Cognitive disability in adult patients with brain tumors

doi:10.1016/j.ctrv.2018.02.007

Cancer Treatment Reviews

Volume 65, April 2018, Pages 33-40

https://doi.org/10.1016/j.ctrv.2018.02.007 Get rights and content

Highlights

•
Cognitive dysfunction represents a significant problem in the lives of brain tumor patients.
•
The impact of cognitive dysfunction on patients’ QoL needs to be given serious consideration and should not be ignored.
•
Focus on improving quality of life of patients with brain tumors is paramount to patient centered care.
•
A multidisciplinary approach to the management of brain tumors is beneficial in devising adequate treatment plans and minimizing adverse events.

Abstract

Cognitive dysfunction is common among patients with intracranial tumors. Most cognitive deficits are subtle, lack specificity, may mimic depression or other neurological disorders and may be recognized in retrospect by the physician. In certain cases, distinguishing between tumor recurrence and cognitive deficits that arise as a consequence of the treatment becomes challenging. Late treatment effects have also become an area of focus as the overall survival and prognosis of patients with brain tumors increases. New data has highlighted the importance of less toxic adjuvant therapies owing to their positive impact on prognosis and quality of life. Various experimental therapies and genetic influences on individual sensitivity towards injury are promising steps towards a better management strategy for cognitive dysfunction. In this literature review, we discuss cognitive dysfunction as a manifestation of intracranial tumors, treatment modalities such as radiotherapy, chemotherapy, surgery and their impact on cognition and patients' quality of life. We also discuss management options for cognitive dysfunction and emerging therapies.

Introduction

Cognitive dysfunction can be defined as impairment in one or more cerebral functions such as language, attention, memory and executive function. These functions can become altered due to both cortical and subcortical lesions. Cognitive dysfunction in brain tumors can be a manifestation of the tumor itself, the treatment modalities used, or a combination of both. Since one third of primary brain tumors are considered malignant and as aggressive and advanced treatment strategies showing better outcomes gain ground, focus on late effects of treatment and their impact on patient well-being is becoming of significant importance. Cognitive deficits have been shown to have a negative impact on patients’ health related quality of life (HRQoL) [1]. Quality of life (QoL) is now as important a measure as other traditional outcome measures such as overall survival (OS) and progression-free survival (PFS) [2], with HQRoL being an independent prognostic factor in both primary and metastatic brain tumors [3]. In this review, we discuss etiology, current testing strategies and effects of cognitive dysfunction as well as current and emerging strategies. A multidisciplinary approach for the management of brain tumor patients is proposed.

Section snippets

Cognitive testing

Neuropsychological (NP) testing to assess cognitive dysfunction is crucial as the data that is collected from NP assessment can be used to monitor disease progression, guide future therapies, and rehabilitation measures that aim to improve a patient’s quality of life [4]. Cognitive testing can be carried out as part of a multi-faceted evaluation similar to the evaluation of performance status, which contains elements of both cognitive and motor function. It could also be done by a test or a set

Tumor as a cause of cognitive dysfunction

Patients with brain tumors often present with cognitive complaints and deficits. Seizures and cognitive disorders are the two dominant presenting symptoms in glioma patients [15]. The nature of cognitive impairment is dependent on several factors including tumor grade, location, and size. Temporal lobe gliomas usually present with impairment in the domains of verbal learning, memory, and language [16]. Frontal lobe lesions, on the other hand, can present with behavioral and emotional changes

Radiotherapy as a cause of cognitive dysfunction

Radiation-induced cognitive impairment has been reported to occur in 27–90% of adult patients with brain tumors [4], [25]. It is usually divided into acute effects, occurring during radiation and up to six weeks afterwards, early delayed effects that can occur up to six months after radiotherapy (RT), and late effects that can develop six months or more after RT. Unlike early effects, late effects are often irreversible. The effects of RT on the brain have been radiographically demonstrated

Chemotherapy induced cognitive dysfunction

The neurotoxic side effects of chemotherapy may be difficult to differentiate from RT, as patients treated with chemotherapy may have been previously treated with RT or are being treated concomitantly. Most studies done to assess chemotherapy induced cognitive dysfunction have been performed in patients with breast cancer. The literature contains reports noting chemotherapy-induced cognitive dysfunction (CICD) 2–10 years post chemotherapy [43], [44]. Deficits can range from subtle changes that

