Longitudinal Analysis of Depression and Anxiety Symptoms as Independent Predictors of Neurocognitive Function in Primary Brain Tumor Patients

Abstract

Purpose: Primary brain tumor patients are vulnerable to depression and anxiety symptoms, which may affect their neurocognitive functioning. We performed a prospective longitudinal analysis to examine the association between depression and anxiety symptoms and domain-specific neurocognitive functioning in primary brain tumor patients receiving radiation therapy (RT).

Methods and materials: On a prospective trial, 54 primary brain tumor patients receiving RT underwent comprehensive neurocognitive evaluation at baseline (pre-RT), and 3, 6, and 12 months post-RT. Neurocognitive assessments measured attention/processing speed, verbal and visuospatial memory, and executive functioning, including Delis-Kaplan Executive Function System Trail-Making Test (DKEFS-TMT), DKEFS Verbal Fluency, and Brief Visuospatial Memory Test-Revised. Depression and anxiety symptoms were also assessed at each time point with Beck Depression and Anxiety Inventories (BDI-II and BAI), respectively. Higher scores reflect more numerous or severe depression or anxiety symptoms. Univariable and multivariable linear mixed-effects models assessed associations between BDI-II and BAI scores and domain-specific neurocognitive scores over time, controlling for pre-existing depression or anxiety disorders and other patient, tumor, and treatment characteristics.

Results: Higher BAI scores were associated with worse attention and processing speed in univariable analyses: DKEFS-TMT visual scanning (P = .003), number sequencing (P = .011), and letter sequencing (P <.001). On multivariable analyses, these associations remained significant (all P ≤ .01). Higher BDI-II scores were also associated with poorer attention/processing speed (DKEFS-TMT Letter Sequencing) in univariable (P = .002) and multivariable (P = .013) models. Higher BAI scores were associated with worse visuospatial memory (Brief Visuospatial Memory Test-Revised Delayed Recall) on univariable (P = .012) but not multivariable analyses (P = .383). Similarly, higher BDI-II scores were associated with poorer executive functioning (DKEFS Verbal Fluency Category Switching) on univariable (P = .031) but not multivariable analyses (P = .198).

Conclusions: Among primary brain tumor patients receiving RT, increased depression and anxiety were independently associated with worsened neurocognition, particularly in attention/processing speed. Depression and anxiety symptoms should be controlled for in prospective clinical trials and managed in the clinical setting to optimize neurocognitive functioning.

Fig. 1.

BDI and BAI scores over time. Boxplots and line plots for raw BDI and BAI scores over time. Line plots are mean scores over time with error bars representing the 95% confidence intervals. (a and b) BDI scores are not statistically different over time. (c and d) BAI scores significantly decrease over time (P = .003).

Fig. 2.

(a) Univariable linear mixed effects regression of anxiety symptoms on cognitive function. (b) Multivariable linear mixed effects regression of anxiety symptoms on cognitive function. Linear mixed effects analyses of BAI as a predictor of neurocognitive function. Assessments of attention or processing (5), executive functioning (3), and memory (4) are shown. Each assessment investigated with a unique model. β estimates are shown by dot. Whiskers reflect 95% confidence interval of the estimate. Significant associations are reflected by 95% confidence interval that do not cross the 0.0 reference line. (a) Shows univariable models. (b) Shows multivariable models, controlled for appropriate covariates. Abbreviations: BVMT-R Brief Visuospatial Memory Test-Revised; CI = confidence interval; DKEFS-TMT = Delis-Kaplan Executive Function System Trail-Making Test; DKEFS-VF = DKEFS Verbal Fluency; HVLT = Hopkins Verbal Learning Test-Revised; WCST = Wisconsin Card Sort Test.

Fig. 3.

(a) Univariable linear mixed effects regression of depression symptoms on cognitive function. (b) Multivariable linear mixed effects regression of depression symptoms on cognitive function. Linear mixed effects analyses of BDI as a predictor of neurocognitive function assessments of attention and processing (5), executive functioning (3), and memory (4) are shown. Each assessment investigated with a unique model. β estimates are shown by dot. Whiskers reflect 95% confidence interval of the estimate. Significant associations are reflected by 95% confidence interval that do not cross the 0.0 reference line. (a) Shows univariable models. (b) Shows multivariable models, controlled for appropriate covariates. Abbreviations: BVMT-R Brief Visuospatial Memory Test-Revised; CI = confidence interval; DKEFS-TMT = Delis-Kaplan Executive Function System Trail-Making Test; DKEFS-VF = DKEFS Verbal Fluency; HVLT = Hopkins Verbal Learning Test-Revised; WCST = Wisconsin Card Sort Test.