Review Question - QID 108758

An 83-year-old man is brought to the emergency department by his daughter due to confusion over the last 2 weeks. The patient initially became less talkative than usual before starting to confuse her with her sister. The patient also could not remember what day of the week it was and he was out of groceries and likely had been for several days when visited. While she was talking to him, he fell asleep and was difficult to rouse. The patient is unable to provide a clear history. He has a medical history of hypertension, glaucoma, and osteoarthritis in his left knee that requires him to walk with a cane. He takes hydrochlorothiazide, timolol eyedrops, and occasional acetaminophen. His temperature is 98.5° F (36.9° C), blood pressure is 122/74 mmHg, pulse is 75/min, and respirations are 14/min. The patient is lethargic but arousable, oriented only to person, and disheveled. Neurologic exam reveals intact cranial nerves, 1+ deep tendon reflexes throughout, and 4/5 strength in all extremities. There is a 3 x 5 cm green-blue area of ecchymosis on the lateral aspect of his left knee. A CT of the head without contrast is performed and shown in Figure A. Which of the following factors plays the earliest role in the progression towards this patient’s presentation?