Causes and mechanisms of cognitive impairment

Histology, disease progression, treatment-related neurotoxicity, neural reorganization, individual psycho-physical conditions, and co-morbidity are factors that determine how severe and which type of cognitive impairment follows from a brain tumour. Brain tumour does not only cause focal neuron disruption, but is also involved in alterations in brain connectivity. When an alteration in amplitude and synchronization of low frequency connectivity is found in combination with toxic and metabolic insults, this can result in whole brain dysfunction. Very important for the onset, progression and severity of the cognitive deficits are the histology and location of the brain tumour. Tucha et al. discovered that in 91% of patients with a brain tumour have deficits in executive functions, memory and attention prior to a surgery (for removing a brain tumour), which states that the deficit is not only the effect of the surgery. Radiotherapy can also be responsible for negative cognitive changes. Klein et al. found that the increase of radiotherapy predicts an increase in severity of the cognitive changes produced by the radiotherapy. Klein et al. also discovered that the changes in executive function and attention were due to hemispheric location and antiepileptic drugs, which means that these deficits were not due to damage from surgery. Studies have shown contradictory results: some studies also show that the radiotherapy has no effect on the brain. This result suggests that the tumour (low-grade glioma, LGG, used here) itself is the most important part for the cognitive decline and radiotherapy can only make it worse or have no effect. But it must be noted that the studies used to make this conclusion lack of baseline evaluations, homogenous groups and are retrospective.

While studying high-grade glioma (HGG) Steinbach et al. and Hottinger et al. found that HGG patients have a decline in attention, information processing and psychomotor speed. Patients with tumour recurrence or patients who had medication with corticosteroids and antiepileptic drugs had the biggest decline. The decline in attention, information processing and psychomotor speed is also found in glioblastoma patients by Corn et al. Longitudinal studies show that specific cognitive impairments can be related to tumour location, but it is the growth of the tumour and the treatment that determine the severity of the cognitive impairments. Additional possible impairments are impairments in motor speed, manual dexterity, memory and executive function, but not verbal memory. Meyers et al. showed that verbal memory was related to survival, adjustments for age, Karnofsky performance status and the number of surgical resections. When people are treated with chemotherapy their cognitive functions can improve or remain stable. But it is hard to distinguish between the effects from radiotherapy and the negative effects from chemotherapy. As a result of surgery the cognitive functions may improve, or they remain the same.

Cognitive patterns

Brain tumours do not always have the same effect on a location in the brain. Sometimes focal deficits are masked because of compensation and substitution from the neural mechanisms (slow-growing tumours) or the focal deficits are surpassed by physical symptoms (high-grade tumours). Absence/presence of a particular psychological-behavioural pattern, can be related to a specific brain area. Frontal tumours lead to problems with working memory, inhibition of interference on ongoing actions, social cognition, risk assessment, decision making, use of external feedback, initiative, abstraction, flexibility and expression. Temporal tumours lead to verbal, comprehension, memory, semantic and social cognition problems. Memory failure can be caused by tumours in the diencephalon and corpus callosum. Visuospatial recognition, semantic competence and social cognition are also affected by occipital-parietal tumours. Occipital-parietal tumours may impair visuospatial recognition, semantic competence, and social cognition. Tumours of the cerebellum cause problems with modulating and checking mental operations. Areas specific for language cause problems with memory, attention, word fluency and verbal learning.

Objectives of neuropsychological assessment

Neuropsychological assessment is done for different reasons. The most common assessment is identification of individual strengths and deficits and the correlation with brain areas. Attention should be paid to the length of the assessment, which may cause fatigue and distress. Which assessment is used differs also in relation to the phase of the disease and treatment. Neuropsychological functioning is often combined with quality of life assessment. Deficits of memory and verbal comprehension can affect how patients report their QOL, but deficits itself can also cause a decline in QOL. Neuropsychological assessments are also used to support prognosis. Test scores may predict future behaviour and survival. Furthermore neuropsychological assessment can be used for non-pharmacological treatment planning (psychological support/therapy).

Neuropsychological testing

To create a full image of the neuropsychological change, most of the time multidimensional tests have to be done. One should also be cautious with pre-structured tests, because of their instability towards specific deficits they cannot give as precise results as tests tailored for clinical and research purpose. It is also important that a neuropsychological test should have standardized procedures, adequate consent/structure/validity/reliability, and have alternative forms. Test results should be showing clinically significant changes, not statistical significant changes. To show these results, baseline (pre surgical) testing must be done.

Meyer and Hess showed that a 40min set of test is enough to predict the radiological progression of brain tumour. When disease-related variables are added to the test battery survival rates can also be predicted. Tests assessing memory, executive function, and memory are the most likely to detect cognitive deficits in adults with tumours. Other studies showed that assessing social cognitive deficits are also very likely to show cognitive deficits because of the lesion itself, seizures or altered brain connectivity (in this case the brain area should be screened).

Non-pharmacological treatment of cognitive deficits

Cognitive rehabilitation, using retraining or compensation strategies, has been showing improvement in attention and memory for patients with a brain tumour. Although the studies performed on this topic lacked randomized study designs, control group, and follow-up evaluations, because of the importance of the cognitive impairment to the patient to the prognosis, careful neuropsychological assessment and non-pharmacological treatment remains very important.