1. Introduction

Cerebrovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) are among the most pressing global health challenges due to their high prevalence, mortality rates, and socio-economic burdens. CVDs are the third leading cause of death and disability globally, following cardiovascular and oncological conditions, and are characterized by their significant morbidity and long-term consequences such as cognitive decline and physical incapacitation [1,2]. Concurrently, T2DM has emerged as a widespread chronic disease, notable for its systemic complications that include vascular, neurological, and metabolic disturbances [3].

The intersection between CVDs and T2DM is a critical area of study due to their shared pathophysiological pathways. T2DM exacerbates the risk of cerebrovascular damage through mechanisms such as chronic hyperglycemia, oxidative stress, endothelial dysfunction, and vascular inflammation [4,5]. This interplay significantly heightens the likelihood of developing cognitive dysfunction, which diminishes the quality of life and affects daily functioning [6].

Globally, the burden of T2DM continues to rise, with estimates suggesting a prevalence of over 500 million cases by 2030 [7]. Among these, a substantial proportion are expected to develop cerebrovascular complications, particularly chronic brain ischemia and cognitive dysfunction. Studies indicate that cognitive dysfunction in T2DM patients is often underdiagnosed and inadequately managed, despite its profound impact on patient outcomes [8].

In Uzbekistan, T2DM prevalence mirrors global trends, particularly affecting individuals in their economically productive years. This has spurred interest in identifying early diagnostic markers to mitigate its complications. Blood-brain barrier (BBB) integrity and intercellular adhesion molecules (e.g., ICAM-1) have emerged as promising indicators of cerebrovascular health and cognitive dysfunction [9]. These markers may offer insights into the progression of vascular and neurological damage in T2DM patients [10].

Despite advancements in understanding the pathophysiology of T2DM and CVD, gaps remain in early diagnostic strategies and preventive approaches. This study aims to address these gaps by evaluating the significance of BBB integrity and intercellular adhesion molecules in the development of cognitive dysfunction among T2DM patients. The findings are expected to contribute to enhanced screening protocols and targeted interventions, improving patient outcomes and reducing the socio-economic burden of these interlinked conditions.

The purpose of the study. The study aims to identify the role of blood-brain barrier integrity and vascular inflammation in cognitive dysfunction among type 2 diabetes mellitus patients. By exploring biomarkers like ICAM-1, it seeks to enhance early diagnosis and targeted interventions to improve patient outcomes.

2. Material and Method

Study Design and Population

This study was conducted over three years (2020-2023) at the Bukhara Regional Endocrinology Dispensary and the private medical center “Azizmed Shifo.” A total of 177 participants were recruited and categorized into three groups:

• Main Group (n=117): Comprised of T2DM patients with concurrent cerebrovascular pathologies. These patients exhibited varying degrees of cognitive dysfunction.

• Comparative Group (n=60): Included patients diagnosed with cerebrovascular pathologies but without T2DM. This group served to isolate the influence of diabetes on cerebrovascular outcomes.

• Control Group (n=20): Consisted of healthy volunteers with no history of T2DM or cerebrovascular conditions. They were included to establish baseline data for comparison.

Assessment Tools and Procedures

1. Neuropsychological Testing: Neuropsychological tests were administered to assess cognitive function. These included:

ο Mini-Mental State Examination (MMSE): A tool for evaluating overall cognitive status.

ο Montreal Cognitive Assessment (MoCA): Used to detect mild cognitive impairment.

ο Hospital Anxiety and Depression Scale (HADS): To measure anxiety and depression levels, which often co-occur with cognitive dysfunction.

2. Laboratory and Biochemical Analysis: Blood samples were analyzed for key markers, including:

ο Glycated Hemoglobin (HbA1c): An indicator of long-term glycemic control.

ο Intercellular Adhesion Molecule-1 (ICAM-1): A biomarker linked to vascular inflammation and BBB integrity.

3. Statistical Analysis: The data were analyzed using SPSS software. Correlation and regression analyses were performed to identify relationships between cognitive dysfunction severity and biomarker levels. Statistical significance was set at p < 0.05.

