Regulation of Blood-Brain Barrier Permeability by APOE Gene Polymorphism and Its Impact on Cognitive Function Post-Radiotherapy in Nasopharyngeal Carcinoma: An MRI Study

Study on the Regulation of Blood-Brain Barrier Permeability by APOE Gene Polymorphism and Its Impact on Cognitive Function After Radiotherapy for Nasopharyngeal Carcinoma: An MRI Investigation

adiotherapy-induced cognitive dysfunction is a severe complication following radiotherapy for nasopharyngeal carcinoma (NPC). Our previous studies have demonstrated that abnormalities in brain function and structural connectivity after radiotherapy play a significant role in the occurrence of radiation-induced cognitive dysfunction. However, the key risk factors and underlying neural mechanisms remain unclear. Research has shown that increased blood-brain barrier (BBB) permeability after radiotherapy is an important mechanism leading to cognitive dysfunction, and different APOE gene subtypes can regulate BBB permeability. Therefore, APOE gene polymorphisms are likely to influence post-radiotherapy vascular barrier permeability in NPC patients, thereby affecting their brain function and structural connectivity changes, and ultimately impacting their cognitive function.

This project aims to establish a longitudinal brain imaging database for NPC patients with different APOE genotypes before and after radiotherapy, based on previous research findings. The project will integrate dynamic contrast-enhanced MRI (DCE-MR), resting-state functional MRI (fMRI), and diffusion spectrum imaging (DSI) techniques. By comparing DCE-derived metrics across different genotype groups, the study seeks to identify brain regions with BBB damage differences between APOE genotype groups before and after radiotherapy. Furthermore, it will investigate how BBB damage in these brain regions mediates functional and structural connectivity abnormalities, and their relationship with radiation-induced cognitive dysfunction. The goal is to clarify the neural regulation mechanism of APOE gene polymorphisms in radiation-induced cognitive dysfunction and to identify risk factors for radiation-induced cognitive dysfunction. This research will provide a theoretical basis and valuable reference for the individualized prevention and treatment of radiation-induced cognitive dysfunction.

Inclusion Criteria:

Patients newly diagnosed with nasopharyngeal carcinoma, pathologically confirmed, and who have not received anti - tumor treatments such as surgery, induction chemotherapy, or radiotherapy.

All patients are of Han ethnicity and right - handed. Patients are aged between 20 and 60 years old, with an educational level of junior high school or above.

The clinical stage of the included patients is AJCC 8th edition stage I - IVa, without distant metastasis, and patients are scheduled to receive intensity - modulated radiotherapy (IMRT) according to the clinical plan.

Patients have no other serious systemic diseases except nasopharyngeal carcinoma.

There is no intracranial invasion of nasopharyngeal carcinoma. Routine MRI examinations (including T1WI, T2WI, and FLAIR) are negative. The baseline basic cognitive assessment scales (MoCA and MMSE) before radiotherapy are normal.

Patients have no family history of mental illness. Patients have no history of neurological diseases or head trauma. After fully understanding the experimental content, the subjects agree to participate in this project and sign the informed consent form

Exclusion Criteria:

Patients diagnosed with Alzheimer's disease (AD) before being included. AD is diagnosed by psychiatrists according to the 9th Revision of the International Classification of Diseases, Clinical Modification (ICD - 9 - CM).

Patients with intracranial lesions detected by routine MRI examinations. Patients with contraindications to magnetic resonance examinations. Patients with concurrent other diseases. Patients with tumor recurrence who need re - radiotherapy, or those who cannot adhere to and complete IMRT treatment.

Left - handed or ambidextrous patients. Patients with a history of head trauma or mental/neurological diseases. Patients aged less than 20 or more than 60 years old. Patients with serious systemic diseases such as heart, lung, or kidney diseases.

Patients with diabetes or hypertension. Patients who cannot cooperate to complete the neurocognitive scale tests.