Neurocognitive testing holds significant potential in predicting complications in patients with non-Hodgkin’s lymphoma (NHL), particularly neurological and cognitive impairments that may arise due to the disease itself or its treatment. NHL, a diverse group of blood cancers affecting lymphocytes, can lead to various neurophysiological dysfunctions either directly through tumor effects or indirectly via treatment-related toxicity, systemic inflammation, or paraneoplastic syndromes. Neurocognitive testing, which assesses functions such as memory, attention, executive function, and processing speed, can serve as an important tool to detect early signs of neurological complications and guide clinical management.
Non-Hodgkin’s lymphoma patients are at risk for a range of neurological complications. These include cognitive dysfunction often referred to as “chemo brain,” peripheral neuropathy, encephalopathy, seizures, and chronic neuropathic pain. These complications can arise from multiple mechanisms: direct tumor invasion or compression of neural structures, immune-mediated paraneoplastic neurological syndromes, systemic inflammation disrupting the blood-brain barrier, and neurotoxic effects of chemotherapy, radiotherapy, or immunotherapy. Cognitive impairment is among the most common and distressing complications, significantly affecting quality of life and treatment adherence.
Neurocognitive testing can detect subtle changes in brain function that may precede overt clinical symptoms. For example, standardized tests measuring attention, memory, and executive function can reveal deficits caused by chemotherapy-induced neurotoxicity or metabolic disturbances such as vitamin deficiencies or electrolyte imbalances. Early identification of these impairments allows for timely interventions, such as modifying treatment regimens, initiating cognitive rehabilitation, or addressing reversible metabolic causes, potentially preventing irreversible neurological damage.
The complexity of neurological complications in NHL patients stems from the interplay of cancer biology, treatment effects, and patient-specific factors. Paraneoplastic neurological syndromes, caused by immune cross-reactivity between tumor antigens and neural tissue, can lead to rapid and severe neurological decline. Neurocognitive testing, combined with emerging diagnostic tools like functional MRI, EEG, and cerebrospinal fluid biomarkers, enhances the ability to detect these syndromes early. Additionally, systemic inflammation and metabolic dysregulation common in cancer patients can exacerbate neuroinflammation and neuronal injury, further underscoring the need for comprehensive neurocognitive assessment.
Treatment-related neurotoxicity is a major contributor to long-term cognitive sequelae in NHL patients. Chemotherapy agents, especially those crossing the blood-brain barrier, can cause direct neuronal damage or disrupt neural networks. Radiotherapy targeting the central nervous system can also impair cognitive functions. Neurocognitive testing before, during, and after treatment helps monitor the trajectory of cognitive changes, enabling clinicians to balance effective cancer control with preservation of neurological function.
In pediatric and young adult NHL patients, neurocognitive testing is particularly crucial. Survivors of childhood cancers, including lymphomas, often face chronic health conditions and cognitive deficits as late effects of therapy. These deficits can impact educational attainment, social integration, and overall quality of life. Early neuropsychological assessment facilitates identification of at-risk individuals and implementation of supportive educational and therapeutic interventions.
Advances in technology and machine learning are enhancing the predictive power of neurocognitive testing. By integrating cognitive test results with clinical, imaging, and biomarker data, predictive models can be developed to identify patients at highest risk for neurological complications. This personalized approach allows for tailored monitoring and intervention strategies.
Despite its promise, neurocognitive testing in NHL patients faces challenges. Variability in testing methods, timing, and interpretation can affect reliability. Cognitive impairments may be subtle or fluctuate, requiring repeated assessments. Moreover, differentiating between disease-related, treatment-related, and psychosocial contributors to cognitive dysfunction demands a multidisciplinary approach.
In clinical practice, neurocognitive testing should be part of a comprehensive evaluation for NHL patients, especially those undergoing intensive chemotherapy or CNS-directed therapies. Routine metabolic screening is also important t
