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Association of Striatal Dopamine Depletion and Brain Metabolism Changes With Motor and Cognitive Deficits in Patients With Parkinson Disease

Authors
 Han Soo Yoo  ;  Han-Kyeol Kim  ;  Han Kyu Na  ;  Sungwoo Kang  ;  Mina Park  ;  Sung Jun Ahn  ;  Jae-Hoon Lee  ;  Young Hoon Ryu  ;  Chul Hyoung Lyoo 
Citation
 NEUROLOGY, Vol.103(12) : e210105, 2024-12 
Journal Title
NEUROLOGY
ISSN
 0028-3878 
Issue Date
2024-12
MeSH
Aged ; Brain / diagnostic imaging ; Brain / metabolism ; Cognitive Dysfunction / diagnostic imaging ; Cognitive Dysfunction / etiology ; Cognitive Dysfunction / metabolism ; Corpus Striatum / diagnostic imaging ; Corpus Striatum / metabolism ; Cross-Sectional Studies ; Dopamine Plasma Membrane Transport Proteins / metabolism ; Dopamine* / metabolism ; Female ; Fluorodeoxyglucose F18* ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease* / complications ; Parkinson Disease* / diagnostic imaging ; Parkinson Disease* / metabolism ; Positron-Emission Tomography* ; Tropanes
Abstract
Background and objectives: Parkinson disease (PD) shows degeneration of dopaminergic neurons in the substantia nigra and characteristic changes in brain metabolism. However, how they correlated and affect motor and cognitive dysfunction in PD has not yet been well elucidated.

Methods: In this single-site cross-sectional study, we enrolled patients with PD who underwent N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (18F-FP-CIT) PET, 18F-fluorodeoxyglucose (18F-FDG) PET, the Movement Disorder Society-sponsored Unified PD Rating Scale examination, and detailed neuropsychological testing. General linear models and mediation analyses were implemented to investigate the association between striatal dopamine transporter availability, brain metabolism, and parkinsonian motor subscores or domain-specific cognitive scores. Healthy controls (HCs) who underwent 18F-FP-CIT and 18F-FDG PET were also enrolled.

Results: Compared with HCs (n = 38, mean age 67.3 ± 5.9 years; 19 women), patients with PD (n = 143, mean age 69.0 ± 9.0 years; 69 women) characteristically showed relative brain hypermetabolism and hypometabolism that correlated with striatal dopamine transporter availability. As the loss of putaminal dopamine transporter availability increased, brain metabolism relatively increased from the paracentral lobule, pons, and limbic system to the cerebellum and anterior cingulate cortex, whereas brain metabolism relatively decreased from the lateral temporal and frontal cortices to the occipital and inferior parietal cortices. Reduced putaminal dopamine was associated with a higher rigidity subscore by the mediation of relative hypermetabolism in the paracentral lobule (standardized indirect effect, β = -0.070, p = 0.025) and directly associated with a higher bradykinesia subscore (β = -0.274, p = 0.011). Reduced caudate dopamine was associated with a higher axial subscore (β = -0.125, p = 0.004) and lower executive (β = 0.229, p = 0.004), visuospatial (β = 0.139, p = 0.006), and memory (β = 0.140, p = 0.004) domain scores by the mediation of relative brain hypometabolism. The tremor subscore and language and attention scores were not associated with striatal dopamine availability or brain metabolism.

Discussion: Our findings suggest that in PD, striatal dopamine depletion and altered brain metabolism are closely linked, that changes in brain metabolism occur in specific spatial patterns depending on the degree of dopamine depletion, and that both differentially affect motor and cognitive dysfunction depending on each symptom.
Full Text
https://www.neurology.org/doi/10.1212/WNL.0000000000210105
DOI
10.1212/WNL.0000000000210105
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Sung Woo(강성우)
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
Park, Mina(박미나) ORCID logo https://orcid.org/0000-0002-2005-7560
Ahn, Sung Jun(안성준) ORCID logo https://orcid.org/0000-0003-0075-2432
Ryu, Young Hoon(유영훈) ORCID logo https://orcid.org/0000-0002-9000-5563
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Lee, Jae Hoon(이재훈) ORCID logo https://orcid.org/0000-0002-9898-9886
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/201664
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