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Changes in microstructural similarity of hippocampal subfield circuits in pathological cognitive aging

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Abstract

The hippocampal networks support multiple cognitive functions and may have biological roles and functions in pathological cognitive aging (PCA) and its associated diseases, which have not been explored. In the current study, a total of 116 older adults with 39 normal controls (NC) (mean age: 52.3 ± 13.64 years; 16 females), 39 mild cognitive impairment (MCI) (mean age: 68.15 ± 9.28 years, 14 females), and 38 dementia (mean age: 73.82 ± 8.06 years, 8 females) were included. The within-hippocampal subfields and the cortico-hippocampal circuits were assessed via a micro-structural similarity network approach using T1w/T2w ratio and regional gray matter tissue probability maps, respectively. An analysis of covariance was conducted to identify between-group differences in structural similarities among hippocampal subfields. The partial correlation analyses were performed to associate changes in micro-structural similarities with cognitive performance in the three groups, controlling the effect of age, sex, education, and cerebral small-vessel disease. Compared with the NC, an altered T1w/T2w ratio similarity between left CA3 and left subiculum was observed in the mild cognitive impairment (MCI) and dementia. The left CA3 was the most impaired region correlated with deteriorated cognitive performance. Using these regions as seeds for GM similarity comparisons between hippocampal subfields and cortical regions, group differences were observed primarily between the left subiculum and several cortical regions. By utilizing T1w/T2w ratio as a proxy measure for myelin content, our data suggest that the imbalanced synaptic weights within hippocampal CA3 provide a substrate to explain the abnormal firing characteristics of hippocampal neurons in PCA. Furthermore, our work depicts specific brain structural characteristics of normal and pathological cognitive aging and suggests a potential mechanism for cognitive aging heterogeneity.

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Data availability

All data supporting our findings are available from the corresponding author on reasonable request.

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Funding

This study was supported in part by STI2030–Major Projects (2022ZD0213400); National Natural Science Foundation of China (82201720); Shanghai Municipal Health Commission (Grant No. 202040086); and Shanghai Special Research Project on Aging and Maternal and Child Health (Grant No. 2020YJZX0121). Dr. Wu played a pivotal role in securing the funding for this research.

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Authors and Affiliations

  1. Department of Neurology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

    Min Fang & Huanghuang Huang

  2. Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), Affiliated Mental Health Center (ECNU), School of Psychology and Cognitive Science, East China Normal University, Shanghai, China

    Jie Yang & Chu-Chung Huang

  3. School of Medicine, Tongji University, Shanghai, China

    Shuying Zhang

  4. Changning Mental Health Center, Shanghai, China

    Yujie Wu & Chu-Chung Huang

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  1. Min Fang
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  6. Chu-Chung Huang
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Contributions

Conceptualization: C-CH, MF; Formal Analysis: C-CH, MF; Data Collection: MF, H-HH, S-YZ; Writing-Original Draft: C-CH, MF; Writing Review & Editing: C-CH, MF, H-HH, JY, S-YZ; All authors read and approved the final manuscript.

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Correspondence to Chu-Chung Huang.

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Fang, M., Huang, H., Yang, J. et al. Changes in microstructural similarity of hippocampal subfield circuits in pathological cognitive aging. Brain Struct Funct 229, 311–321 (2024). https://doi.org/10.1007/s00429-023-02721-z

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