{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:05:35Z","timestamp":1789477535922,"version":"build-2803163510"},"reference-count":54,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100018537","name":"national science and technology major project","doi-asserted-by":"publisher","award":["2023ZD0504900; 2023ZD0504901"],"award-info":[{"award-number":["2023ZD0504900; 2023ZD0504901"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research","award":["2022-PUMCH-D-007"],"award-info":[{"award-number":["2022-PUMCH-D-007"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Our aim is to examine the interplay between cerebral small vessel disease (CSVD) pathology, Alzheimer\u2019s disease (AD) related amyloid-\u03b2 (A\u03b2) clearance, and cognition in general population. Cross-sectional structural equation modeling (SEM) was conducted to evaluate CSVD burden, cognition, and plasma A\u03b242\/40 ratios in 1026 participants without dementia from a prospective community-based cohort. CSVD burden was quantified using five established MRI markers, while cognition was assessed with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), verbal fluency test, and reverse digit span. Models were adjusted for age, sex, education, body mass index, vascular risk factors (hypertension, diabetes mellitus, hyperlipidemia, and smoking), antihypertensive medication use, and\n                    <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                    carrier status. Greater CSVD burden was significantly associated with poorer cognition (\n                    <jats:italic toggle=\"yes\">B<\/jats:italic>\n                    \u2009=\u2009\u22122.607\u2009\u00b1\u20091.016, \u03b2\u2009=\u2009\u22120.167,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.010), with white matter hyperintensity volume (\u2206\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.3%,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.016) and brain parenchymal fraction (\u2206\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.4%,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.019) contributing most strongly. CSVD burden was also negatively correlated with plasma A\u03b242\/40 ratios (\n                    <jats:italic toggle=\"yes\">B<\/jats:italic>\n                    \u2009=\u2009\u22120.280\u2009\u00b1\u20090.074, \u03b2\u2009=\u2009\u22120.140,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.001), which partially mediated the CSVD-cognition association (\n                    <jats:italic toggle=\"yes\">B<\/jats:italic>\n                    \u2009=\u2009\u22120.241\u2009\u00b1\u20090.087, \u03b2\u2009=\u2009\u22120.015,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.006). These findings underscore potential CSVD involvement in AD-related pathology across aging.\n                  <\/jats:p>","DOI":"10.1177\/0271678x261437577","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:20:42Z","timestamp":1775805642000},"page":"2261-2271","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cerebral small vessel disease burden relates to cognitive decline via impaired amyloid clearance in the general population"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1096-0168","authenticated-orcid":false,"given":"Chi-Heng","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Medicine, Anhui Province Key Laboratory of Biomedical Aging Research, Neurodegenerative Disorder Research Center, University of Science and Technology of China, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ni","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ying","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Li","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Yu","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Medicine, Anhui Province Key Laboratory of Biomedical Aging Research, Neurodegenerative Disorder Research Center, University of Science and Technology of China, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding-Ding","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Prevention and Early Intervention, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Cheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308426"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00131-X"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70124-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0b013e3182299496"},{"key":"e_1_3_3_7_2","first-page":"101284","article-title":"Middle-age cerebral small vessel disease and cognitive function in later life: a population-based prospective cohort study","volume":"55","author":"Siddiquee AT","year":"2025","unstructured":"Siddiquee AT, Hwang YH, Kim S, et al. Middle-age cerebral small vessel disease and cognitive function in later life: a population-based prospective cohort study. Lancet Reg Health West Pac 2025; 55: 101284.","journal-title":"Lancet Reg Health West Pac"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13607"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.670216"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.007146"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X241235494"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000245091.28429.6a"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30029-1"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51720"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000213438"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu393"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209665"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-3-267"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2017.02110"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2366"},{"key":"e_1_3_3_21_2","first-page":"36","article-title":"[The application of Montreal cognitive assessment in urban Chinese residents of Beijing]","volume":"47","author":"Wen H-B","year":"2008","unstructured":"Wen H-B, Zhang Z-X, Niu F-S, et al. [The application of Montreal cognitive assessment in urban Chinese residents of Beijing]. Zhonghua Nei Ke Za Zhi 2008; 47: 36\u201339.","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/23279095.2021.1961774"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3758\/s13428-018-1055-2"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.8903"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220834"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/00273171.2016.1245600"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209801"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008864"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.01.004"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19378"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.125.051564"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-025-03949-8"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03616-8"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202933"},{"key":"e_1_3_3_35_2","article-title":"The association between cerebral \u201cdirty-appearing\u201d white matter and progression of small vessel disease in community-dwelling older adults","volume":"2025","author":"Eiling I","year":"2025","unstructured":"Eiling I, Sigurdsson S, Verweg L, et al. The association between cerebral \u201cdirty-appearing\u201d white matter and progression of small vessel disease in community-dwelling older adults. J Cereb Blood Flow Metab 2025; 2025: 0271678X251385591.","journal-title":"J Cereb Blood Flow Metab"},{"key":"e_1_3_3_36_2","article-title":"Small vessel disease lesion type and brain atrophy: the role of co-occurring amyloid","volume":"12","author":"Heinen R","year":"2020","unstructured":"Heinen R, Groeneveld ON, Barkhof F, et al. Small vessel disease lesion type and brain atrophy: the role of co-occurring amyloid. Alzheimers Dement 2020; 12: e12060.","journal-title":"Alzheimers Dement"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.834496"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.044173"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.017526"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006079"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.031073"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00904-7"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.163822"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44319-3"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.05.020"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0250371"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X251355742"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.035674"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10091479"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.062181"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01296-5"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009240"},{"key":"e_1_3_3_53_2","first-page":"179","article-title":"Plasma amyloid \u03b2 42\/40 ratios as biomarkers for amyloid \u03b2 cerebral deposition in cognitively normal individuals","volume":"8","author":"Fandos N","year":"2017","unstructured":"Fandos N, P\u00e9rez-Grijalba V, Pesini P, et al. Plasma amyloid \u03b2 42\/40 ratios as biomarkers for amyloid \u03b2 cerebral deposition in cognitively normal individuals. Alzheimers Dement 2017; 8: 179\u2013187.","journal-title":"Alzheimers Dement"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49859-w"},{"key":"e_1_3_3_55_2","article-title":"Clinical correlates of perfusion and diffusion MRI metrics in cognitively unimpaired older adults","volume":"2025","author":"Shakibajahromi B","year":"2025","unstructured":"Shakibajahromi B, Dolui S, Brown CA, et al. Clinical correlates of perfusion and diffusion MRI metrics in cognitively unimpaired older adults. J Cereb Blood Flow Metab 2025; 2025: 0271678X251389043.","journal-title":"J Cereb Blood Flow Metab"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X261437577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X261437577","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X261437577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:23:53Z","timestamp":1789475033000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X261437577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":54,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1177\/0271678X261437577"],"URL":"https:\/\/doi.org\/10.1177\/0271678x261437577","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}