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Associations Between GFAP, Aβ42/40 Ratio, and Perivascular Spaces and Cognitive Domains in Vascular Cognitive Impairment

Year: 2025

Type: article

Abstract: 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 β42/40 (Aβ42/40) 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’s, 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 <26, along with the presence of confluent white matter hyperintensities (deep white matter hyperintensities score >2 or periventricular hyperintensities >3), and >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 Aβ42/40 ratio <0.05 and GFAP >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 Aβ42/40 ratio (p < 0.01) were correlated with a higher PVS grade. In the subgroup with a low Aβ42/40 ratio, a greater PVS burden was associated with poorer executive function (p = 0.045, β = 0.612), while in those with high GFAP levels, it was linked to more pronounced impairments in learning and memory (p = 0.006, β = 0.375). A lower Aβ42/40 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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26083541

Authors: Jia Dong James Wang, Yi Jin Leow, Ashwati Vipin, Gurveen Kaur Sandhu, Nagaendran Kandiah

Institutions: Nanyang Technological University, National University of Singapore, Duke-NUS Medical School, National Healthcare Group

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499