Mapping Divergent Subfield-Specific Hippocampal Degeneration in Mild Cognitive Impairment Continuum: Volumetric, Cognitive, and Genetic Predictors of Accelerated Hippocampal Biological Aging

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-07-29 DOI:10.1111/cns.70548

Sadegh Ghaderi, Sana Mohammadi, Farzad Fatehi, for the Alzheimer's Disease Neuroimaging Initiative

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Abstract

Objective

To investigate hippocampal subfield atrophy and biological aging across the mild cognitive impairment (MCI) continuum, we used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Methods

A cohort of 49 participants, categorized as cognitively normal (CN, n = 16), early MCI (EMCI, n = 16), or late MCI (LMCI, n = 17), underwent comprehensive neuroimaging, neuropsychological, and genetic assessments. High-resolution 3D T1-weighted MRI scans were processed using the volBrain platform and hippocampal subfield segmentation (HIPS) pipeline to quantify hippocampal subfield volumes and estimate biological age. Statistical analyses, including ANCOVA and stepwise regression, were employed to evaluate group differences and identify predictors of hippocampal biological age.

Results

The results revealed significant volumetric reductions in LMCI, particularly within the CA1, CA4/dentate gyrus (DG), and stratum radiatum/lacunosum/moleculare (SRLM) subfields, with pronounced lateralized effects. Clinical and demographic covariates attenuated group differences in biological age, but volumetric adjustments highlighted a significant distinction between EMCI and LMCI, with EMCI exhibiting a higher biological age. Cognitive performance, as measured by the Montreal Cognitive Assessment (MoCA), emerged as a consistent predictor of biological age, while APOE ε4 carrier status was significantly elevated in LMCI patients. Regression analyses identified divergent contributions of CA2/3 (positively associated) and CA4/DG (negatively associated) volumes to biological age, underscoring the subfield-specific pathophysiological mechanisms. Asymmetry indices, although variably expressed across groups, offered limited predictive utility, with CA2/3 and CA4/DG asymmetries modestly influencing biological age.

Conclusion

These findings support the integration of subfield-specific hippocampal volumetry and cognitive assessments in early diagnostic frameworks while highlighting the need for longitudinal studies to elucidate causal pathways linking subfield atrophy, biological aging, and cognitive decline.

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在轻度认知损伤连续体中绘制不同的亚场特异性海马变性：体积、认知和加速海马生物老化的遗传预测因子

目的利用阿尔茨海默病神经影像学倡议（ADNI）的数据，研究轻度认知障碍（MCI）连续体中的海马亚区萎缩和生物老化。方法对49名认知正常（CN, n = 16）、早期轻度认知损伤（EMCI, n = 16）或晚期轻度认知损伤（LMCI, n = 17）的参与者进行了全面的神经影像学、神经心理学和遗传评估。使用volBrain平台和海马子区分割（HIPS）管道处理高分辨率3D t1加权MRI扫描，以量化海马子区体积并估计生物年龄。采用统计学分析，包括ANCOVA和逐步回归来评估组间差异，并确定海马生物年龄的预测因子。结果显示，LMCI的体积显著减少，特别是在CA1、CA4/齿状回（DG）和辐射层/空洞/分子（SRLM）亚场，并伴有明显的侧化效应。临床和人口统计学协变量减弱了生物年龄的组间差异，但体积调整强调了EMCI和LMCI之间的显著差异，EMCI表现出更高的生物年龄。通过蒙特利尔认知评估（MoCA）测量的认知能力是生物学年龄的一致预测指标，而APOE ε4携带者状态在LMCI患者中显着升高。回归分析发现CA2/3（正相关）和CA4/DG（负相关）体积对生物年龄的贡献存在差异，强调了亚场特异性病理生理机制。不对称指数虽然在各组间表达不同，但提供有限的预测效用，CA2/3和CA4/DG不对称适度影响生物年龄。这些发现支持在早期诊断框架中整合子野特异性海马体积测量和认知评估，同时强调了纵向研究的必要性，以阐明子野萎缩、生物老化和认知能力下降之间的因果关系。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.