MRS shows abnormalities before symptoms in familial Alzheimer disease
MRS shows abnormalities before symptoms in familial Alzheimer disease
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DOI：
10.1212/01.wnl.0000201237.05869.df
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发表时间：
2006-03-14
期刊：
影响因子：
9.9
通讯作者：
Rossor, MN
中科院分区：
文献类型：
--
作者：
Godbolt, AK;Waldman, AD;Rossor, MN
背景：阿尔茨海默病（AD）的病理变化在症状出现前几年就开始了。MRS具有检测反映这种早期病理变化的代谢异常的潜力。早老素1（PS1）和淀粉样前体蛋白（APP）突变携带者发生AD的风险接近100%，可在症状发作前进行研究。研究方法：短回波时间质子MR波谱采集自PS1或APP突变的症状前携带者（"症状前突变携带者"[PMC]; n = 7）和年龄和性别匹配的对照受试者（n = 6）的中线后扣带回体素。测定N-乙酰天冬氨酸（NAA）、肌醇（MI）和含胆碱化合物（Cho）与肌酸（Cr）的比值，并计算NAA/MI。对数转换后进行回归分析和t检验。结果：PMC和对照组受试者的年龄和性别相匹配。PMC受试者在预期症状发作前1.7至21.6年（平均9.8年），根据家族特异性平均发病年龄预测。年龄对代谢物比率没有显著影响。对照受试者的几何平均值比值如下：NAA/Cr = 1.75，MI/Cr = 0.59，NAA/MI = 2.95。与对照组相比，PMC中NAA/Cr和NAA/MI显著降低（NAA/Cr平均降低10%[95% CI 2 - 18%]; NAA/MI平均降低25%[95% CI 3 - 44%]）。PMC中MI/Cr增加，但差异未达到显著性（增加19%[95% CI 1%降低至41%增加]; p = 0.07）。在PMC中，NAA/MI（p = 0.001）和MI/Cr（p = 0.002）的降低与预期发病年龄的接近程度相关。结论：在阿尔茨海默病预期发病前数年，症状前突变携带者的代谢变化是可检测的。其幅度与预期发病年龄的接近程度有关。
Background: Pathologic change in Alzheimer disease (AD) begins some years before symptoms. MRS has the potential to detect metabolic abnormalities reflecting this early pathologic change. Presenilin 1 (PS1) and amyloid precursor protein (APP) mutation carriers have a nearly 100% risk of developing AD and may be studied prior to symptom onset. Methods: Short echo time proton MR spectra were acquired from a midline posterior cingulate voxel in presymptomatic carriers of PS1 or APP mutations ("presymptomatic mutation carriers" [PMCs]; n = 7) and age- and sex-matched control subjects (n = 6). Ratios of N-acetyl aspartate (NAA), myo-inositol (MI), and choline-containing compounds (Cho) to creatine (Cr) were measured and NAA/MI calculated. Regression analyses and t tests were performed after log transformation. Results: PMC and control subjects were matched for age and sex. PMC subjects were 1.7 to 21.6 years (mean 9.8 years) before expected symptom onset, predicted from family-specific mean age at onset. Age did not significantly affect metabolite ratios. Geometric mean ratios in control subjects were as follows: NAA/Cr = 1.75, MI/Cr = 0.59, and NAA/MI = 2.95. NAA/Cr and NAA/MI were significantly reduced in PMC relative to controls (NAA/Cr mean decrease 10% [95% CI 2 to 18%]; NAA/MI mean decrease 25% [95% CI 3 to 44%]). MI/Cr was increased in PMC, but the differences did not achieve significance (19% increase [95% CI 1% decrease to 41% increase]; p = 0.07)). In PMCs, reduction in NAA/MI (p = 0.001) and MI/Cr (p = 0.002) were related to proximity of expected age at onset. Conclusions: Metabolic changes are detectable in presymptomatic mutation carriers years before expected onset of Alzheimer disease. Their magnitude is related to proximity of expected age at onset.