Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease
Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease
复制标题
DOI：
10.1212/wnl.0000000000006277
复制
发表时间：
2018-10-02
期刊：
影响因子：
9.9
通讯作者：
Bateman, Randall J.
中科院分区：
文献类型：
--
作者：
McDade, Eric;Wang, Guoqiao;Bateman, Randall J.
目的评估发病，序列，和全面的生物标志物和临床措施的进展速度在整个频谱的阿尔茨海默病（AD）使用显性遗传阿尔茨海默氏症网络（DIAN）的研究和比较这些横断面estimation.MethodsWe进行了纵向临床，认知，CSF和神经影像学评估（平均2.7 [+/- 1.1]访问）在217 DIAN参与者。线性混合效应模型用于评估每个指标相对于个体估计的症状发作年数的变化，并比较突变携带者和非携带者。（在估计症状发作前25年开始），随后皮质代谢指标下降（约7-10年后），然后是认知和海马萎缩（约20年后）。CSF p-tau（181）和tau的估计值存在显著差异，横断面估计值的升高早于纵向估计值10年以上;此外，本发明还纵向估计发现CSF p-tau显著下降（181）结论这些纵向评估阐明了常染色体显性遗传病中症状前病理变化的顺序和时间动态。显性AD，信息对更好地了解疾病至关重要。这里确定的生物标志物变化模式也表明，一旦β-淀粉样变性开始，其他病理可能在不到10年后开始发展，但在症状发作前超过15年，这是旨在改变病程的干预措施的重要考虑因素。
ObjectiveTo assess the onset, sequence, and rate of progression of comprehensive biomarker and clinical measures across the spectrum of Alzheimer disease (AD) using the Dominantly Inherited Alzheimer Network (DIAN) study and compare these to cross-sectional estimates.MethodsWe conducted longitudinal clinical, cognitive, CSF, and neuroimaging assessments (mean of 2.7 [+/- 1.1] visits) in 217 DIAN participants. Linear mixed effects models were used to assess changes in each measure relative to individuals' estimated years to symptom onset and to compare mutation carriers and noncarriers.ResultsLongitudinal beta-amyloid measures changed first (starting 25 years before estimated symptom onset), followed by declines in measures of cortical metabolism (approximately 7-10 years later), then cognition and hippocampal atrophy (approximately 20 years later). There were significant differences in the estimates of CSF p-tau(181) and tau, with elevations from cross-sectional estimates preceding longitudinal estimates by over 10 years; further, longitudinal estimates identified a significant decline in CSF p-tau(181) near symptom onset as opposed to continued elevations.ConclusionThese longitudinal estimates clarify the sequence and temporal dynamics of presymptomatic pathologic changes in autosomal dominant AD, information critical to a better understanding of the disease. The pattern of biomarker changes identified here also suggests that once beta-amyloidosis begins, additional pathologies may begin to develop less than 10 years later, but more than 15 years before symptom onset, an important consideration for interventions meant to alter the disease course.