Abstract BACKGROUND Glioblastoma (GBM) and Alzheimer’s disease (AD) are frequent among the elderly: about 50% of all GBM patients are 65 years or older, and 5–10% of people above this age threshold suffer from AD. MATERIAL AND METHODS We describe the case of an elderly patient with newly diagnosed GBM who developed a rapidly progressive severe dementia immediately following concomitant radio-chemotherapy. A purposed retrospective analysis of the surgical sample revealed Alzheimer pathology. RESULTS A 69-year old woman with no relevant past-medical history was diagnosed with a right temporo-parietal GBM on May 2017, with wild-type IDH1R132H gene and methylated MGMTP. After complete resection she received radiotherapy (60 Gy in 30 fractions) and concomitant chemotherapy with Temozolomide 75 mg/m2/day. During the last weeks of concomitant radio-chemotherapy and further on the patient developed a progressive neurological worsening with severe cognitive dysfunction, gait impairment and sphincter incontinence, becoming severely disabled and requiring continuous assistance. Brain MRI exams showed no signs of tumor recurrence, with focal white matter changes consisting on T2/FLAIR hyperintensities within the radiation field, enlarged sulci and ventriculomegaly. Underlying infectious and metabolic disorders, non-convulsive epileptic status and normal-pressure hydrocephalus were ruled out. Facing this situation the patient relatives were purposely asked for previous cognitive symptoms, and described very mild complaints of short-term memory loss during the previous year. Aiming at investigating the possibility of an underlying AD, focused examination of the surgical sample revealed the presence of frequent neuritic plaques, a neuropathological hallmark of AD. The patient developed a severe dementia with akinetic mutism by September 2017. Without evidence of tumor recurrence despite lack of adjuvant chemotherapy, she died of aspiration pneumonia on January 2019. CONCLUSION A unique retrospective study including elderly GBM patients treated only with surgery revealed that Alzheimer disease pathology was present in 42% of them. This case illustrates the need for actively addressing the previous cognitive status of elderly patients with GBM. Histopathological assessment of Alzheimer pathology might also be considered in this specific population. In positive cases, particularly in those with methylated MGMTP, radiotherapy should be avoided and treatment alone with Temozolomide might be considered.