Kyle R. Noll

Clinical Characteristics, Pathophysiology, and Management of Noncentral Nervous System Cancer-Related Cognitive Impairment in Adults

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Neurocognitive Changes Associated With Surgical Resection of Left and Right Temporal Lobe Glioma.

BACKGROUND Little is known regarding the neurocognitive impact of temporal lobe tumor resection. OBJECTIVE To clarify subacute surgery-related changes in neurocognitive functioning (NCF) in patients with left (LTL) and right (RTL) temporal lobe glioma. METHODS Patients with glioma in the LTL (n = 45) or RTL (n = 19) completed comprehensive pre- and postsurgical neuropsychological assessments. NCF was analyzed with 2-way mixed design repeated-measures analysis of variance, with hemisphere (LTL or RTL) as an independent between-subjects factor and pre- and postoperative NCF as a within-subjects factor. RESULTS About 60% of patients with LTL glioma and 40% with RTL lesions exhibited significant worsening on at least 1 NCF test. Domains most commonly impacted included verbal memory and executive functioning. Patients with LTL tumor showed greater decline than patients with RTL tumor on verbal memory and confrontation naming tests. Nonetheless, over one-third of patients with RTL lesions also showed verbal memory decline. CONCLUSION In patients with temporal lobe glioma, NCF decline in the subacute postoperative period is common. As expected, patients with LTL tumor show more frequent and severe decline than patients with RTL tumor, particularly on verbally mediated measures. However, a considerable proportion of patients with RTL tumor also exhibit decline across various domains, even those typically associated with left hemisphere structures, such as verbal memory. While patients with RTL lesions may show even greater decline in visuospatial memory, this domain was not assessed. Nonetheless, neuropsychological assessment can identify acquired deficits and help facilitate early intervention in patients with temporal lobe glioma.

The effect of IDH1 mutation on the structural connectome in malignant astrocytoma

Mutation of the IDH1 gene is associated with differences in malignant astrocytoma growth characteristics that impact phenotypic severity, including cognitive impairment. We previously demonstrated greater cognitive impairment in patients with IDH1 wild type tumor compared to those with IDH1 mutant, and therefore we hypothesized that brain network organization would be lower in patients with wild type tumors. Volumetric, T1-weighted MRI scans were obtained retrospectively from 35 patients with IDH1 mutant and 32 patients with wild type malignant astrocytoma (mean age = 45 ± 14 years) and used to extract individual level, gray matter connectomes. Graph theoretical analysis was then applied to measure efficiency and other connectome properties for each patient. Cognitive performance was categorized as impaired or not and random forest classification was used to explore factors associated with cognitive impairment. Patients with wild type tumor demonstrated significantly lower network efficiency in several medial frontal, posterior parietal and subcortical regions (p < 0.05, corrected for multiple comparisons). Patients with wild type tumor also demonstrated significantly higher incidence of cognitive impairment (p = 0.03). Random forest analysis indicated that network efficiency was inversely, though nonlinearly associated with cognitive impairment in both groups (p < 0.0001). Cognitive reserve appeared to mediate this relationship in patients with mutant tumor suggesting greater neuroplasticity and/or benefit from neuroprotective factors. Tumor volume was the greatest contributor to cognitive impairment in patients with wild type tumor, supporting our hypothesis that greater lesion momentum between grades may cause more disconnection of core neurocircuitry and consequently lower efficiency of information processing.

Commentary: “Neuropsychological Assessment of Individuals with Brain Tumor: Comparison of Approaches Used in the Classification of Impairment”

Approaches to classifying neuropsychological impairment after brain tumor vary according to testing level (individual tests, domains or global index) and source of reference (i.e., norms, controls and premorbid functioning). This study aimed to compare rates of impairment according to different classification approaches. Participants were 44 individuals (57% female) with a primary brain tumor diagnosis (mean age = 45.6 years) and 44 matched control participants (59% female, mean age = 44.5 years). All participants completed a test battery that assesses premorbid IQ (Wechsler Adult Reading Test), attention/processing speed (Digit Span, Trail Making Test A), memory (Hopkins Verbal Learning Test – Revised, Rey-Osterrieth Complex Figure-recall) and executive function (Trail Making Test B, Rey-Osterrieth Complex Figure copy, Controlled Oral Word Association Test). Results indicated that across the different sources of reference, 86-93% of participants were classified as impaired at a test-specific level, 61-73% were classified as impaired at a domain-specific level, and 32-50% were classified as impaired at a global level. Rates of impairment did not significantly differ according to source of reference (p>.05); however, at the individual participant level, classification based on estimated premorbid IQ was often inconsistent with classification based on the norms or controls. Participants with brain tumor performed significantly poorer than matched controls on tests of neuropsychological functioning, including executive function (p=.001) and memory (p.05). These results highlight the need to examine individuals’ performance across a multi-faceted neuropsychological test battery to avoid over- or under-estimation of impairment.

Relationships between neurocognitive functioning, mood, and quality of life in patients with temporal lobe glioma

While neurocognitive functioning (NCF) and mood disturbance share a relationship with health‐related quality of life (HRQOL), few studies have examined relationships between these constructs in glioma patients prior to treatment.

Neurocognitive functioning and genetic variation in patients with primary brain tumours.

