Oxidative Stress Biomarkers as Preclinical Markers of Mild Cognitive Impairment: The Impact of Age and Sex

<b>Background:</b> Reactive oxygen species (ROS) are involved in the pathophysiology of neurodegeneration and cognitive decline, indicating the potential use of oxidative stress biomarkers for early diagnosis. Mild cognitive impairment (MCI) is defined as a cognitive decline beyond normal aging, without significant impact on daily functioning, and is considered an important stage of early detection of neurodegeneration. This study aimed to investigate serum and cerebrospinal fluid (CSF) levels of oxidative stress biomarkers, total ROS and malondialdehyde (MDA) in patients with MCI to evaluate their utility in the early diagnosis of Alzheimer's disease (AD). Levels of oxidative stress biomarkers were also assessed according to age and sex, as well as their correlation with the established CSF biomarkers, including amyloid-beta (Aβ40, Aβ42 and Aβ42/Aβ40 ratio), phosphorylated tau protein (p-tau) and total tau (t-tau). <b>Methods:</b> A total of 114 adults were divided into three groups: MCI (A-) patients with a normal CSF Aβ42/Aβ40 ratio (<i>n</i> = 38), MCI (A+) patients with an abnormal Aβ42/Aβ40 ratio (<i>n</i> = 38) and healthy cognitive function individuals with a normal Aβ42/Aβ40 ratio (<i>n</i> = 38). Established CSF biomarkers were conducted using an automated immunochemical method, while total ROS levels were measured by fluorometry and MDA levels were determined by competitive inhibition enzyme immunoassay. <b>Results:</b> A statistically significant difference was observed in CSF MDA levels (<i>p</i> < 0.05) and serum ROS levels (<i>p</i> < 0.05) between the study groups. Sex analysis revealed significantly higher levels of CSF MDA levels in the MCI (A+) males' group (<i>p</i> < 0.05). In terms of age categorization, serum MDA levels were markedly higher in the MCI (A+) group of older patients (<i>p</i> < 0.01). <b>Conclusions:</b> These findings highlight the importance of individualized approaches, including investigation of oxidative stress biomarkers profile to prevent and manage individuals in the early stages of MCI, considering demographic factors.