesterase inhibitors in patients with dementia with Lewy bodies. We performed a retrospective analysis on consecutive treatment-naive patients with dementia with Lewy bodies (n = 54) from the Mayo Clinic Alzheimer's Disease Research Centre who subsequently received acetylcholinesterase inhibitors and underwent magnetic resonance imaging with hippocampal volumetry. Baseline and follow-up assessments were obtained with the Mattis Dementia Rating Scale. Subjects were divided into three groups (reliable improvement, stable or reliable decline) using Dementia Rating Scale reliable change indices determined previously. Associations between hippocampal volumes and treatment response were tested with analysis of covariance adjusting for baseline Dementia Rating Scale, age, gender, magnetic resonance field strength and Dementia Rating Scale interval. Seven subjects underwent C-11 Pittsburgh compound B imaging within 12 weeks of magnetic resonance imaging. Global cortical C-11 Pittsburgh compound B retention (scaled to cerebellar retention) was calculated in these patients. Using a conservative psychometric method of assessing treatment response, there were 12 patients with reliable decline, 29 stable cases and 13 patients with reliable improvement. The improvers had significantly larger hippocampi than those that declined (P = 0.02) and the stable (P = 0.04) group. An exploratory analysis demonstrated larger grey matter volumes in the temporal and parietal lobes in improvers compared with those who declined (P < 0.05). The two patients who had a positive C-11 Pittsburgh compound B positron emission tomography scan declined and those who had a negative C-11 Pittsburgh compound B positron emission tomography scan improved or were stable after treatment. Patients with dementia with Lewy bodies who do not have the imaging features of coexistent Alzheimer's disease-related pathology are more likely to cognitively improve with acetylcholinesterase inhibitor treatment.