ObjectiveWe investigated whether hippocampal perfusion changes are associated with cognitive decline, motor deficits, and the risk of dementia conversion in patients with Parkinson disease (PD).MethodsWe recruited patients with newly diagnosed and nonmedicated PD and healthy participants who underwent dual phase ¹⁸F‐N‐(3‐fluoropropyl)‐2β‐carboxymethoxy‐3β‐(4‐iodophenyl) nortropane positron emission tomography scans. Patients were classified into 3 groups according to hippocampal perfusion measured by standard uptake value ratios (SUVRs): (1) PD hippocampal hypoperfusion group (1 standard deviation [SD] below the mean hippocampal SUVR of healthy controls; PD‐hippo‐hypo), (2) PD hippocampal hyperperfusion group (1 SD above the mean; PD‐hippo‐hyper), and (3) the remaining patients (PD‐hippo‐normal). We compared the baseline cognitive performance, severity of motor deficits, hippocampal volume, striatal dopamine transporter (DAT) availability, and risk of dementia conversion among the groups.ResultsWe included 235 patients (PD‐hippo‐hypo, n = 21; PD‐hippo‐normal, n = 157; PD‐hippo‐hyper, n = 57) and 48 healthy participants. Patients in the PD‐hippo‐hypo group were older and had smaller hippocampal volumes than those in the other PD groups. The PD‐hippo‐hypo group showed less severely decreased DAT availability in the putamen than the other groups despite similar severities of motor deficit. The PD‐hippo‐hypo group had a higher risk of dementia conversion compared to the PD‐hippo‐normal (hazard ratio = 2.59, p = 0.013) and PD‐hippo‐hyper (hazard ratio = 3.73, p = 0.006) groups, despite similar cognitive performance at initial assessment between groups.InterpretationHippocampal hypoperfusion may indicate a reduced capacity to cope with neurodegenerative processes in terms of the development of motor deficits and cognitive decline in patients with PD. ANN NEUROL 2024;95:388–399