Cognitive issues in patients with IDH mutant gliomas: from neuroscience to clinical neuropsychology.

PURPOSE: The understanding of cognitive symptoms in patients with IDH-Mutant gliomas (IDH-Mut) is rapidly developing. In this article, we summarize the neuroscientific knowledge base regarding the influence of IDH-Mut tumors and their treatment on cognition and provide guidance regarding the management of these symptoms in patients. METHODS: We performed a review of peer reviewed publications relevant to IDH-Mut glioma and cognitive outcomes and provide an overview of the literature as well as a case example to clarify management strategies. RESULTS: At the time of presentation, patients with IDH-Mut gliomas have a favorable cognitive profile as compared with those with IDH-wild type (WT) tumors. The relatively low cognitive burden may reflect the slower growth rate of IDH-Mut tumors, which is less disruptive to both local and widespread neural networks. Human connectomic research using a variety of modalities has demonstrated relatively preserved network efficiency in patients with IDH-Mut gliomas as compared with IDH-WT tumors. Risk of cognitive decline from surgery can potentially be mitigated by careful integration of intra-operative mapping. Longer term cognitive risks of tumor treatment, including chemotherapy and radiation, are best managed by instituting neuropsychological assessment as part of the long-term care of patients with IDH-Mutant glioma. A specific timeline for such integrative care is provided. CONCLUSIONS: Given the relative recency of the IDH-mutation based classification of gliomas, as well as the long time course of this disease, a thoughtful and comprehensive strategy to studying patient outcomes and devising methods of cognitive risk reduction is required.

Assessment and Management of Cognitive Symptoms in Patients With Brain Tumors.

Cognitive symptoms occur in almost all patients with brain tumors at varying points in the disease course. Deficits in neurocognitive function may be caused by the tumor itself, treatment (surgery, radiation, or chemotherapy), or other complicating factors (e.g., seizures, fatigue, mood disturbance) and can have a profound effect on functional independence and quality of life. Assessment of neurocognitive function is an important part of comprehensive care of patients with brain tumors. In the neuro-oncology clinic, assessment may include cognitive screening tools and inquiry into subjective cognitive function. Neuropsychological assessment is an important adjunct to identify cognitive symptoms and can be used as an opportunity to intervene through transformative feedback and treatment planning. Preventative measures can be taken to reduce cognitive side effects of treatment, such as awake craniotomies with intraoperative mapping during neurosurgery or prophylactic measures during radiation therapy (e.g., hippocampal avoidance, neuroprotectant treatment with memantine). Rehabilitative therapies, including cognitive rehabilitation and computerized cognitive exercise, are options for managing cognitive problems in an individualized manner. Pharmacotherapy, including use of stimulant medications and acetylcholinesterase inhibitors, has shown benefits for patients with brain tumors when tailored to an individual's cognitive profile. Identification and management of co-occurring issues, such as sleep disturbance, fatigue, and depression, can also improve neurocognitive function. There are promising therapies under development that may provide new options for treatment in the future. Integrating careful assessment and treatment of cognition throughout the disease course for patients with brain tumors can improve functional outcomes and quality of life.

Anterior medial temporal lobe activation during encoding of words: FMRI methods to optimize sensitivity.

The existence of a rostrocaudal gradient of medial temporal lobe (MTL) activation during memory encoding has historically received support from positron emission tomography studies, but less so from functional MRI (FMRI) studies. More recently, FMRI studies have demonstrated that characteristics of the stimuli can affect the location of activation seen in the MTL when those stimuli are encoded. The current study tested the hypothesis that MTL activation during memory encoding is related to the modality of stimulus presentation. Subjects encoded auditorily or visually presented words in an FMRI novelty paradigm. Imaging and analysis parameters were optimized to minimize susceptibility artifact in the anterior MTL. Greater activation was observed in the anterior than posterior MTL for both modalities of stimulus presentation. The results indicate that anterior MTL activation occurred during encoding, independent of stimulus modality and provide support for the hypothesis that verbal-semantic memory processing occurs in anterior MTL. The authors suggest that technical factors are critical for observing the rostrocaudal gradient in MTL memory activation.