The aim of the study was to investigate the association between postoperative delirium (POD) and in vivo markers of Alzheimer's disease pathology in nondemented hip fracture surgery patients. POD was assessed with the Confusion Assessment Method. Amyloid load was quantified on (18)F-Flutemetamol positron emission tomography images as standardized uptake value ratio. Secondary outcome measures were gray matter volumes, white matter integrity, and functional connectivity at rest. All the patients with POD (POD+, N = 5) were amyloid negative (standardized uptake value ratio <0.59), whereas 6 out of 11 patients without POD (POD-) showed brain amyloid positivity. POD+ compared to POD- displayed: lower gray matter volumes in the amygdala (p = 0.003), in the middle temporal gyrus and in the anterior cingulate cortex (p < 0.001), increased diffusivity in the genu of the corpus callosum and in the anterior corona radiata (p < 0.05), and higher functional connectivity within the default mode network (p < 0.001). POD patients showed altered gray and white matter integrity in the fronto-limbic regions in absence of brain amyloidosis. Based on this preliminary investigation, delirium pathophysiology might be independent of Alzheimer's disease. Future studies on larger samples are needed to confirm this hypothesis.