Relationship between VMAT2-PET and DAT-SPECT caudate binding and Parkinson's disease cognitive decline

• Published in: Parkinsonism & related disorders Vol. 139; p. 108008
• Main Authors: Hamo, Mohammad, Anyanwu, Nicole, Long, Isabel, Gupta, Rishabh, Bermudez, Rocio, Subramanian, Deeptha, Qian, Helen, Dhima, Kaltra, Bick, Sarah K.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2025
• Subjects: Cognitive decline; Cognitive impairment; Dopamine transporter; Montreal cognitive assessment; Parkinson's disease; Vesicular monoamine transporter type 2; Cognitive decline; Dopamine transporter; Parkinson's disease; Montreal cognitive assessment; Vesicular monoamine transporter type 2; Cognitive impairment
• ISSN: 1353-8020
• DOI: 10.1016/j.parkreldis.2025.108008

Dopamine transporter (DAT) imaging can help diagnose Parkinson's disease (PD), and decreased caudate binding predicts cognitive decline. Studies suggest vesicular monoamine transporter type 2 (VMAT2) imaging is more sensitive in detecting striatal changes associated with PD motor symptoms. Our hypothesis is that lower VMAT2 caudate binding is correlated with future cognitive decline in PD. We utilized clinical and imaging data from the Parkinson's Progression Markers Initiative (PPMI). We evaluated the relationship between baseline VMAT2 and DAT caudate binding and future change in Montreal Cognitive Assessment (MoCA) score using linear regression. To evaluate localization of findings we performed similar analysis with VMAT2 and DAT putamen and most and least affected caudate binding. We also categorized patients into groups of normal and reduced VMAT2 and DAT caudate binding and compared baseline and follow up characteristics between groups. Among 54 subjects with follow up data, baseline VMAT2 caudate binding correlated with change in MoCA score, while DAT did not (r = 0.280, p = 0.0164 and r = 0.189, p = 0.410 respectively). Baseline VMAT2 putamen binding also correlated with change in MoCA score (p = 0.0236, r = 0.23). Reduced VMAT2 caudate binding groups had higher motor severity score at baseline and lower cognitive scores on follow-up (p = 0.0015), while DAT did not (p = 0.174). Patients with reduced VMAT2 caudate but not putamen binding had significantly greater decline in MoCA score (caudate p = 0.0015, putamen p = 0.179). Reduced caudate VMAT2 binding may predict future cognitive decline, and in our patient population, was more sensitive than caudate DAT binding in predicting the magnitude of decline. •Low monoamine caudate binding may predict cognitive decline in Parkinson's.•Monoamine transporter caudate binding may be more sensitive than dopamine transporter binding.•Imaging at diagnosis may forecast cognitive changes in Parkinson's disease.•Imaging biomarkers offer insight to Parkinson's-related cognitive progression.