Abstract

Background: Whole-brain radiotherapy (WBRT) remains a common treatment for patients with brain metastases from non-small cell lung cancer (NSCLC). As overall survival improves, late toxicities such as cognitive decline are receiving increasing clinical attention. This study aimed to assess the degree of cognitive impairment following WBRT and identify associated clinical factors.

Methods: A prospective cohort study was conducted on 61 patients with brain metastases from NSCLC who received WBRT at Military Hospital 175 between May 2024 and May 2025. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) at four time points: before WBRT, and at 2, 4, and 6 months post-treatment. Associations between cognitive decline and clinical factors were analyzed.

Results: The mean MMSE score declined progressively over time, from 27.11 ± 1.97 at baseline to 22.30 ± 2.67 at 6 months (p < 0.001). At 4 months, hippocampal metastasis (p = 0.04), absence of memantine use (p = 0.03), and intracranial progression (p = 0.03) were significantly associated with cognitive decline. Memantine demonstrated a clear protective effect at 6 months (p < 0.01).

Conclusions: WBRT induces progressive cognitive decline in patients with NSCLC and brain metastases. The use of memantine shows initial potential in preserving cognitive function. Routine cognitive assessment and individualized treatment strategies should be implemented in clinical practice.