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Background: A dual-syndrome hypothesis, which states the cognitive impairments in Parkinson's disease (PD) are attributable to frontostriatal dopaminergic dysregulation and cortical disturbance-each associated with attention/executive and memory/visuospatial dysfunction, respectively-has been widely accepted. This multisystem contribution also underlies highly heterogeneous progression rate to dementia., Methods: Nondemented PD patients who underwent [ 123 I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([ 123 I]FP-CIT) SPECT and neuropsychological examinations were enrolled. Patients who agreed to participate and age- and sex-matched healthy controls (HCs) also underwent 7-T MRI. Patients were classified as cognitively normal (PD-CN) or mild cognitive impairment (PD-MCI) following the level II criteria of Movement Disorder Society Guideline., Results: A total of 155 patients (PD-CN/PD-MCI 74/81) were enrolled, whereas 76 patients (PD-CN/PD-MCI 35/41) and 56 HCs underwent 7 T-MRI. The caudate [ 123 I]FP-CIT uptake in PD was correlated with the performance of attention/working memory (trail-making test [TMT]-A and symbol digit modality test) and executive (TMT-B) domains. In contrast, the regional cortical thickness in the left frontotemporal and right frontal lobes in PD was correlated with performance of memory (Hopkins verbal learning test-revised delayed recall) and visuospatial (judgment of line orientation) domains. Moreover, compared to 37 HCs with a Montreal Cognitive Assessment score of >25, PD-CN patients showed broad occipitoparietal cortical thinning., Conclusions: We demonstrated distinctive impairments of dopaminergic frontostriatal deficits and cortical degeneration as neural bases for the dual-syndrome hypothesis. Our findings suggest that occipitoparietal lobe thinning occurs at a cognitively normal stage, and additional frontotemporal lobe thinning underlies impairments in the memory and visuospatial domains at the PD-MCI stage., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Nowadays, presynaptic dopaminergic positron emission tomography, which assesses deficiencies in dopamine synthesis, storage, and transport, is widely utilized for early diagnosis and differential diagnosis of parkinsonism. This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism. We conducted a thorough literature search using reputable databases such as PubMed and Web of Science. Selection criteria involved identifying peer-reviewed articles published within the last 5 years, with emphasis on their relevance to clinical applications. The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis. Moreover, when employed in conjunction with other imaging modalities and advanced analytical methods, presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker. This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion. In summary, the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials, ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)