Role of Oxidative Stress in Microvascular Dysfunction and Early Neurocognitive Changes

Abstract

Background: Oxidative stress plays a significant role in endothelial damage, microcirculatory dysfunction and early cognitive dysfunction. Further clinical assessment is needed to determine its associations with microvascular dysfunction and subtle cognitive changes.

Objective: To assess the association of oxidative stress biomarkers with microvascular dysfunction and early neurocognitive changes among adults with cardiovascular risk factors.

Methods: This prospective observational study was conducted from June 2024 to June 2025 at the Department of Medicine, Indus Medical College, Tando Muhammad Khan, Pakistan, in collaboration with the Department of Psychiatry, Lady Reading Hospital–Medical Teaching Institution, Peshawar, Pakistan. One hundred and twenty cardiovascular risk factor adults (40-70 years) were recruited. Oxidative stress markers, inflammatory markers, microvascular markers and neurocognitive function were measured. Data were analyzed using correlation and multivariable regression analysis.

Results: Microvascular dysfunction was observed in 71 participants (59.2%). The malondialdehyde, oxidized LDL, hs-CRP, and interleukin-6 levels were significantly higher and total antioxidant capacity, superoxide dismutase, and catalase levels were significantly lower in these participants. They also had decreased flow-mediated dilatation, longer capillary refill time, higher retinal microvascular abnormalities, and lower cognitive scores. Microvascular dysfunction was associated with early neurocognitive change. The factors independently associated with early change in neurocognition were elevated malondialdehyde, oxidized LDL, reduced flow-mediated dilation, and retinal microvascular abnormality.

Conclusion: There is a very significant relationship between oxidative stress, microvascular dysfunction and early neurocognitive decrease. The early detection of oxidative and microvascular markers may be useful in identifying individuals at risk for vascular cognitive impairment.