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

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.