**5.2. Predisposing factors**

Older ages more than 60 years and in some studies more than 40 years old have increased risk to develop leukoencephalopathy specifically in patients with genetic predisposition to leukoencephalopathy [75] with subsequent cognitive deficit. Also patient with white matter disease such as multiple sclerosis have increased risk, also vascular diseases such as hyper‐ tention carry risk [76].

Beside the previous patient-related factors, also there are factors related to treatment include the dose of RT received, dose per fraction and volume of irradiated brain, 5% of patients treated with more than 5000 cGy develop radiation necrosis [77], high radiation dose increases the risk of leukoencephalopathy, daily doses >200 cGy have a significantly increased risk of cogni‐ tive damage [75]. The large irradiated volume of brain tissues carries increased risk of cognitive impairment, and whole brain radiation has threefold to fourfold increased risk of encephal‐ opathy [76].

Additional treatments to RT such as chemotherapy have increased risk on cognition than RT alone, systemic and intrathecal treatments have been implicated. Methotrexate chemothera‐ py when received intravenously or intrathecally after cranial irradiation has an effect on cognition in children and also on adults [78].