Impairment of neurocognitive functioning is a common result of cerebral neoplasms and treatment, although there is substantial heterogeneity in the pattern and severity of neurocognitive dysfunction across individuals and tumour types. The effects of many clinical and patient characteristics on neurocognitive functioning have been documented, but little research has been devoted to understanding the effect of genetic variation on neurocognitive outcomes in patients with brain tumours. This Review highlights preliminary evidence that suggests an association between various genes and risk of adverse neurocognitive outcomes in patients with brain tumours. Studies include genes specific to neuronal function, and those associated with more systemic cellular regulation. Related scientific literature in other disease populations is briefly discussed to indicate additional candidate genes. We consider methodological issues central to the study of neurocognitive functioning and genetic associations for patients with brain tumours, and emphasise the need for future research integrating novel investigative techniques.

Verbal Learning Processes in Patients with Glioma of the Left and Right Temporal Lobes

Recent research supports the utility of process variables in understanding mechanisms underlying memory impairments. The Hopkins Verbal Learning Test-Revised (HVLT-R) was administered to 84 patients with left (LTL, n = 58) or right temporal lobe glioma (RTL, n = 26) prior to surgical resection. Primary HVLT-R measures of learning and memory and numerous learning process indices were computed. Both groups exhibited frequent memory impairment (>30%), with greater severity in the LTL group. Patients with LTL glioma also exhibited lower semantic clustering scores than RTL patients, which were highly associated with Total Recall (ρ = 0.83) and Delayed Recall (ρ = 0.68). Learning slope and a novel measure of learning efficiency were also significantly associated with primary memory measures, though scores were similar across the LTL and RTL groups. While lesions to either temporal lobe impact verbal memory, semantic encoding appears to depend upon the integrity of LTL structures in particular.

Neurocognitive functioning is associated with functional independence in newly diagnosed patients with temporal lobe glioma

Background Cancer and treatment-related neurocognitive dysfunction has the potential to significantly disrupt the lives of survivors. While neurocognitive functioning is known to predict aspects of patient-reported quality of life in individuals with glioma, little is known regarding the association between neurocognitive functioning and clinician-rated functional independence. Methods Newly diagnosed patients with glioma in the left (n = 73; 49% glioblastoma) or right (n = 30; 57% glioblastoma) temporal lobe completed comprehensive neuropsychological testing. Clinicians rated patient functional independence using the Functional Independence Measure (FIM) and Karnofsky Performance Status (KPS) scale. Correlational and regression analyses were conducted to determine relationships between neurocognitive functioning and functional independence. Results Tests of verbal learning, executive function, and language comprehension were moderately to strongly associated with clinician-rated functional independence, particularly for items pertaining to need for assistance with memory, problem-solving, and language functions. Stepwise linear regression showed that tests of verbal learning, executive functioning, and language comprehension predicted FIM ratings, together accounting for 40% of variance (P < .001). A test of executive functioning also predicted KPS scores and accounted for 19% of variance (P < .001). Conclusions In patients with newly diagnosed temporal lobe glioma, neurocognitive functioning is associated with functional independence. Verbal learning, executive functioning, and language comprehension demonstrated the strongest associations across both measures of functional independence. These findings provide support for the ecological validity of neuropsychological assessment by demonstrating the real-world clinical significance of objectively assessed neurocognitive functioning in glioma patients.

IClinfMRI software for integrating functional MRI techniques in presurgical mapping and clinical studies

Task-evoked and resting-state (rs) functional magnetic resonance imaging (fMRI) techniques have been applied to the clinical management of neurological diseases, exemplified by presurgical localization of eloquent cortex, to assist neurosurgeons in maximizing resection while preserving brain functions. In addition, recent studies have recommended incorporating cerebrovascular reactivity (CVR) imaging into clinical fMRI to evaluate the risk of lesion-induced neurovascular uncoupling (NVU). Although each of these imaging techniques possesses its own advantage for presurgical mapping, a specialized clinical software that integrates the three complementary techniques and promptly outputs the analyzed results to radiology and surgical navigation systems in a clinical format is still lacking. We developed the Integrated fMRI for Clinical Research (IClinfMRI) software to facilitate these needs. Beyond the independent processing of task-fMRI, rs-fMRI, and CVR mapping, IClinfMRI encompasses three unique functions: (1) supporting the interactive rs-fMRI mapping while visualizing task-fMRI results (or results from published meta-analysis) as a guidance map, (2) indicating/visualizing the NVU potential on analyzed fMRI maps, and (3) exporting these advanced mapping results in a Digital Imaging and Communications in Medicine (DICOM) format that are ready to export to a picture archiving and communication system (PACS) and a surgical navigation system. In summary, IClinfMRI has the merits of efficiently translating and integrating state-of-the-art imaging techniques for presurgical functional mapping and clinical fMRI studies.

Neuropsychological Practice in the Oncology Setting

Oncology has experienced positive shifts in survival curves for many cancers largely due to the development of earlier diagnostics and better therapeutics. This has increased the visibility and need for survivorship services, including clinical neuropsychology. Patients with cancer frequently experience cognitive dysfunction related to the presence of cancer itself and treatment neurotoxicity. These cognitive difficulties can profoundly impact patient functioning and autonomy with accompanying declines in quality of life. Clinical neuropsychologists are uniquely positioned to evaluate the cognitive and affective sequelae of cancer and treatment and provide interventions and recommendations that can benefit well-being and potentially alter the disease course. Despite increasing recognition of the importance of neuropsychological issues to cancer survivorship, many neuropsychologists have limited training and guidance regarding navigating and implementing services within the oncology setting. This article provides the basic rationale for neuropsychological practice and research activities in oncology, as well as the experience of the Section of Neuropsychology at The University of Texas MD Anderson Cancer Center.