Objective: To delineate the pattern of nigrostriatal dopaminergic dysfunction in iNPH, explore inter-individual heterogeneity, and evaluate its association with clinical features and long-term outcomes.

Background: Idiopathic normal pressure hydrocephalus (iNPH) frequently presents with parkinsonism and may exhibit dopaminergic deficits on molecular imaging. However, the specific pattern of nigrostriatal involvement and its clinical relevance remain insufficiently characterized.

Method: We enrolled 23 patients with iNPH, 29 with progressive supranuclear palsy (PSP), 23 with Parkinson’s disease (PD), and 17 healthy controls (HC). All participants underwent ¹⁸F-FP-DTBZ PET/CT scanning. Patients with iNPH received a levodopa challenge test and brain MRI evaluation. The caudate-to-posterior putamen (C/PP) ratio was calculated to stratify iNPH into two subgroups (C/PP <1 vs >1). A five-year longitudinal follow-up was conducted, with all-cause mortality as the primary outcome.

Results: In iNPH, striatal ¹⁸F-FP-DTBZ uptake was reduced compared with HC (P < 0.001). The caudate involvement was relatively prominent, whereas the anterior and posterior putamen involvement was milder than in PSP and PD. The mean C/PP ratio in iNPH was approximately 1, contrasting with values >1 in PSP and PD. Substantia nigra uptake was preserved in iNPH compared with PSP and PD, and showed no significant difference with HC (P=0.492). Based on C/PP ratio, iNPH were divided into subgroup 1 (C/PP<1) and subgroup 2 (C/PP>1). Subgroup 2 showed greater levodopa responsiveness (P = 0.009), and substantia nigra uptake showed a decreasing trend but did not reach statistical significance. During the 5-year follow-up, subgroup 2 had a higher frequency of comorbid neurodegenerative disorders compared with subgroup 1(62.5% vs 13.3%) and an earlier decline in survival probability, although the overall survival did not differ significantly between groups (log-rank P = 0.337).

Conclusion: iNPH demonstrates mild-to-moderate striatal dopaminergic impairment with predominant caudate involvement and relative preservation of the substantia nigra. A distinct iNPH subtype with prominent posterior putaminal involvement shows better levodopa responsiveness and may reflect underlying neurodegenerative comorbidity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/nigrostriatal-dopaminergic-impairment-patterns-in-idiopathic-normal-pressure-hydrocephalus-identified-by-18f-fp-dtbz-pet-a-5-year-longitudinal-study/