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Alzheimer\u2019s disease (AD) pathologies co-existing with cerebral small vessel disease (CSVD) is the most common pathogenesis for dementia. We hypothesize that AD pathologies and CSVD could be associated with glymphatic dysfunction, contributing to cognitive impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Participants completed with amyloid PET, diffusion tensor imaging (DTI), and T2 fluid-attenuated inversion-recovery (FLAIR) sequences were included from the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI). White matter hyperintensities (WMH), the most common CSVD marker, was evaluated from T2FLAIR images and represented the burden of CSVD. Amyloid PET was used to assess A\u03b2 aggregation in the brain. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, the burden of\u00a0enlarged perivascular spaces (PVS), and choroid plexus volume to reflect glymphatic function. The relationships between WMH burden\/A\u03b2 aggregation and these glymphatic markers as well as the correlations between glymphatic markers and cognitive function were investigated. Furthermore, we conducted mediation analyses to explore the potential mediating effects of glymphatic markers in the relationship between WMH burden\/A\u03b2 aggregation and cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One hundred and thirty-three participants along the AD continuum were included, consisting of 40 CN\u2009\u2212\u2009, 48 CN\u2009+\u2009, 26 MCI\u2009+\u2009, and 19 AD\u2009+\u2009participants. Our findings revealed that there were negative associations between whole-brain A\u03b2 aggregation (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2212\u20090.249,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022) and WMH burden (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2212\u20090.458,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) with DTI-ALPS. Additionally, A\u03b2 aggregation (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.223,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.041) and WMH burden (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.294,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006) were both positively associated with choroid plexus volume. However, we did not observe significant correlations with PVS enlargement severity. DTI-ALPS was positively associated with memory (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.470, FDR-\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), executive function (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.358, FDR-\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), visual-spatial (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.223, FDR-\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.040), and language (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.419, FDR-\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Conversely, choroid plexus volume showed negative correlations with memory (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2212\u20090.315, FDR-\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), executive function (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2212\u20090.321, FDR-\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), visual-spatial (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2212\u20090.233, FDR-\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031), and language (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2009\u2212\u20090.261, FDR-\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.021). There were no significant correlations between PVS enlargement severity and cognitive performance. In the mediation analysis, we found that DTI-ALPS acted as a mediator in the relationship between WMH burden\/A\u03b2 accumulation and memory and language performances.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study provided evidence that both AD pathology (A\u03b2) and CSVD were associated with glymphatic dysfunction, which is further related to cognitive impairment. These results may provide a theoretical basis for new targets for treating AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13195-024-01407-w","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T06:02:38Z","timestamp":1708408958000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer\u2019s disease continuum participants"],"prefix":"10.1186","volume":"16","author":[{"given":"Hui","family":"Hong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luwei","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingze","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaicheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeerfan","family":"Jiaerken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfeng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"issue":"11","key":"1407_CR1","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","volume":"17","author":"MK Rasmussen","year":"2018","unstructured":"Rasmussen MK, Mestre H, Nedergaard M. 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