Longitudinal Analysis of Depression and Anxiety Symptoms as Independent Predictors of Neurocognitive Function: Prospective Trial of Brain Tumor Patients Receiving Radiotherapy [RT

Abstract

Brain tumor patients commonly experience depression and anxiety. In other neurologic conditions (e.g. Huntington’s) these symptoms are associated with neurocognitive decline. Since neurocognitive function is a critical outcome for brain tumor patients, we hypothesized that increased depression and anxiety symptoms will be independently associated with worsened neurocognition after brain RT. On a prospective trial, 54 primary brain tumor patients receiving brain RT underwent comprehensive neurocognitive evaluation prior to and at 3, 6, and 12 months post-RT. Attention/processing speed was assessed with Delis Kaplan Executive Function Trail Making Test [DKEFS TMT] and Wechsler Adult Intelligence Scale IV [WAIS-IV], executive functioning with DKEFS Verbal Fluency [DKEFS VF] and Wisconsin Card Sort Test [WCST], and memory with Hopkins Verbal Learning Test [HVLT] and Brief Visuospatial Memory Test Revised [BVMT-R]. Patients also completed the Beck Anxiety Inventory [BAI] and Beck Depression Inventory-II [BDI] at each time point, where higher scores reflect a greater number of symptoms. Associations between baseline BAI and BDI scores and covariates (age, sex, highest education level, tumor characteristics, chemotherapy, antiepileptic use, history of anxiety or depression) were assessed by independent samples t-test, one-way ANOVA, and Pearson correlations. Univariable and stepwise multivariable linear mixed-effects [LME] models assessed BAI and BDI as longitudinal predictors of neurocognitive t-scores. Statistical significance was set at α<0.05. Patients with a history of depression had higher baseline BDI scores (p= 0.011). Female sex (p=0.048) and high school education level (p=0.036) were associated with higher baseline BAI scores. Higher BAI was associated with decline in attention/processing speed on univariable LME: DKEFS TMT Visual Scanning (p=0.003), Number Sequencing (p=0.011), and Letter Sequencing (p<0.001). This remained significant on multivariable analyses for all 3 tests, p<0.001, p=0.011, and p=0.003, respectively. Higher BDI was associated with decline in DKEFS TMT Letter Sequencing in univariable (p=0.002) and multivariable (p=0.013) models. Increased BAI was associated with poorer BVMT Delayed Recall memory in univariable (p=0.012) but not multivariable (p=0.383) models. Increased BDI was associated with decline in executive functioning in DKEFS VF Category Switching univariable (p=0.031) but not multivariable (p=0.198) models. Among brain tumor patients receiving RT, increased depression and anxiety symptoms independently predicted for worsening neurocognitive function, particularly in attention and processing speed. Evaluating and treating symptoms of depression and anxiety may optimize neurocognitive functioning in these patients.