Purpose <p>While many studies have explored the link between biomarkers and cognitive decline in Parkinson’s disease (PD), a more comprehensive approach is needed, combining striatal dopamine depletion, cerebral glucose metabolism, and cognitive assessments. In this study, we investigated the relationships between striatal dopamine transporter (DAT) uptake, cerebral glucose hypometabolism, and cognition, as well as the potential progression pattern of these changes in PD.</p> Methods <p>We enrolled 62 patients with PD and 33 healthy controls. The subjects underwent N-(3-[¹⁸F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) PET/CT, [¹⁸F] fluorodeoxyglucose (FDG) PET/CT, and detailed neuropsychological testing. The mean standard uptake value ratio (SUVR) value of the regions showing significantly lower metabolism in PD patients was defined as SUVR_[hypo]. The relationship between striatal DAT uptake and SUVR_[hypo] was assessed using general linear models, while their impact on cognitive function was evaluated with multivariate linear regression. Additionally, the pattern of their changes was assessed using an event-based model.</p> Results <p>Compared to the control group, PD patients exhibited glucose hypometabolism in specific cortical regions. DAT uptake in the anterior and posterior putamen was positively correlated with SUVR_[hypo]. Decreased DAT uptake in the anterior putamen and caudate nucleus was associated with lower z-score in visuospatial function. Decreased DAT uptake in the posterior and anterior putamen occurred first, followed by PD-related cerebral hypometabolism, and visuospatial function.</p> Conclusion <p>This study highlights the interconnectedness of dopaminergic depletion, cerebral glucose hypometabolism, and visuospatial dysfunction, proposing that striatal DAT uptake may serve as an early biomarker for cerebral hypometabolism and cognitive impairment in PD.</p>