Identification of circadian-sensitive brain structure and its role in cognitive impairment and dementia

Background Circadian disruption has been suggested to induce cognitive impairment and dementia. It remains unknown which brain structures are involved in the pathology.Objective To investigate which specific brain structure alterations are associated with dementia and cognitive impairment induced by...

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Main Authors: Qing Chen, Shengfeng Wang, Jia Cao, Siwen Luo, Yimeng Wang, Mengchao He, Qiaorui Wen
Format: Article
Language:English
Published: BMJ Publishing Group 2025-05-01
Series:BMJ Mental Health
Online Access:https://mentalhealth.bmj.com/content/28/1/e301142.full
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author Qing Chen
Shengfeng Wang
Jia Cao
Siwen Luo
Yimeng Wang
Mengchao He
Qiaorui Wen
author_facet Qing Chen
Shengfeng Wang
Jia Cao
Siwen Luo
Yimeng Wang
Mengchao He
Qiaorui Wen
author_sort Qing Chen
collection DOAJ
description Background Circadian disruption has been suggested to induce cognitive impairment and dementia. It remains unknown which brain structures are involved in the pathology.Objective To investigate which specific brain structure alterations are associated with dementia and cognitive impairment induced by circadian disruption.Methods Circadian disruption was represented by two accelerometer-derived circadian variables, composite phase deviations (CPD) and relative amplitude (RA), separately reflecting circadian disruption in timing and amplitude. The outcomes include brain structures (139 imaging-derived phenotypes), cognitive test performances (seven cognitive tests) and dementia (all-cause dementia, Alzheimer’s disease, vascular dementia (AD/VD) and non-AD/VD dementia). Association analysis was used to explore the relationships between circadian disruption and brain structure alterations, cognitive test performances and dementia. Mediation analysis was conducted to investigate which brain structure alterations mediated the cognitive impairment and dementia caused by circadian disruption.Findings A total of 88 461 participants (57% female, 62.0±7.8-year old) were included. CPD and RA correlated with substantially different brain structures. All CPD-related brain structures were located in the cerebrum, whereas most RA-related brain structures were located in the cerebellum. Furthermore, only the CPD-related brain structures, including the hippocampus and thalamus, exhibited significant mediation effects accounting for up to 8.6% of the risk for dementia and 13.5% of the risk for cognitive impairment.Conclusions Circadian disruption is associated with brain structural alterations involving dementia and cognitive impairments.Clinical implications These results provide a novel insight into the mechanism underlying circadian disruption-induced neurological disorder and may propose potential preventive strategy.
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spelling doaj-art-30fd3ce61ec94427a9d51d6f9d69148a2025-08-20T01:51:16ZengBMJ Publishing GroupBMJ Mental Health2755-97342025-05-0128110.1136/bmjment-2024-301142Identification of circadian-sensitive brain structure and its role in cognitive impairment and dementiaQing Chen0Shengfeng Wang1Jia Cao2Siwen Luo3Yimeng Wang4Mengchao He5Qiaorui Wen6Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, ChinaDepartment of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing, ChinaKey Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, ChinaKey Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, ChinaKey Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, ChinaKey Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, ChinaDepartment of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing, ChinaBackground Circadian disruption has been suggested to induce cognitive impairment and dementia. It remains unknown which brain structures are involved in the pathology.Objective To investigate which specific brain structure alterations are associated with dementia and cognitive impairment induced by circadian disruption.Methods Circadian disruption was represented by two accelerometer-derived circadian variables, composite phase deviations (CPD) and relative amplitude (RA), separately reflecting circadian disruption in timing and amplitude. The outcomes include brain structures (139 imaging-derived phenotypes), cognitive test performances (seven cognitive tests) and dementia (all-cause dementia, Alzheimer’s disease, vascular dementia (AD/VD) and non-AD/VD dementia). Association analysis was used to explore the relationships between circadian disruption and brain structure alterations, cognitive test performances and dementia. Mediation analysis was conducted to investigate which brain structure alterations mediated the cognitive impairment and dementia caused by circadian disruption.Findings A total of 88 461 participants (57% female, 62.0±7.8-year old) were included. CPD and RA correlated with substantially different brain structures. All CPD-related brain structures were located in the cerebrum, whereas most RA-related brain structures were located in the cerebellum. Furthermore, only the CPD-related brain structures, including the hippocampus and thalamus, exhibited significant mediation effects accounting for up to 8.6% of the risk for dementia and 13.5% of the risk for cognitive impairment.Conclusions Circadian disruption is associated with brain structural alterations involving dementia and cognitive impairments.Clinical implications These results provide a novel insight into the mechanism underlying circadian disruption-induced neurological disorder and may propose potential preventive strategy.https://mentalhealth.bmj.com/content/28/1/e301142.full
spellingShingle Qing Chen
Shengfeng Wang
Jia Cao
Siwen Luo
Yimeng Wang
Mengchao He
Qiaorui Wen
Identification of circadian-sensitive brain structure and its role in cognitive impairment and dementia
BMJ Mental Health
title Identification of circadian-sensitive brain structure and its role in cognitive impairment and dementia
title_full Identification of circadian-sensitive brain structure and its role in cognitive impairment and dementia
title_fullStr Identification of circadian-sensitive brain structure and its role in cognitive impairment and dementia
title_full_unstemmed Identification of circadian-sensitive brain structure and its role in cognitive impairment and dementia
title_short Identification of circadian-sensitive brain structure and its role in cognitive impairment and dementia
title_sort identification of circadian sensitive brain structure and its role in cognitive impairment and dementia
url https://mentalhealth.bmj.com/content/28/1/e301142.full
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