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Sex-Specific regional brain activity and cognitive function in mild cognitive impairment: An rs-fMRI study
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  • Published: 06 April 2026

Sex-Specific regional brain activity and cognitive function in mild cognitive impairment: An rs-fMRI study

  • Qin Liu1 na1,
  • Ben Chen1 na1,
  • Ting Su1 na1,
  • Qiang Wang1,
  • Danyan Xu1,
  • Mingfeng Yang1,
  • Gaohong Lin1,
  • Yijie Zeng1,
  • Jingyi Lao1,
  • Shuang Liang1,
  • Jiafu Li1,
  • Kexin Yao1,
  • Zhidai Xiao1,
  • Pengbo Gao1,
  • Xiaomin Zheng1,
  • Xiaomei Zhong1 na2 &
  • …
  • Yuping Ning  ORCID: orcid.org/0000-0002-5727-27821,2,3,4 na2 

Translational Psychiatry , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Neuroscience

Abstract

Mild cognitive impairment (MCI) is widely recognized as an early stage of dementia. Epidemiological studies suggest that MCI is more prevalent in females than in males. Notably, there are sex differences in MCI-related brain changes. Resting-state functional magnetic resonance imaging (rs-fMRI) offers a valuable method for assessing brain activity during rest. This study aims to explore sex-specific regional brain activity in participants with MCI during resting states. 86 MCI participants (21 males and 65 females) and 107 normal controls (NCs) (38 males and 69 females) were included in the present study. Regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF), and fractional ALFF (fALFF) were used to assess brain activity. MCI females showed increased ReHo values in the right cerebellum inferior compared to NC females and MCI males. However, MCI males exhibited increased ReHo values in the left hippocampus compared to NC males and MCI females. ReHo values in the right cerebellum inferior were associated with visuospatial skills in MCI males, and language function in MCI females. Additionally, ReHo values in the left hippocampus were associated with attention function in MCI females but not in MCI males. In MCI participants, sex moderated the relationship between ReHo values in the right cerebellum inferior and cognitive function (visuospatial skills and language function), as well as the association between ReHo values in the left hippocampus and attention function. In conclusions, this study revealed sex differences in ReHo of right inferior cerebellum and left hippocampus in MCI, and the association between ReHo and cognitive impairment in MCI differs by sex. These sex-specific patterns of regional brain activity can aid in the development of sex-specific precision medicine.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank all the researchers and participants involved in this study.

Funding

This work was supported by Guangzhou Municipal Key Discipline in Medicine (2025-2027), Guangdong Province Key Areas Research and Development Programs-Brain Science and Brain-Inspired Intelligence Technology (2023B0303010003), National Natural Science Foundation of China (No. 82371428,No. 82171533), Natural Science Foundation of Guangdong Province, China (2024A1515011035; 2025A1515011872), The Science and Technology Program of Guangzhou Liwan District (No.202201003), Brain Science and Brain-Like Intelligence Technology (2021ZD0201800), and Guangzhou Key ClinicaSpecialty (Clinical Medical Research Institute). The funding source had no role in the study design, analysis, or interpretation of data or in the preparation of the report or decision to publish. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the funders.

Author information

Author notes

  1. These authors contributed equally: Qin Liu, Ben Chen, Ting Su.

  2. These authors jointly supervised this work: Yuping Ning, Xiaomei Zhong.

Authors and Affiliations

  1. Geriatric Neuroscience Center, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China

    Qin Liu, Ben Chen, Ting Su, Qiang Wang, Danyan Xu, Mingfeng Yang, Gaohong Lin, Yijie Zeng, Jingyi Lao, Shuang Liang, Jiafu Li, Kexin Yao, Zhidai Xiao, Pengbo Gao, Xiaomin Zheng, Xiaomei Zhong & Yuping Ning

  2. Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China

    Yuping Ning

  3. The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China

    Yuping Ning

  4. Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China

    Yuping Ning

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Contributions

QL conducted the study, collected and analyzed the data, and drafted the initial manuscript. BC conceptualized the study, interpreted the data, and contributed to manuscript revision. TS provided technical support. QW, DX, MY, GL, YZ, JL, SL, JL, KY, ZX, PG, and XZ assisted with data collection. XZ and YN critically reviewed and revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiaomei Zhong or Yuping Ning.

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The study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University. All participants provided written informed consent prior to participation. All methods were performed in accordance with the relevant guidelines and regulations.

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The authors declare no competing interests.

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Liu, Q., Chen, B., Su, T. et al. Sex-Specific regional brain activity and cognitive function in mild cognitive impairment: An rs-fMRI study. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-03985-9

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  • Received: 26 August 2025

  • Revised: 15 February 2026

  • Accepted: 10 March 2026

  • Published: 06 April 2026

  • DOI: https://doi.org/10.1038/s41398-026-03985-9

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