Reyes Anny, Stasenko Alena, Hopper Austin, Kohli Jiwandeep S, Helm Jonathan L, Salans Mia, Prabhakaran Divya, Kamalyan Lily, Wilkinson Molly, Unnikrishnan Soumya, Karunamuni Roshan, Hattangadi-Gluth Jona, McDonald Carrie R
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California, USA.
Department of Psychiatry, University of California San Diego, La Jolla, California, USA.
Neuro Oncol. 2025 Feb 10;27(2):466-478. doi: 10.1093/neuonc/noae183.
Patients with primary brain tumors demonstrate heterogeneous patterns of cognitive dysfunction, which we explore using latent profile analysis to identify cognitive phenotypes and their trajectories in patients receiving radiotherapy (RT).
Ninety-six patients completed neuropsychological testing before and post-RT (3, 6, and 12 months) on a prospective longitudinal trial, including measures of processing speed, executive function, language, and verbal and visual memory. Models with 2-4 classes were examined. Demographic and clinical data were examined across phenotypes and post-RT cognitive change was evaluated.
The optimal model identified 3 unique cognitive phenotypes including a group of patients with generalized impairments (11.5%), a group with isolated verbal memory impairments (21.9%), and a group with minimal impairments (66.7%). The Verbal Memory phenotype had fewer years of education (P = .007) and a greater proportion of males (P < .001); the Generalized group had a greater proportion of patients with IDH-wild type gliomas and showed greater symptoms of anxiety and poorer quality of life (P-values < .05); and the Minimal Impairment phenotype had higher rates of IDH-Mutant gliomas. Approximately 50% of patients declined on at least one cognitive domain with memory being the most vulnerable. Patients who declined reported greater symptoms of depression (P = .007) and poorer quality of life (P = .025).
We identified 3 distinct cognitive phenotypes in patients with primary brain tumors receiving RT, each associated with unique demographic and clinical (eg, IDH mutational status) profiles, with mood symptoms associated with late cognitive decline. This patient-centered approach enhances our understanding of clinical profiles associated with cognitive dysfunction and treatment-related neurotoxicity.
原发性脑肿瘤患者表现出异质性的认知功能障碍模式，我们使用潜在类别分析来探索这些模式，以识别接受放疗（RT）患者的认知表型及其发展轨迹。
96名患者在一项前瞻性纵向试验中于放疗前后（3、6和12个月）完成了神经心理学测试，包括处理速度、执行功能、语言以及言语和视觉记忆的测量。研究了具有2 - 4个类别的模型。对不同表型的人口统计学和临床数据进行了检查，并评估了放疗后认知变化。
最佳模型识别出3种独特的认知表型，包括一组有广泛性损伤的患者（11.5%）、一组有孤立性言语记忆损伤的患者（21.9%）和一组有轻微损伤的患者（66.7%）。言语记忆表型的患者受教育年限较少（P = 0.007），男性比例较高（P < 0.001）；广泛性损伤组中异柠檬酸脱氢酶（IDH）野生型胶质瘤患者比例较高，且焦虑症状更严重，生活质量较差（P值 < 0.05）；轻微损伤表型中IDH突变型胶质瘤的发生率较高。约50%的患者在至少一个认知领域出现下降，其中记忆最为脆弱。认知下降的患者报告有更严重的抑郁症状（P = 0.007）和较差的生活质量（P = 0.025）。
我们在接受放疗的原发性脑肿瘤患者中识别出3种不同的认知表型，每种表型都与独特的人口统计学和临床（如IDH突变状态）特征相关，情绪症状与晚期认知下降有关。这种以患者为中心的方法增强了我们对与认知功能障碍和治疗相关神经毒性相关的临床特征的理解。
