Review: Cognitive Issues in Patients With IDH-mutant Gliomas

IDH-mutant gliomas are now known to be less disruptive to neurocognitive function than IDH–wild type tumors. Still, patients with IDH-mutant disease, who are generally in young adulthood, commonly experience cognitive symptoms that can interfere with their education, careers, and family lives. The long survival times associated with these tumors mean that individuals are at risk for development of long term cognitive consequences of their disease and treatment.

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In the Journal of Neuro-Oncology, Michael W. Parsons, PhD, a neuropsychologist in the Pappas Center for Neuro-Oncology and Department of Psychiatry at Massachusetts General Hospital, in collaboration with David S. Sabsevitz, PhD, of Mayo Clinic Jacksonville, review the evidence about cognitive care for patients with IDH-mutant glioma and make suggestions based on their long clinical experience.

Overview of Neuropsychological Assessment

Brief screening tools such as the Mini–Mental State Examination aren't sensitive enough to detect the subtle changes in cognition that are common in IDH-mutant glioma. Instead, patients should have neuropsychological (NP) assessments to monitor objective cognitive changes, which can identify tumor progression sooner than brain imaging.

To assess subjective symptoms, clinicians frequently use a quality-of-life scale, such as the Functional Assessment for Cancer Therapy–Brain or the European Organization for Research and Treatment of Cancer QLQ-C30.

Preoperative Assessment

Preoperative NP assessment has a number of advantages:

• Helps identify relevant domains for intraoperative mapping (IOM)
• Familiarizes the patient with the protocols they may be exposed to during surgery
• Allows selection of items each patient can respond to reliably and accurately, improving confidence that errors during surgery represent true surgical effects or disruption from stimulation
• Detect problems that might interfere with IOM (e.g., anxiety, aphasia or inadequate attention)
• Recognize neurocognitive patterns critical for interpreting functional MRI and IOM (e.g., non-dominant hemisphere language representation and optimization of functional outcome)
• Predict risk of cognitive decline as a complication of surgery

The assessments should be brief but sample all relevant cognitive domains as informed by the functional anatomy of the tumor and planned surgery. Typical choices are:

• Visuospatial/perceptual tasks, such as perceiving line orientation, simple drawings, and more complex figure drawings
• Screening of multiple aspects of language with repeatable measures such as the Quick Aphasia Battery and Controlled Oral Word Association Test
• Tasks from the Wechsler Adult Intelligence Scales, such as the Coding and/or Digit Span tasks, to assess information processing speed and working memory
• The Trail Making Test or a Stroop paradigm to evaluate executive function
• Measures of learning and recall of both verbal and visuospatial material (e.g., the Hopkins Verbal Learning Test–Revised and the Brief Visuospatial Memory Test–Revised)

Intraoperative Mapping

The cognitive tasks used during IOM should be highly individualized based on the functional neuroanatomy of the brain regions at risk, proximity of the tumor to known eloquent areas, preoperative mapping from functional neuroimaging, presenting symptoms and baseline NP performance.

Testing during IOM should include the most relevant cognitive domains for the individual, based on symptoms of the patient and understanding of the neural networks at risk during surgery. Intraoperative cognitive monitoring—continuous testing and assessment of cognitive changes and evolving deficits—can be used during active resection to further reduce cognitive morbidity.

Postoperative Assessment

After tumor resection, a brief NP evaluation is useful to characterize acute and subacute deficits that may benefit from treatment. It generally includes repeatable and alternate forms of the measures administered preoperatively.

A more comprehensive evaluation is indicated once the patient recovers from acute side effects of surgery and immediate postsurgical treatments. Besides the measures administered preoperatively, it can include a battery of tests to assess higher-level functions and evaluate for subtle issues that affect decisions about return to work or the need for longer-term rehabilitation.

Regular follow-up NP assessment (e.g., one year after surgery and periodically thereafter as needed) is recommended to identify cognitive changes caused by tumor recurrence/progression, effects of treatment and neurologic or medical complications.

Neurocognitive Intervention

Treatments for cognitive deficits in patients with IDH-mutant glioma can include:

• Compensatory strategies
• Environmental modification
• Cognitive rehabilitation (supported by research in heterogeneous brain tumor types, not glioma specifically)
• Computerized cognitive strategy training or cognitive stimulation

The utility of cognitive-enhancing medications is also being explored for patients with brain tumors.

The article includes a case study that illustrates many of these points.

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