Boniface VIII (Benedetto Caetani, c. 1230–1303) is considered one of the most famous popes of the Middle Ages. He is mainly known for the celebration of the first Catholic Jubilee (1300) and for his disputes with the French King Philip IV the Fair (1268–1314) on papal supremacy that resulted first in the writing of the bull Unam Sanctam (1302), declaring the supremacy of spiritual power over temporal power, and then in a French kidnapping of Boniface. After a long exchange of reciprocal accusations and excommunications, on 7 September 1303, a French army guided by Guillaume de Nogaret (1260–1313) and Giacomo Colonna (1270–1329) attacked the palace of Boniface VIII in Anagni and imprisoned the pope, demanding his resignation. He was allegedly beaten and humiliated; even though there is no evidence of the pope being slapped, this episode is commonly known as the Schiaffo di Anagni (Anagni's Slap). After 3 days of captivity, he was released following the uprising of his hometown Anagni against the captors. This episode caused a stir even among the strenuous opponents of the pope. For example, the Italian poet Dante Alighieri (1265–1321), who was openly in contrast with Boniface's abuse of temporal power, criticised the Anagni incident in his masterpiece ‘Divine Comedy’.

Now 73 years old, Boniface VIII never recovered and died within a few weeks on 11 October. In the last days of life, the pope suffered from an acute confusional state (extra mentem cordis positus); he allegedly appeared disoriented, possibly suffering from seizures and perceptual disturbances, particularly visual and auditory hallucinations. Boniface floated from a hyperactive to a hypoactive state. He showed aggressive behaviour towards other people as well as himself – he allegedly bit his own arms and hands – or depressed and drowsy, so dying angry and desperate (papa Bonifatius obiit non bono modo, sed rabiosus et desperatus de Deo).

The detailed description of the terminal symptoms of Boniface VIII suggest that he may have been affected by acute delirium. According to customary definitions of delirium this condition requires a fluctuating and acutely developed disturbance in attention and awareness, an additional cognitive disturbance and evidence of one or more underlying organic causes. Older age, dementia, functional disabilities and a high burden of coexisting conditions are common predisposing factors. High pain levels, anaemia, infections, acute illness and acute exacerbation of chronic illness are some of the most commonly reported precipitating factors.

In Boniface's case, delirium may have been a consequence of brain injuries resulting from the brutal beatings. A cerebrovascular accident may have resulted in a similar confusional state as well. Finally, since the pope suffered from kidney stones over several decades, it may also be hypothesised that delirium was caused by end-stage kidney disease. Whatever the disease that brought the pope to death, his last days of agony represent one of the most ancient accurate descriptions of acute delirium in an elderly person.