Human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain
IntroductionExisting evidence indicates that HIV enters the nervous system in the early days of infection. However, the involvement of HIV in the pathogenesis of key biological aspects of the brain, such as glymphatic clearance and brain aging, and its role in explaining complex phenomena like motor...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1509093/full |
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| author | Benedictor Alexander Nguchu Benedictor Alexander Nguchu Jing Zhao Yu Lu Yifei Han Han Jin Xiaoxiao Wang Hongjun Li Peter Shaw |
| author_facet | Benedictor Alexander Nguchu Benedictor Alexander Nguchu Jing Zhao Yu Lu Yifei Han Han Jin Xiaoxiao Wang Hongjun Li Peter Shaw |
| author_sort | Benedictor Alexander Nguchu |
| collection | DOAJ |
| description | IntroductionExisting evidence indicates that HIV enters the nervous system in the early days of infection. However, the involvement of HIV in the pathogenesis of key biological aspects of the brain, such as glymphatic clearance and brain aging, and its role in explaining complex phenomena like motoric and executive dysfunction, remains unrecognized.MethodsHerein, we recruited 145 subjects to study the brain aging using brain-predicted age differences (brain-PADs) and investigate how HIV affects the typical trajectory of glymphatic clearance in aging brain. The assessment of glymphatic clearance in the aging brain was performed using a technique called "diffusion tensor image analysis along the perivascular space” (DTI-ALPS). We further evaluated the association between accelerated brain aging trajectories and cognitive performance to explain impairments observed in motor and executive functions in people living with HIV. ResultsOur results showed that subjects with HIV had increased brain-PAD in several brain structures compared to those who were HIV-negative, suggesting underlying neuropathology associated with HIV. The brain structures demonstrating accelerated aging (increased brain-PAD) include the middle frontal gyrus, pre-and post-central gyri, supramarginal gyrus, precuneus, cuneus, parietal lobule and operculum, and superior and middle occipital gyri of the left hemisphere. While normal subjects maintained typical trajectories of glymphatic clearance (as measured by the DTI-ALPS index) with age or brain-PADs for several structures, including the left central operculum, left frontal operculum, left opercular inferior frontal gyrus, and left triangular inferior frontal gyrus, none of these trajectories were maintained in subjects with HIV. Our data also show that increased brain-PAD in brain regions was associated with lower performance in motor and executive functions. DiscussionThese findings suggest that HIV infection accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain, which may explain the complex mechanisms underlying cognitive impairment in motor and executive domains often seen in HIV patients. These new insights may shift our understanding of HIV pathology and aid the development of new therapeutic targets, contrary to previous approaches. |
| format | Article |
| id | doaj-art-5e398e01f99f4548a79dfa754b0ef8e2 |
| institution | Kabale University |
| issn | 1664-0640 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Psychiatry |
| spelling | doaj-art-5e398e01f99f4548a79dfa754b0ef8e22025-08-20T03:48:14ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-05-011610.3389/fpsyt.2025.15090931509093Human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brainBenedictor Alexander Nguchu0Benedictor Alexander Nguchu1Jing Zhao2Yu Lu3Yifei Han4Han Jin5Xiaoxiao Wang6Hongjun Li7Peter Shaw8Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaSchool of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaSchool of Electronic Engineering, Tianjin University of Technology and Education, Tianjin, ChinaCenter for Biomedical Imaging, University of Science and Technology of China, Hefei, Anhui, ChinaDepartment of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, Zhejiang, ChinaIntroductionExisting evidence indicates that HIV enters the nervous system in the early days of infection. However, the involvement of HIV in the pathogenesis of key biological aspects of the brain, such as glymphatic clearance and brain aging, and its role in explaining complex phenomena like motoric and executive dysfunction, remains unrecognized.MethodsHerein, we recruited 145 subjects to study the brain aging using brain-predicted age differences (brain-PADs) and investigate how HIV affects the typical trajectory of glymphatic clearance in aging brain. The assessment of glymphatic clearance in the aging brain was performed using a technique called "diffusion tensor image analysis along the perivascular space” (DTI-ALPS). We further evaluated the association between accelerated brain aging trajectories and cognitive performance to explain impairments observed in motor and executive functions in people living with HIV. ResultsOur results showed that subjects with HIV had increased brain-PAD in several brain structures compared to those who were HIV-negative, suggesting underlying neuropathology associated with HIV. The brain structures demonstrating accelerated aging (increased brain-PAD) include the middle frontal gyrus, pre-and post-central gyri, supramarginal gyrus, precuneus, cuneus, parietal lobule and operculum, and superior and middle occipital gyri of the left hemisphere. While normal subjects maintained typical trajectories of glymphatic clearance (as measured by the DTI-ALPS index) with age or brain-PADs for several structures, including the left central operculum, left frontal operculum, left opercular inferior frontal gyrus, and left triangular inferior frontal gyrus, none of these trajectories were maintained in subjects with HIV. Our data also show that increased brain-PAD in brain regions was associated with lower performance in motor and executive functions. DiscussionThese findings suggest that HIV infection accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain, which may explain the complex mechanisms underlying cognitive impairment in motor and executive domains often seen in HIV patients. These new insights may shift our understanding of HIV pathology and aid the development of new therapeutic targets, contrary to previous approaches.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1509093/fullHIV-infectionchronic inflammationaccelerated brain agingbrain predicted age differenceglymphatic clearance trajectoryDTI-ALPS index |
| spellingShingle | Benedictor Alexander Nguchu Benedictor Alexander Nguchu Jing Zhao Yu Lu Yifei Han Han Jin Xiaoxiao Wang Hongjun Li Peter Shaw Human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain Frontiers in Psychiatry HIV-infection chronic inflammation accelerated brain aging brain predicted age difference glymphatic clearance trajectory DTI-ALPS index |
| title | Human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain |
| title_full | Human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain |
| title_fullStr | Human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain |
| title_full_unstemmed | Human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain |
| title_short | Human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain |
| title_sort | human immunodeficiency virus accelerates brain aging and disrupts the trajectory of glymphatic clearance in aging brain |
| topic | HIV-infection chronic inflammation accelerated brain aging brain predicted age difference glymphatic clearance trajectory DTI-ALPS index |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1509093/full |
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