{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:57:32Z","timestamp":1793044652283,"version":"4.5.0"},"reference-count":17,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Strategic Academic Initiative","award":["SP1CLNT900-NTU-A630-PJ-03INP001400A630OOE01"],"award-info":[{"award-number":["SP1CLNT900-NTU-A630-PJ-03INP001400A630OOE01"]}]},{"name":"Nanyang Technological University","award":["SP1CLNT900-NTU-A630-PJ-03INP001400A630OOE01"],"award-info":[{"award-number":["SP1CLNT900-NTU-A630-PJ-03INP001400A630OOE01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perivascular spaces (PVS) support metabolic clearance in the brain and are increasingly recognized as key contributors to dementia pathogenesis. Plasma-based biomarkers, such as glial fibrillary acidic protein (GFAP) and the amyloid \u03b242\/40 (A\u03b242\/40) ratio, show promise in dementia diagnosis but remain understudied in vascular cognitive impairment (VCI). VCI, a major global cause of cognitive decline, may be more prevalent in Southeast Asia. Despite its impact, it is underdiagnosed compared to Alzheimer\u2019s, highlighting the need for early, reliable markers. This study aims to examine how these biomarkers relate to PVS burden and domain-specific cognitive outcomes in VCI. VCI was defined as global cognition as assessed by a Montreal Cognitive Assessment Score &lt;26, along with the presence of confluent white matter hyperintensities (deep white matter hyperintensities score &gt;2 or periventricular hyperintensities &gt;3), and &gt;1 lacuna. A total of 108 participants (mean age of 67.3 years, 51.9% female) were included. Multivariate ordinal regression assessed biomarker associations with PVS grade, adjusting for age and diastolic blood pressure. A A\u03b242\/40 ratio &lt;0.05 and GFAP &gt;54.1 pg\/mL were used as biomarker thresholds to subgroup the participants, and the relationship between these thresholds and cognitive performance was analyzed. Elevated GFAP (p = 0.0438) and a reduced A\u03b242\/40 ratio (p &lt; 0.01) were correlated with a higher PVS grade. In the subgroup with a low A\u03b242\/40 ratio, a greater PVS burden was associated with poorer executive function (p = 0.045, \u03b2 = 0.612), while in those with high GFAP levels, it was linked to more pronounced impairments in learning and memory (p = 0.006, \u03b2 = 0.375). A lower A\u03b242\/40 ratio and higher GFAP levels track greater PVS burden in VCI. PVS severity may be associated with domain-specific cognitive decline, highlighting the potential utility of these biomarkers in refining clinical assessments and monitoring disease progression.<\/jats:p>","DOI":"10.3390\/ijms26083541","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T12:05:56Z","timestamp":1744200356000},"page":"3541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Associations Between GFAP, A\u03b242\/40 Ratio, and Perivascular Spaces and Cognitive Domains in Vascular Cognitive Impairment"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0400-6999","authenticated-orcid":false,"given":"Jia Dong James","family":"Wang","sequence":"first","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3661-4816","authenticated-orcid":false,"given":"Yi Jin","family":"Leow","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3575-7287","authenticated-orcid":false,"given":"Ashwati","family":"Vipin","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurveen Kaur","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9244-4298","authenticated-orcid":false,"given":"Nagaendran","family":"Kandiah","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"},{"name":"Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore"},{"name":"National Healthcare Group, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41582-020-0312-z","article-title":"Perivascular spaces in the brain: Anatomy, physiology and pathology","volume":"16","author":"Wardlaw","year":"2020","journal-title":"Nat. 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