Prodromal Alzheimer's Disease: Successive Emergence of the Clinical Symptoms
Prodromal Alzheimer's Disease: Successive Emergence of the Clinical Symptoms
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DOI：
10.1002/ana.21509
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发表时间：
2008-11-01
影响因子：
11.2
通讯作者：
Dartigues, Jean Francois
中科院分区：
文献类型：
--
作者：
Amieva, Helene;Le Goff, Melanie;Dartigues, Jean Francois
目的：虽然早在阿尔茨海默病(AD)的典型症状显现之前，认知缺陷就已经被发现，但之前的研究未能确定认知功能在痴呆症之前实际上何时开始下降。利用PAQUID研究的长期随访，我们检查了在AD痴呆阶段之前的14年随访期内首次临床症状的出现情况。方法：本研究依赖于从PAQUID队列中选择的病例对照样本。在队列的3777名初始受试者中，350名受试者在14年的随访中经历了AD的发展。这些病例与350名老年对照组受试者相匹配。使用混合效应线性模型的半参数扩展来描述认知、功能和抑郁量表的分数在14年随访期间的演变。结果：在语义记忆和概念形成的测量中，认知表现的第一次下降最早出现在痴呆前12年。然后，伴随着记忆力抱怨和抑郁症状的增加，出现了更多的全球缺陷。大约两年后，由于认知功能障碍，受试者开始在日常生活活动中变得略有依赖。在过去的三年中，损害显著恶化，直到受试者达到痴呆阶段。解释：这种方法描述了痴呆之前的14年，清楚地说明了AD的特别长和进行性的前驱阶段，并显示在这一阶段相继出现认知缺陷、抑郁症状和功能障碍。
Objective: Whereas cognitive deficits are known to be detectable long before the typical symptoms of Alzheimer's disease (AD) are evident, previous studies have failed to determine when cognitive functioning actually begins to decline before dementia. Utilizing the long follow-up of the PAQUID study, we examined the emergence of the first clinical symptoms over a 14-year period of follow-up before the dementia phase of AD.Methods: This study relies on a case-control sample selected from the PAQUID cohort. Of the 3,777 initial subjects of the cohort, 350 subjects experienced development of AD during the 14 years of follow-up. The cases were matched to 350 elderly control Subjects. The evolution of scores on cognitive, functional, and depression scales was described throughout the 14-year follow-up using a semiparametric extension of the mixed-effects linear model.Results: The first decline in cognitive performances appeared as early as 12 years before dementia in measures of semantic memory and conceptual formation. Then, more global deficits appeared that were concomitant with an increase in memory complaints and depressive symptoms. About 2 years later, as a consequence of cognitive dysfunction, the subjects started to become slightly dependent in their activities of daily living. In the last 3 years, the impairment significantly worsened until the subjects reached the dementia phase.Interpretation: This approach, describing the 14 years preceding dementia, provides a clear illustration of the particularly long and progressive prodromal phase of AD, and shows the Successive emergence of cognitive deficits, depressive symptoms, and functional impairment during this phase.