**1. Introduction**

#### **1.1. Background**

The term intellect designates the totality of the mental or cognitive operations that comprise human thought, and the higher cortical functions that make up the human mind. Memory is a specific cognitive function: the storage and retrieval of information. Other "higher" functions, such as language, calculations, spatial topography and reasoning, music, and creativity, all represent the functions of specific brain systems [1].

Cognitive functioning of brain tumor patients is an increasingly important outcome measure, because cognitive impairments can have a large impact on self-care, social and professional functioning, and consequently on quality of life (QOL) [2]. Patients with brain tumors often experience cognitive dysfunction associated with the disease itself and its treatment, as well, including surgery, radiotherapy (RT), and chemotherapy. Cognitive dysfunction has been recognized as the most frequent complication among long-term survivors. Despite the many advances made in the treatment modalities and surgical techniques, primary malignant brain cancer is a devastating illness, characterized by poor survival rates and significant morbidity as the disease progresses [3]. For many patients, cognitive changes are part of the disease process, but the pattern of impairment can vary markedly in different patients.

Resection of brain tumors may result in improvement of cognitive functions. Teixidor et al. [4] reported long-term improvement of verbal memory, after a transient immediate postopera‐ tive worsening, following frontal premotor and anterior temporal area resection, usually after a transient immediate postoperative worsening. Cognitive improvement has also been observed after surgical resection of high-grade gliomas [5], and in some studies stable, cognitive performance was observed after brain tumor resection, for instance, patients with tumors of the third ventricle [6].

Specific cognitive domain deficits after brain tumor removal were observed in some studies. A study conducted by Goldstein et al. [7] reported minimal deterioration in attention after right parenchymal frontal or precentral tumors resection. Another study [8] concluded that right rather than left prefrontal cortex resection was associated with, stroop performance test, selective attentional decline.

Radiation-induced cognitive impairment in some series is reported to occur in up to 50–90% of adult patients with brain tumor who survive >6 months after fractionated partial or wholebrain irradiation [9]. Moreover, because patients with brain tumor are surviving longer because of improved radiation therapy techniques and systemic therapies [10], the patient population experiencing these significant late effects is growing rapidly. Radiation-induced cognitive impairment is marked by decreased verbal memory, spatial memory, attention, and novel problem-solving ability [11]. Modern radiation therapy techniques have resulted in decreased acute and early delayed brain injury as well as late demyelination and white matter necrosis with less cognitive functional deficits, including progressive memory impairments, attention, and executive function that finally led to less impact on QOL of most survivors [12].

Neurocognitive sequelae of chemotherapy are less well documented than radiation effects [13]. Chemotherapy-related neurotoxicity to the central nervous system may be increased by intraarterial administration, especially in combination with osmotic blood–brain barrier disrup‐ tion, meant to increase the local concentration of chemotherapy in the brain [14]. Neurotoxicity may also be increased by chemotherapy given after, or even during, RT [15]. Primary central nervous system lymphoma is chemoresponsive, such as anaplastic oligodendroglioma (AO) and oligoastrocytoma (OA) tumors, chemotherapeutic agents are often ineffective due to limited ability to cross the BBB. Use of radiation therapy is often associated with significant neurotoxicity [16].

Advances in neurosurgery, chemotherapy, and RT are helping to a great extent in prevent‐ ing cognitive deficit. Prevention depends in part on being able to predict the risky factors [17].
