Longitudinal SPECT Assessment of Regional Cerebral Perfusion Associated with Nicergoline Use in Parkinson’s Disease Without Dementia: An Exploratory Observational Study

Background/Objectives: Cerebral hypoperfusion has been reported in Parkinson’s disease (PD), including in patients without dementia. We explored whether long-term nicergoline use was associated with longitudinal changes in relative regional cerebral blood flow (rCBF) and clinical outcomes in non-demented PD. Methods: Thirty patients with idiopathic PD without dementia underwent Unified Parkinson’s Disease Rating Scale (UPDRS) assessment and 99mTc-ethyl cysteinate dimer brain perfusion SPECT at baseline and again after 2–4 years. Eighteen patients received nicergoline (30 mg twice daily) with standard dopaminergic treatment, whereas 12 received dopaminergic treatment without nicergoline. Treatment allocation was non-randomized. Longitudinal SPECT change images were analyzed in SPM12. The voxel-wise group comparison used p < 0.001 uncorrected with a cluster extent threshold of ≥50 voxels and was considered exploratory because no correction for multiple comparisons was applied. Results: Baseline clinical characteristics did not differ significantly between groups, although age was numerically higher in the nicergoline group (72.4 ± 6.44 vs. 66.8 ± 9.14 years; p = 0.057). Changes in UPDRS scores, Hoehn and Yahr stage, and levodopa equivalent daily dose did not differ significantly between groups. A single 76-voxel cluster showed a greater relative perfusion increase in the right temporal fusiform cortex (Brodmann area 37; peak MNI coordinate 34, −40, −22; t = 4.07; uncorrected p < 0.001) in the nicergoline group. Conclusions: Long-term nicergoline exposure was associated with an uncorrected group-level difference in right fusiform relative perfusion without corresponding clinical improvement. Because the finding was based on a small, non-randomized cohort and an uncorrected voxel-wise threshold, it should not be interpreted as evidence of therapeutic efficacy or a cholinergic/cognitive benefit. Larger randomized studies with multiplicity control and clinically relevant cognitive outcomes are required.