Key result
Higher GFAP and lower Aβ42/40 ratio are linked to greater perivascular space burden in VCI.
Why the study?
Plasma-based biomarkers like GFAP and the Aβ42/40 ratio are understudied in vascular cognitive impairment, an underdiagnosed cause of cognitive decline.
Do plasma GFAP and Aβ42/40 ratio track with perivascular space burden and domain-specific cognitive decline in vascular cognitive impairment?
Cross-Sectional (n=108)
Do plasma GFAP and Aβ42/40 ratio track with perivascular space burden and domain-specific cognitive decline in vascular cognitive impairment?
Odds Ratio: 0.00111
p-value: p=0.0438
Elevated GFAP and a low Aβ42/40 ratio indicate greater perivascular space burden and correlate with specific cognitive domain deficits, suggesting potential utility in stratifying vascular cognitive impairment.
May support biomarker stratification in vascular cognitive impairment; leaves open prospective validation and clinical utility.
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.
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Wang et al. (2025) conducted a cross-sectional in Vascular Cognitive Impairment (n=108). Elevated plasma GFAP and reduced Aβ42/40 ratio was evaluated on Perivascular space (PVS) grade (OR 0.00111, p=0.0438). Higher GFAP and a lower Aβ42/40 ratio were significantly correlated with a higher perivascular space burden in patients with vascular cognitive impairment.
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