Role of surgery in cognitive dysfunction

Since the management of CNS tumors frequently involves a combination of surgery and radio-chemotherapy, separating the effects of the various treatments is often not feasible [28]. Recently, mutations in the enzyme isocitrate dehydrogenase 1 (IDH1-M) gene have shown to exhibit a survival benefit over the IDH1 wild type gene (IDH1-WT), due to the fact that tumors with IDH1-WT are more proliferative and aggressive than IDH1-M tumors (have greater tumor momentum) [55]. This translates to a worse

Pharmacotherapy

Various Pharmacological agents are being researched to be used in the management of cognitive dysfunction. Table 2 includes some of the relevant agents.

Role of rehabilitation programs in the management of cognitive dysfunction

As part of a multidisciplinary approach, patients with brain tumors can benefit from early evaluation by a rehabilitation physician. A rehabilitation plan can include assessment and management of cognitive and physical impairments with training and reinforcement. Patients are encouraged to participate in an active lifestyle with individual

Conclusion

Cognitive dysfunction represents a significant problem in the lives of brain tumor patients. The impact of cognitive dysfunction on patients’ QoL needs to be given serious consideration and should not be ignored. A multidisciplinary team approach involving medical and non-medical personnel should be part of the routine care of all brain tumor patients. Physician family interactions and tumor support groups are crucial and should be incorporated early. Risk factors that predispose to cognitive

Financial support/grants

None.

Conflict of interest

None.

Disclosure statement

Authors have nothing to disclose.

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Understanding experiences of cognitive decline and cognitive assessment from the perspectives of people with glioma and their caregivers: A qualitative interview study
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Despite the impact of cognitive decline during brain cancer care, implementing routine cognitive assessment can be challenging. Effective implementation of cognitive assessment necessitates an understanding of implementation from the patient perspective. However, little is known about how people with glioma and their caregivers experience cognitive changes, assessment and support.
To understand the lived experiences of changes in cognition for people with glioma and their caregivers including experiences of: i) perceived or objectively measured cognitive decline (or absence of decline); ii) cognitive assessment following diagnosis, and; iii) met and unmet cognition-related supportive care needs.
Semi-structured qualitative telephone interviews were conducted with people with gliomas and support persons and analysed using reflexive thematic analysis.
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Semi-structured qualitative telephone interviews were conducted with people with gliomas and caregivers and analysed using reflexive thematic analysis.
People with glioma (n = 5) and caregivers (n = 13) completed interviews. Four themes were identified: Cognition needs to be considered within the context of glioma diagnosis and treatment; concerns about cognition were initially subordinate to survival but become important; there are challenges identifying and communicating about people with gliomas’ changes in cognition; cognition-related supportive care can be helpful but challenging for people with glioma and caregivers to identify and access.
Changes to cognition can have considerable impacts of people with glioma and their caregivers which may be overshadowed by treatment and survival. A multi-disciplinary approach to timely cognitive screening, structured referral pathways, and communication with caregivers may provide opportunities for support.
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Citation Excerpt :
Beyond the expected psychological distress of a cancer diagnosis,14 brain tumors are unique in that they may contribute to direct focal cerebral dysfunction and induce inherent neurodegenerative processes.15 In addition to the neurophysiologic effects of brain tumor invasion on the surrounding native tissue, adjuvant chemotherapy and radiotherapy can also induce cerebral edema and necrosis in peritumoral tissue or accelerate vascular dementia.16 These neuropsychiatric effects can further contribute to the development of depression in patients with malignant brain tumor.
Quality of life is paramount in patients with advanced cancer and may be adversely affected by comorbid depression. We hypothesized that comorbid depression is associated with higher rates of postoperative complications, worse functional outcomes, and higher rates of readmission after craniotomy for resection of malignant intracranial tumors.
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Of the 57,621 craniotomies for malignant neoplasms included in the analysis, 11.32% of patients had clinically diagnosed MDD. The presence of MDD was associated with nonroutine discharge (odds ratio, 1.10–125; P < 0.0001) as well as higher rates of neurologic complications (odds ratio, 1.03–1.18; P = 0.003). No association between MDD and 30-day or 90-day readmissions was noted. Patients with major All Patient Refined Diagnosis Related Groups severity and index length of stay >7 days experienced higher rates of 30-day and 90-day readmissions.
There is a clinically significant rate of comorbid MDD in patients with malignant intracranial tumors, and MDD is associated with worse perioperative outcomes. Given the wealth of behavioral and pharmaceutical therapies available, MDD is a modifiable risk factor in this cohort that clinicians should be vigilant in screening for and initiating appropriate treatment protocols.
Cognitive impairment following radiation to hippocampus and other brain structures in adults with primary brain tumours
2020, Radiotherapy and Oncology
Radiation therapy (RT) to the brain may result in cognitive impairment. The primary objective of the present study was to examine the relationship between RT dose to the hippocampus and learning and memory functions. Secondary objective was to examine relationships between doses to other brain structures and specific cognitive functions.
A cross-sectional analysis was undertaken in 78 primary brain tumour patients after RT. Cognitive function was assessed by neuropsychological tests. Test scores were standardized using normative data adjusted for age and level of education. Test-specific cognitive impairment was determined as a z-score ≤−1.5. Radiation dose to brain structures and test-specific cognitive impairment outcomes were fitted to a logistic regression model.
High RT dose to the left hippocampus was associated with impaired verbal learning and memory (p = 0.04). RT dose to the left hippocampus, left temporal lobe, left frontal lobe and total frontal lobe were associated with verbal fluency impairment (p < 0.05) and doses to the thalamus and the left frontal lobe with impaired executive functioning (p ≤ 0.03). Finally, RT dose to the brain and thalamus were associated with impaired processing speed (p ≤ 0.05).
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Complications of TreatmentCognitive disability in adult patients with brain tumors

