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.

中文翻译：

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衰老和未来阿尔茨海默氏症临床综合征中海马亚区萎缩的年化率差异

几项研究调查了海马亚区在衰老和阿尔茨海默病 (AD) 期间的不同脆弱性。结果往往相互矛盾，主要是因为这些工作是基于对不同年龄或 AD 阶段的队列的横截面测量的串联，而没有纵向设计。在这里，我们调查了 327 名来自非痴呆老年人群的 327 名参与者，并进行了 14 年的临床随访。评估基线和 4 年后的 MRI 以测量每个参与者的海马亚区萎缩的年化率，使用自动分割管道和随后的质量控制。一方面，CA4齿状回在整个人群中比其他亚区受到的影响明显更大（CA1-3：-0.68%/年；下突：-0.99%/年；CA4-DG：-1。39%/年；p < 0.0001)。另一方面，CA1-3 萎缩的年化率与随着时间的推移发展为阿尔茨海默氏症临床综合征的风险增加相关，与年龄、性别、教育水平和 ApoE4 基因型无关（HR = 2.0；CI 95% 1.4-3.0 ）。这些结果通过表明齿状回是最容易受到衰老影响的子区域，而角状回是 AD 病理生理过程的主要目标，在症状出现前数年，这些结果说明了海马亚区在衰老和 AD 期间萎缩的自然历史。