Complications of TreatmentCognitive disability in adult patients with brain tumors
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.
References (98)
- et al.
International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer
Lancet Oncol
(2011) - et al.
Mini-mental state. A practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
(1975) - et al.
Cognitive function of patients with brain tumor in pre- and postoperative stage
Surg Neurol
(2008) - et al.
Therapeutic irradiation and brain injury
Int J Radiat Oncol
(1980) - et al.
Early clinical and neuroradiological worsening after radiotherapy and concomitant temozolomide in patients with glioblastoma: tumour progression or radionecrosis?
Clin Neurol Neurosurg
(2009) - et al.
Cognitive deficits in adult patients with brain tumours
Lancet Neurol
(2004) - et al.
Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?
Cancer Lett
(2016) - et al.
A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study
Lancet Oncol
(2017) - et al.
Finding the genetic determinants of adverse reactions to radiotherapy
Clin Oncol
(2014) - et al.
Cognitive function after chemotherapy in adults with solid tumours
Crit Rev Oncol Hematol
(2007)
Neurobiological basis of chemotherapy-induced cognitive impairment: a review of rodent research
Neurosci Biobehav Rev
ERP amplitude and latency in breast cancer survivors treated with adjuvant chemotherapy
Clin Neurophysiol
Lithium-mediated neuroprotection during cranial irradiation: a phase I trial
Int J Radiat Oncol
The AT1 receptor antagonist, L-158,809, prevents or ameliorates fractionated whole-brain irradiation-induced cognitive impairment
Int J Radiat Oncol
Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiation Therapy (WBRT): first report of RTOG 0614, a placebo-controlled, double-blind, randomized trial
Int J Radiat Oncol
Functional recovery of patients with brain tumor or acute stroke after rehabilitation: a comparative study
J Clin Neurosci
Exercise training improves sleep quality in middle-aged and older adults with sleep problems: a systematic review
J Physiother
Tai Chi effects on neuropsychological, emotional, and physical functioning following cancer treatment: a pilot study
Complement Ther Clin Pract
Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial
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
A link between vascular damage and cognitive deficits after whole-brain radiation therapy for cancer: a clue to other types of dementia?
Drug Discov Ther
Cited by (43)
Understanding experiences of cognitive decline and cognitive assessment from the perspectives of people with glioma and their caregivers: A qualitative interview study
2024, International Journal of Nursing Studies AdvancesEffect of Comorbid Depression on Surgical Outcomes After Craniotomy for Malignant Brain Tumors: A Nationwide Readmission Database Analysis
2020, World NeurosurgeryCitation 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.
Cognitive impairment following radiation to hippocampus and other brain structures in adults with primary brain tumours
2020, Radiotherapy and OncologyDifferential diagnoses in dementia development
2024, Deutsche Medizinische WochenschriftNeurorehabilitation for Adults with Brain and Spine Tumors
2024, Seminars in NeurologyA literature review of outcome and treatment options after acquired brain injury: Suggestions for adult offenders using knowledge from the general population
2024, Criminal Behaviour and Mental Health