Highlights

Abstract

Introduction

Section snippets

Cognitive testing

Tumor as a cause of cognitive dysfunction

Radiotherapy as a cause of cognitive dysfunction

Chemotherapy induced cognitive dysfunction

Role of surgery in cognitive dysfunction

Pharmacotherapy

Role of rehabilitation programs in the management of cognitive dysfunction

Conclusion

Financial support/grants

Conflict of interest

Disclosure statement

Lancet Oncol

J Psychiatr Res

Surg Neurol

Int J Radiat Oncol

Clin Neurol Neurosurg

Lancet Neurol

Cancer Lett

Lancet Oncol

Clin Oncol

Crit Rev Oncol Hematol

Neurosci Biobehav Rev

Clin Neurophysiol

Int J Radiat Oncol

Int J Radiat Oncol

Int J Radiat Oncol

J Clin Neurosci

J Physiother

Complement Ther Clin Pract

Lancet Oncol

Effect of neurological dysfunction on health-related quality of life in patients with high-grade glioma

J Neurooncol

Evaluating health-related quality of life and symptom burden in brain tumour patients: instruments for use in experimental trials and clinical practice

Curr Opin Neurol

Cognitive function as a predictor of survival in patients with recurrent malignant glioma

J Clin Oncol

Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors

J Clin Oncol

Measuring clinical outcomes in neuro-oncology. A battery to evaluate low-grade gliomas (LGG)

J Neurooncol

Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study

Cancer

A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer

Br J Cancer

Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen

J Clin Exp Neuropsychol

Neuropsychological dysfunction associated with cancer and cancer therapies: a conceptual review of an emerging target

Br J Cancer

Neuropsychological assessment

Presenting symptoms of glioma in adults

Acta Neurol Scand

Mental symptoms in cases of tumor of temporal lobe

Am J Psychiatry

Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions

Brain

Evidence for a dysfunctional prefrontal circuit in patients with an impulsive aggressive disorder

Proc Natl Acad Sci

The mental symptoms associated with 58 cases of cerebral tumour

J Neurol Psychopathol

Brain tumors

N Engl J Med

Investigation of cognitive impairments in people with brain tumors

J Neurooncol

The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study

Effect of focal and nonfocal cerebral lesions on functional connectivity studied with MR imaging

AJNR Am J Neuroradiol

Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy

J Clin Oncol

Radiation injury of the brain

AJNR Am J Neuroradiol

Neurologic, neuropsychologic, and computed cranial tomography scan abnormalities in 2- to 10-year survivors of small-cell lung cancer

J Clin Oncol

Medical effects of ionizing radiation

Radiation injury to the central nervous system

Med Pediatr Oncol

Complications of Treatment
Cognitive disability in adult patients with brain tumors