Brain perfusion follow-up in Alzheimer's patients during treatment with acetylcholinesterase inhibitors.
Brain perfusion follow-up in Alzheimer's patients during treatment with acetylcholinesterase inhibitors.
复制标题
乙酰胆碱酯酶抑制剂治疗期间阿尔茨海默病患者的脑灌注随访。
DOI：
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发表时间：
2002
影响因子：
9.3
通讯作者：
J. Darcourt
中科院分区：
文献类型：
--
作者：
F. Nobili;M. Koulibaly;P. Vitali;O. Migneco;G. Mariani;Klaus Ebmeier;A. Pupi;P. Robert;G. Rodriguez;J. Darcourt
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阿尔茨海默病（AD）患者的短暂认知和行为稳定是长期乙酰胆碱酯酶抑制剂（AChEI）治疗的主要目标，但对治疗的反应是可变的，事实上，只有一些患者是稳定的。这通常通过临床和神经心理学量表进行评估，而功能性神经影像学可以客观评价治疗对大脑功能影响的地形相关性。本研究的目的是评估脑灌注SPECT在AD患者在慢性AChEI治疗过程中的变化与他们的认知发展。
方法
47例轻度至中度可能AD的连续门诊患者（根据国家神经和交流障碍研究所和中风-阿尔茨海默病及相关疾病协会和精神疾病诊断和统计手册[第4版标准]的定义，并且在简易精神状态检查[MMSE]上得分>或=15）在2个中心登记，并在入组时（t（0））进行99 mTc-六甲基丙烯胺肟SPECT检查。他们都开始了AChEI治疗。9例患者失访，3例患者停药。在整个观察期间接受常规AChEI治疗（多奈哌齐，5或10 mg/d;卡巴拉汀，6或9 mg/d）的其余35例患者中，仅考虑31例接受多奈哌齐的患者，以避免不同药物可能的混杂效应。31名患者完成了研究，并在15.0 ± 3.0个月后（t（1））进行了第二次SPECT检查。根据MMSE评分的最小预期年下降率，将其分为稳定（17例患者）和不稳定（14例患者）亚组，该结果来自文献的荟萃分析。通过统计参数映射分析SPECT数据。
结果
基线时，稳定和不稳定患者的年龄、性别分布、教育、MMSE评分、记忆障碍（选择性提醒试验[SRT]）、载脂蛋白E基因型、AChEI剂量方案和SPECT结果相当。SRT评分在未稳定亚组中显著降低（P < 0.01），而在稳定亚组中无显著降低。在稳定亚组中，基线和重复SPECT数据之间无显著差异。相比之下，在不稳定的亚组中，在额叶、颞叶和顶叶浅层皮层以及右半球的枕楔前叶和左半球的额叶和内侧颞叶皮层中发现了显著的灌注减少。在重复SPECT上，不稳定组的左额叶区域的局部脑血流量显著低于稳定组。
结论
尽管长期接受AChEI治疗，但认知恶化的AD患者的几个皮质区域的局部脑血流量减少，与未治疗患者中观察到的相似，而在治疗期间具有稳定认知表现的AD患者中，局部脑血流量保持稳定。
UNLABELLED
Transient cognitive and behavioral stabilization of patients with Alzheimer's disease (AD) is the main goal of long-term acetylcholinesterase inhibitor (AChEI) therapy, but response to treatment is variable and, indeed, only some of the patients are stabilized. This is usually assessed by means of clinical and neuropsychologic scales, whereas functional neuroimaging could allow objective evaluation of the topographic correlates of the effect of therapy on brain functioning. The aim of this study was to evaluate brain perfusion changes by SPECT in AD patients during chronic AChEI therapy in relation to their cognitive evolution.
METHODS
Forty-seven consecutive outpatients with mild-to-moderate probable AD (as defined by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association and the Diagnostic and Statistical Manual of Mental Disorders [4th edition criteria] and a score of > or =15 on the Mini-Mental State Examination [MMSE]) were enrolled in 2 centers over a 1-y period and underwent SPECT with 99mTc-hexamethylpropyleneamine oxime at the time of enrollment (t(0)). All of them started AChEI therapy. Nine patients were lost at follow-up, and drugs were withdrawn from 3 patients. Of the remaining 35 patients, who received regular AChEI therapy (donepezil, 5 or 10 mg/d; rivastigmine, 6 or 9 mg/d) throughout the observation period, only the 31 patients receiving donepezil were considered to avoid the possible confounding effect of different drugs. The 31 patients completed the study and a second SPECT examination was performed 15.0 +/- 3.0 mo later (t(1)). They were divided into stabilized (17 patients) and nonstabilized (14 patients) subgroups on the basis of the minimum expected annual rate of decline of the MMSE score, derived from a meta-analysis of the literature. SPECT data were analyzed by means of statistical parametric mapping.
RESULTS
At baseline, the stabilized and nonstabilized patients were comparable for age, sex distribution, education, MMSE scores, memory impairment (selective reminding test [SRT]), apolipoprotein E genotype, AChEI dose regimen, and SPECT findings. The SRT scores decreased significantly (P < 0.01) in the nonstabilized subgroup but not in the stabilized subgroup. No significant difference was found between the baseline and repeated SPECT data in the stabilized subgroup. In contrast, in the nonstabilized subgroup a significant perfusion reduction was found in the frontal, temporal, and parietal superficial cortex and in the occipital precuneus in the right hemisphere and in the frontal and mesial temporal cortex in the left hemisphere. On repeated SPECT, regional cerebral blood flow was significantly lower in a left frontal region in the nonstabilized group than in the stabilized group.
CONCLUSION
The regional cerebral blood flow decreases in several cortical regions in AD patients with cognitive deterioration despite long-term AChEI therapy, similar to that observed in untreated patients, whereas it remains stable in AD patients with stabilized cognitive performance during therapy.
眼眶和背外侧额叶灌注缺陷与阿尔茨海默病胆碱酯酶抑制剂治疗的行为反应相关。
DOI：
10.1176/jnp.12.2.209
发表时间：
2000
期刊：
The Journal of neuropsychiatry and clinical neurosciences
影响因子：
--
作者：
Mega,MS;Dinov,ID;Lee,L;O'Connor,SM;Masterman,DM;Wilen,B;Mishkin,F;Toga,AW;Cummings,JL
通讯作者：
Cummings,JL