Univ. Bordeaux, CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France; Centre Mémoire de Ressources et de Recherches, Pôle de Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France.
Univ. Bordeaux, CNRS, Laboratoire Bordelais de Recherche en Informatique, Talence, France.
Neurobiol Aging. 2020 Jun;90:75-83. doi: 10.1016/j.neurobiolaging.2020.01.011. Epub 2020 Feb 1.
Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer's disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of nondemented older adults with a 14-year clinical follow-up. MRI at baseline and 4 years later were assessed to measure the annualized rates of hippocampal subfields atrophy in each participant using an automatic segmentation pipeline with subsequent quality control. On the one hand, CA4 dentate gyrus was significantly more affected than the other subfields in the whole population (CA1-3: -0.68%/year; subiculum: -0.99%/year; and CA4-DG: -1.39%/year; p < 0.0001). On the other hand, the annualized rate of CA1-3 atrophy was associated with an increased risk of developing Alzheimer's clinical syndrome over time, independently of age, gender, educational level, and ApoE4 genotype (HR = 2.0; CI 95% 1.4-3.0). These results illustrate the natural history of hippocampal subfields atrophy during aging and AD by showing that the dentate gyrus is the most vulnerable subfield to the effects of aging while the cornu-ammonis is the primary target of AD pathophysiological processes, years before symptom onset.
已有多项研究调查了海马亚区在衰老和阿尔茨海默病（AD）过程中的差异易损性。结果往往相互矛盾，主要是因为这些研究工作是基于不同年龄或 AD 阶段队列的横断面测量的串联，缺乏纵向设计。在这里，我们研究了来自一个基于人群的无痴呆老年队列的 327 名参与者，这些参与者有 14 年的临床随访。对基线和 4 年后的 MRI 进行评估，使用自动分割管道对每个参与者的海马亚区萎缩的年增长率进行测量，并进行后续的质量控制。一方面，在整个人群中，CA4 齿状回比其他亚区受影响更大（CA1-3：-0.68%/年；下托：-0.99%/年；CA4-DG：-1.39%/年；p<0.0001）。另一方面，CA1-3 的年增长率与随着时间的推移发生阿尔茨海默病临床综合征的风险增加有关，这与年龄、性别、教育水平和 ApoE4 基因型无关（HR=2.0；95%CI 1.4-3.0）。这些结果通过显示齿状回是最易受衰老影响的亚区，而角回是 AD 病理生理过程的主要靶区，来阐明在衰老和 AD 过程中海马亚区萎缩的自然史，在症状出现前数年就已经如此。
