Cognitive impairment in patients with melanoma before adjuvant immune checkpoint inhibitor therapy and associations with brain gray matter, catechol-O-methyltransferase genotype, and psychological factors

Abstract

Background: Cancer-related cognitive impairment (CRCI) is a significant concern in patients with cancer but understanding its prevalence and risk factors in patients with malignant melanoma (MMPs) remains limited. This study explores CRCI via a multifaceted approach integrating neurobiological, genetic, and psychological assessments.

Methods: Cognitive functioning across multiple domains was assessed via neuropsychological tests in 47 MMPs before adjuvant immune checkpoint inhibitor therapy, compared with 53 matched healthy controls (HCs). Self-reported cognitive complaints, brain gray matter (GM) properties, catechol-O-methyltransferase (COMT) genotype, and psychological and behavioral factors were evaluated. Between-group differences were analyzed with t-tests and χ² tests, and associations were explored with correlation analyses. GM properties were assessed in a subset of 23 MMPs and 47 HCs.

Results: MMPs exhibited significantly lower cognitive functioning across multiple tests (all p < .05), with a high CRCI prevalence (68.1% vs. 26.4% in HCs). MMPs reported higher fatigue, anxiety, and insomnia severity and poorer sleep quality and quality of life (all p < .01). Self-reported cognitive complaints in MMPs were associated with some cognitive test scores (all p < .05), fatigue (p < .001), and anxiety (p = .045). GM analyses revealed a smaller left cuneus volume in MMPs and significant associations between MMPs' processing speed and cortical thickness (right precentral and left inferior parietal regions) and between delayed verbal memory and right postcentral GM volume (all p < .01).

Conclusions: These findings underscore the need for comprehensive assessments in MMPs to better understand and address CRCI. A multifaceted approach would provide valuable insights that could inform future interventions and improve patient outcomes and quality of life.

Keywords: cancer; cancer‐related cognitive impairment (CRCI); catechol‐O‐methyltransferase (COMT); magnetic resonance imaging; melanoma; psycho‐oncology; side effects.