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Interrelation of striatal dopamine, brain metabolism and cognition in dementia with Lewy bodies

 Han Soo Yoo  ;  Seong Ho Jeong  ;  Kyeong Taek Oh  ;  Sangwon Lee  ;  Young H Sohn  ;  Byoung Seok Ye  ;  Mijin Yun  ;  Phil Hyu Lee 
 BRAIN, Vol.145(12) : 4448-4458, 2022-12 
Journal Title
Issue Date
Brain / metabolism ; Cognition ; Dopamine / metabolism ; Dopamine Plasma Membrane Transport Proteins* / metabolism ; Fluorodeoxyglucose F18 / metabolism ; Humans ; Lewy Body Disease* / metabolism ; Positron Emission Tomography Computed Tomography
brain metabolism ; cognition ; dementia with Lewy bodies ; dopamine transporter
Dementia with Lewy bodies (DLB), the second most common neurodegenerative dementia, is characterized by cognitive decline, fluctuation of cognition and alertness, visual hallucinations, rapid eye movement sleep behaviour disorder and parkinsonism. Imaging biomarkers are of great importance in diagnosing patients with DLB and associated with characteristic clinical features including cognitive decline. In this study, we investigate interrelation between nigrostriatal dopamine depletion, brain metabolism and cognition in DLB. We enrolled 55 patients with probable DLB (15 with prodromal DLB and 40 with DLB) and 13 healthy controls. All subjects underwent N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane PET/CT, 18F-fluorodeoxyglucose PET/CT, 18F-florbetaben PET/CT and detailed neuropsychological testing. The relationship between striatal dopamine transporter availability and regional brain metabolism was assessed using general linear models, and the effect of striatal dopamine transporter availability and brain metabolism on specific cognitive function was evaluated by multivariate linear regression analysis. Path analyses were used to evaluate the relationship between striatal dopamine transporter availability, fluorodeoxyglucose uptake and cognitive function scores. Additionally, a linear mixed model was used to investigate the association between baseline dopamine transporter availability or brain metabolism and longitudinal cognitive decline. Independent of amyloid deposition, caudate and putamen dopamine transporter availabilities were positively correlated with brain metabolism in the DLB-specific hypometabolic regions, most prominently in the occipital and lateral parietal cortices. Both reduced caudate dopamine and brain hypometabolism were associated with low z-scores of Rey-Osterrieth Complex Figure Test copy, Seoul Verbal Learning Test immediate recall and Controlled Oral Word Association Test (COWAT)-animal. Path analyses showed that the effect of reduced caudate dopamine on the Rey-Osterrieth Complex Figure Test copy z-score was completely mediated by brain hypometabolism, whereas it affected the Seoul Verbal Learning Test immediate recall z-score both directly and via the mediation of brain hypometabolism. Caudate dopamine depletion was directly associated with the COWAT-animal z-score, not mediated by brain hypometabolism. Both baseline caudate dopamine transporter availability and brain hypometabolism were associated with longitudinal cognitive decline, with brain hypometabolism being more relevant. Our findings suggest that in DLB, striatal dopaminergic depletion and brain hypometabolism are closely related, and they differentially affect cognitive dysfunction in an item-specific manner. Additionally, brain hypometabolism would be more relevant to longitudinal cognitive outcomes than striatal dopaminergic degeneration.
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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
Yonsei Authors
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Ye, Byoung Seok(예병석) ORCID logo https://orcid.org/0000-0003-0187-8440
Oh, Kyeong Taek(오경택) ORCID logo https://orcid.org/0000-0002-6857-0945
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
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