Hippocampal Perfusion Affects Motor and Cognitive Functions in Parkinson Disease: An Early Phase 18F-FP-CIT Positron Emission Tomography Study

Abstract

Objectives: We investigated whether hippocampal perfusion changes are associated with cognitive decline, motor deficits, and the risk of dementia conversion in patients with Parkinson's disease (PD).

Methods: We recruited patients with newly diagnosed PD and healthy participants who underwent dual-phase 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET) scans. Patients were classified into three groups according to hippocampal standard uptake value ratios (SUVRs): 1) the PD hippocampal hypoperfusion group (1 standard deviation [SD] below the mean hippocampal SUVR of healthy controls; PD-hippo-hypo), 2) the 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 the risk of dementia conversion among the groups.

Results: We included 235 patients (PD-hippo-hypo: n= 21; PD-hippo-normal: n= 157; and 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 than 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.

Interpretation: Hippocampal 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.