The Clinical Picture of Alzheimer's Disease in the Decade Before Diagnosis: Clinical and Biomarker Trajectories
The Clinical Picture of Alzheimer's Disease in the Decade Before Diagnosis: Clinical and Biomarker Trajectories
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DOI：
10.4088/jcp.15m09989
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发表时间：
2016-03-01
影响因子：
5.3
通讯作者：
Ritchie, Craig W.
中科院分区：
文献类型：
--
作者：
Ritchie, Karen;Carriere, Isabelle;Ritchie, Craig W.
目的：越来越多的证据表明，阿尔茨海默病在痴呆症诊断前至少十年就开始了。疾病的早期识别将对干预具有重要意义;然而，目前的临床前变化模型是理论性的，需要从经验观察中进行验证。此外，这些模型没有纳入精神病学feature.Method：临床和生物学指标进行了检查，在基线（1999-2001年）在9,076人年龄在65岁及以上。一项巢式病例对照研究包括830例在10年随访期间根据DSM-IV标准诊断的阿尔茨海默病患者和两倍的对照组。通过将基线和诊断之间的距离作为临床前阶段的长度，使用非参数局部加权平滑分析估计疾病标志物轨迹。结果：与对照组相比，在截短淀粉样蛋白β的截距和斜率上观察到病例的显著差异（40）（P = 0.006; P = 0.003），C反应蛋白（P = 0.03; P = 0.05），语言流畅性（P < .0001; P < .0001），视觉回忆（P <0.0001; P = 0.007）和海马体积（P = 0.0002; P = 0.04）以及仅对截短的淀粉样蛋白β（42）的斜率（P = 0.01）。的情况下，表现出较高水平的抑郁症状（P = .003），保持稳定，超过10年的diagnosis.Conclusions：假设现有的理论模型，血浆淀粉样蛋白β水平的变化，海马萎缩，认知功能丧失，和C-反应蛋白已经观察到10年前诊断。认知能力下降的加速似乎伴随着淀粉样蛋白积累的显著增加，抑郁性痴呆症持续处于较高水平。总的来说，临床和生物学标志物并不遵循相同的轨迹;临床图像根据与痴呆症的距离而变化。(C)版权所有2016 Physicians Postgraduate Press，Inc.
Objective: Increasing evidence suggests that Alzheimer's disease begins at least a decade before the diagnosis of dementia. Earlier identification of the disease will have important implications for intervention; however, current models of preclinical changes are theoretical and require verification from empirical observations. Furthermore, these models have not incorporated psychiatric features.Method: Clinical and biological markers were examined at baseline (1999-2001) in 9,076 people aged 65 years and older. A nested case-control study included 830 cases with Alzheimer's disease diagnosed by DSM-IV criteria during the 10-year follow-up and twice as many controls. By taking the distance between baseline and diagnosis as the length of the preclinical period, disease marker trajectories were estimated using nonparametric locally weighted smoothing analysis.Results: Significant differences for the cases compared to the controls were observed on both intercept and slope for truncated amyloid beta(40) (P = .006; P = .003, respectively), C-reactive protein (P = .03; P = .05), verbal fluency (P < .0001; P < .0001), visual recall (P < .0001; P = .007), and hippocampal volume (P = .0002; P = .04) and on the slope only for truncated amyloid beta(42) (P = .01). The cases showed higher levels of depressive symptoms (P = .003), which remained stable over the 10 years to diagnosis.Conclusions: As hypothesized by existing theoretical models, changes in plasma amyloid beta levels, hippocampal atrophy, cognitive loss, and C-reactive protein are already observed up to 10 years before diagnosis. An acceleration in cognitive decline appears to follow a significant increase in amyloid accumulation, and depressive symptomatology remains at a constantly higher level. Overall, clinical and biological markers do not follow the same trajectories; the clinical picture changes according to distance from dementia. (C) Copyright 2016 Physicians Postgraduate Press, Inc.