3. Research Result

Demographics and Clinical Characteristics

The study population comprised 97 females and 80 males, with an average age of 58 years (± 6.5). The prevalence of elevated HbA1c levels (>7.5%) was significantly higher in the main group (T2DM patients) compared to the comparative group. Notably, T2DM patients showed greater clinical variability in cognitive function and cerebrovascular markers.

Cognitive Dysfunction and Its Correlation with Biomarkers

1. Prevalence of Cognitive Dysfunction:

ο Approximately 68% of T2DM patients exhibited mild to moderate cognitive dysfunction.

ο Cognitive dysfunction severity was positively correlated with markers of chronic brain ischemia and vascular inflammation (p < 0.05).

2. ICAM-1 Levels and BBB Integrity:

ο Elevated ICAM-1 levels were detected in 78% of T2DM patients with cognitive dysfunction, compared to 45% in the comparative group.

ο A strong positive correlation (r = 0.72) was observed between ICAM-1 levels and cognitive dysfunction severity, highlighting the biomarker’s predictive value.

3. Statistical Analysis Results:

ο Regression analyses demonstrated that HbA1c and ICAM-1 levels independently predicted cognitive decline in T2DM patients. These biomarkers accounted for approximately 62% of the variability in cognitive scores.

4. Discussion

Pathophysiological Insights

The study's findings reinforce the critical role of blood-brain barrier (BBB) integrity and vascular inflammation in the development of cognitive dysfunction among T2DM patients. Elevated levels of ICAM-1 were strongly correlated with the severity of cognitive decline, emphasizing their importance as biomarkers for cerebrovascular damage. The results suggest that BBB disruption facilitates the infiltration of inflammatory mediators and subsequent neuronal damage, leading to chronic cerebral ischemia. This aligns with prior research indicating that chronic hyperglycemia, oxidative stress, and endothelial dysfunction are primary contributors to T2DM-related cognitive impairment. Additionally, the interaction between vascular inflammation and neuronal apoptosis creates a vicious cycle that exacerbates cognitive dysfunction.

The findings also highlight the potential of using ICAM-1 as an early indicator of cognitive decline in clinical settings. By monitoring this biomarker, healthcare providers can identify high-risk patients and implement preventive interventions before the onset of significant cognitive impairments. These interventions may include stringent glycemic control, anti-inflammatory therapies, and lifestyle modifications such as increased physical activity and dietary adjustments.

Clinical Implications

The study underscores the importance of integrating cognitive assessments into routine diabetes care. Neuropsychological tools such as MMSE and MoCA can help detect early signs of cognitive decline, facilitating timely intervention. Furthermore, the identification of ICAM-1 as a reliable biomarker opens new avenues for targeted therapeutic approaches. Anti-inflammatory agents that specifically address vascular inflammation could potentially slow the progression of cognitive dysfunction. Additionally, the results support the development of personalized treatment plans based on individual risk profiles, combining pharmacological and non-pharmacological strategies to optimize outcomes.

Limitations and Future Directions

Despite its strengths, this study has several limitations. The cross-sectional design restricts the ability to establish causal relationships between biomarkers and cognitive dysfunction. Longitudinal studies are needed to confirm the predictive value of ICAM-1 and explore its role in the progression of cerebrovascular complications. Moreover, the study's regional focus limits the generalizability of the findings. Expanding the research to include diverse populations and larger sample sizes would provide a more comprehensive understanding of the underlying mechanisms.

Future research should also investigate the therapeutic potential of interventions targeting BBB integrity and vascular inflammation. For instance, exploring the effects of ICAM-1 inhibitors or novel anti-inflammatory agents could yield valuable insights into treatment efficacy. Additionally, studies examining the interplay between other biomarkers, such as cytokines and oxidative stress markers, may uncover new pathways involved in T2DM-related cognitive decline.

5. Conclusions

This study highlights the pivotal role of BBB integrity and intercellular adhesion molecules in the development of cognitive dysfunction among T2DM patients. Elevated ICAM-1 levels serve as a critical biomarker, offering both diagnostic and prognostic utility. By addressing the underlying vascular and inflammatory mechanisms, targeted interventions can mitigate the cognitive and cerebrovascular burden of T2DM, thereby improving the overall quality of life and functional independence of affected individuals.