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Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

Yifang Zhou·Xiaowei Jiang·Linzi Liu·Wenyi Xi·Linna Jia·Luyu Ren·Yixiao Xu·Shuping Tan·Lingtao Kong·Langyuan Fu·Fei Wang·Yanqing Tang
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Abstract

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50&#x202f;aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT&#xd7;diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F&#x202f;=&#x202f;4.322, P&#x202f;=&#x202f;0.041); this interaction was driven by CCT specifically in aMCI (F&#x202f;=&#x202f;4.465, P&#x202f;=&#x202f;0.038). Significant CCT&#xd7;diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F&#x202f;=&#x202f;5.429, P&#x202f;=&#x202f;0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F&#x202f;=&#x202f;6.587, P&#x202f;=&#x202f;0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F&#x202f;=&#x202f;6.550, P&#x202f;=&#x202f;0.013; F&#x202f;=&#x202f;7.097, P&#x202f;=&#x202f;0.010). No significant interaction effect on the change in hippocampal GMV was noted (P&#x202f;>&#x202f;0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

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HumansCognitive DysfunctionHippocampusFemaleAgedMagnetic Resonance ImagingCognitive TrainingMaleCase-Control StudiesAmnesiaMiddle AgedCognitive EnhancementTherapy, Computer-AssistedFollow-Up StudiesCognitive trainingFunctional connectivityGray matter volumeaMCIJournal ArticleRandomized Controlled Trial

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Yifang Zhou, Xiaowei Jiang, Linzi Liu, Wenyi Xi, Linna Jia, Luyu Ren, Yixiao Xu, Shuping Tan, Lingtao Kong, Langyuan Fu, Fei Wang, Yanqing Tang. 2026-07-30. Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.. https://doi.org/10.1016/j.jpsychires.2026.07.004

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Journal Article; Randomized Controlled Trial resourceAged subjectCase-Control Studies subjectCognitive Dysfunction subjectCognitive Enhancement subjectCognitive Training subjectFemale subjectFollow-Up Studies subjectFunctional connectivity subjectHumans subjectJournal Article subjectMagnetic Resonance Imaging subjectMale subjectMiddle Aged subjectRandomized controlled trials study

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