{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T06:08:15Z","timestamp":1794031695274,"version":"4.8.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"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>Background<\/jats:title>\n                    <jats:p>The relationship between white matter hyperintensities (WMH) and the core features of Alzheimer\u2019s disease (AD) remains controversial. Further, due to the prevalence of co-pathologies, the precise role of WMH in cognition and neurodegeneration also remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Herein, we analyzed 1803 participants with available WMH volume data, extracted from the ADNI database, including 756 cognitively normal controls, 783 patients with mild cognitive impairment (MCI), and 264 patients with dementia. Participants were grouped according to cerebrospinal fluid (CSF) pathology (A\/T profile) severity. Linear regression analysis was applied to evaluate the factors associated with WMH volume. Modeled by linear mixed-effects, the increase rates (\u0394) of the WMH volume, cognition, and typical neurodegenerative markers were assessed. The predictive effectiveness of WMH volume was subsequently tested using Cox regression analysis, and the relationship between WMH\/\u0394WMH and other indicators such as cognition was explored through linear regression analyses. Furthermore, we explored the interrelationship among amyloid-\u03b2 deposition, cognition, and WMH using mediation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Higher WMH volume was associated with older age, lower CSF amyloid-\u03b2 levels, hypertension, and smoking history (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.001), as well as cognitive status (MCI,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001; dementia,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008), but not with CSF tau levels. These results were further verified in any clinical stage, except hypertension and smoking history in the dementia stage. Although WMH could not predict dementia conversion, its increased levels at baseline were associated with a worse cognitive performance and a more rapid memory decline. Longitudinal analyses showed that baseline dementia and positive amyloid-\u03b2 status were associated with a greater accrual of WMH volume, and a higher \u0394WMH was also correlated with a faster cognitive decline. In contrast, except entorhinal cortex thickness, the WMH volume was not found to be associated with any other neurodegenerative markers. To a lesser extent, WMH mediates the relationship between amyloid-\u03b2 and cognition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WMH are non-specific lesions that are associated with amyloid-\u03b2 deposition, cognitive status, and a variety of vascular risk factors. Despite evidence indicating only a weak relationship with neurodegeneration, early intervention to reduce WMH lesions remains a high priority for preserving cognitive function in the elderly.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2024.1412735","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T10:07:58Z","timestamp":1726135678000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Association of white matter hyperintensities with cognitive decline and neurodegeneration"],"prefix":"10.3389","volume":"16","author":[{"given":"Tao-Ran","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai-Le","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Ran","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-Shan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Qi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"103383","DOI":"10.1016\/J.Nicl.2023.103383","article-title":"The association between white matter Hyperintensities and amyloid and tau deposition","volume":"38","author":"Alban","year":"2023","journal-title":"Neuroimage Clin."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/S13195-023-01243-4","article-title":"Arterial hypertension and \u0392-amyloid accumulation have spatially overlapping effects on posterior white matter Hyperintensity volume: a cross-sectional study","volume":"15","author":"Bernal","year":"2023","journal-title":"Alzheimers Res. 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