{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:14:02Z","timestamp":1793369642619,"version":"4.5.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Although the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is widely utilized as a proxy for glymphatic function in Alzheimer's Disease (AD) research, its association with core AD pathological biomarkers remains inconclusive due to inter-study heterogeneity. This systematic review aimed to investigate associations between the DTI-ALPS index and AD biomarkers and to elucidate potential sources of heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study protocol adhered to PRISMA guidelines and was registered with PROSPERO (CRD420251266067). We systematically searched Web of Science, PubMed, and ScienceDirect from January 1, 2017 to September 18, 2025 for studies examining the relationship between the DTI-ALPS index and core AD biomarkers. Random-effects meta-analyses were conducted when studies employed comparable methodologies and reported effect sizes while narrative synthesis was performed otherwise. Methodological quality was assessed using the Newcastle\u2013Ottawa Scale (NOS) and the risk of bias was evaluated using the Risk of Bias in Systematic reviews (ROBIS) tool.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-six studies were included. Meta-analyses revealed significant correlations between the DTI-ALPS index (\n                      <jats:italic>N<\/jats:italic>\n                      = 22) and A\u03b2 PET deposition (\n                      <jats:italic>N<\/jats:italic>\n                      = 9), MMSE (\n                      <jats:italic>N<\/jats:italic>\n                      = 15), and MoCA (\n                      <jats:italic>N<\/jats:italic>\n                      = 10) scores. Conversely, the association with tau PET deposition (\n                      <jats:italic>N<\/jats:italic>\n                      = 3) was not significant after adjusting for publication bias. Regarding clinical staging, indices were significantly lower in AD and mild cognitive impairment groups compared to controls but no difference was found between the two patient groups. Based on meta-regression and narrative synthesis results, we identified methodological variability and AD pathological complexity as primary sources of heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Consequently, we proposed the \u201cGS Hub Integrative Framework.\u201d This framework posits that vascular, genetic, lifestyle, and environmental risk factors converge on glymphatic dysfunction (DTI-ALPS index) as a central hub, accelerating A\u03b2\/tau accumulation, neurodegeneration, and cognitive decline. Future methodological standardization and refined patient stratification are essential for clinical translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251266067<\/jats:ext-link>\n                      , identifier: CRD420251266067.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1832525","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:33:35Z","timestamp":1782970415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Glymphatic dysfunction in Alzheimer's disease: a systematic review and meta-analysis of the DTI-ALPS index as an imaging biomarker"],"prefix":"10.3389","volume":"18","author":[{"given":"Yutong","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Adolescent CyberPsychology and Behavior (CCNU), Ministry of Education","place":["Wuhan, China"]},{"name":"Key Laboratory of Human Development and Mental Health of Hubei Province, School of Psychology, Central China Normal University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Engineering, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adolescent CyberPsychology and Behavior (CCNU), Ministry of Education","place":["Wuhan, China"]},{"name":"Key Laboratory of Human Development and Mental Health of Hubei Province, School of Psychology, Central China Normal University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Chemistry and Life Science, Beijing University of Technology","place":["Beijing, China"]},{"name":"Intelligent Physiological Measurement and Clinical Translation, Beijing International Base for Scientific and Technological Cooperation, Beijing University of Technology","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adolescent CyberPsychology and Behavior (CCNU), Ministry of Education","place":["Wuhan, China"]},{"name":"Key Laboratory of Human Development and Mental Health of Hubei Province, School of Psychology, Central China Normal University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenrong","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adolescent CyberPsychology and Behavior (CCNU), Ministry of Education","place":["Wuhan, China"]},{"name":"Key Laboratory of Human Development and Mental Health of Hubei Province, School of Psychology, Central China Normal University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adolescent CyberPsychology and Behavior (CCNU), Ministry of Education","place":["Wuhan, China"]},{"name":"Key Laboratory of Human Development and Mental Health of Hubei Province, School of Psychology, Central China Normal University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100395","DOI":"10.1016\/j.cccb.2025.100395","article-title":"Disentangling the contributions of cerebrovascular-related white matter integrity markers to cognitive aging","volume":"9","author":"Agah","year":"2025","journal-title":"Cereb. 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