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Association of Relative Brain Hyperperfusion Independent of Dopamine Depletion With Motor Dysfunction in Patients With Parkinson Disease

Authors
 Han Soo Yoo  ;  Young-Gun Lee  ;  Young H Sohn  ;  Mijin Yun  ;  Jungho Cha  ;  Phil Hyu Lee 
Citation
 NEUROLOGY, Vol.103(12) : e210077, 2024-12 
Journal Title
NEUROLOGY
ISSN
 0028-3878 
Issue Date
2024-12
MeSH
Aged ; Brain* / diagnostic imaging ; Brain* / metabolism ; Cerebrovascular Circulation / physiology ; Disease Progression ; Dopamine Plasma Membrane Transport Proteins / metabolism ; Dopamine* / metabolism ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parkinson Disease* / diagnostic imaging ; Parkinson Disease* / metabolism ; Parkinson Disease* / physiopathology ; Positron-Emission Tomography* ; Tropanes*
Abstract
Background and objectives: Parkinson disease (PD) exhibits a characteristic pattern of brain perfusion or metabolism, thereby being considered network disorder. Using dual-phase N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) PET, we investigated the role of brain perfusion in motor symptoms and disease progression, independent of striatal dopamine depletion.

Methods: We recruited patients with de novo PD and healthy controls (HCs) who underwent dual-phase 18F-FP-CIT PET and brain MRI. All patients underwent the Unified PD Rating Scale (UPDRS) and were followed up for ≥5 years. A subset of patients (n = 51) underwent follow-up UPDRS and brain MRI. Early-phase images evaluated brain perfusion, while delayed-phase images evaluated dopamine transporter availability. We compared early-phase 18F-FP-CIT uptakes (SUVRE) between PD and HC groups. Then, we investigated the association of SVURE and delayed-phase 18F-FP-CIT uptakes (SUVRD) with motor symptoms in PD. Standardized residuals (SRs) of the SUVRE in the hyperperfusion region (SUVRE-HYPER) were obtained from the linear regression of the SUVRD in the posterior putamen (SUVRD-PP), the main region of dopamine deficit. Subsequently, we investigated the association of the SR with baseline and longitudinal motor symptoms and brain atrophy.

Results: Compared with HC (n = 30), patients with PD (n = 168) showed relative hyperperfusion in the primary motor cortex, thalamus, pons, hippocampus, and cerebellum and relative hypoperfusion in the prefrontal and temporo-parieto-occipital cortices, which is consistent with a PD-related metabolic pattern. Motor symptoms were negatively correlated with SUVRD-PP (standardized β = 0.402, p < 0.001) and positively correlated with SUVRE-HYPER (standardized β = 0.292, p < 0.001), but not with SUVRE in the hypoperfusion regions. Regardless of SUVRD-PP, SUVRE-HYPER was independently associated with motor dysfunction, especially rigidity (standardized β = 0.214, p = 0.012). The SR of SUVRE-HYPER was significantly associated with the UPDRS part III total score. Longitudinally, the baseline SR of SUVRE-HYPER was not associated with long-term motor complications but with an increase in the UPDRS part III total score (p = 0.017) and a decrease in brain volume.

Discussion: These results suggest that aberrant relative brain hyperperfusion, independent of striatal dopamine depletion, was associated with baseline and longitudinal motor deficits and progression of neurodegeneration in PD.
Full Text
https://www.neurology.org/doi/10.1212/WNL.0000000000210077
DOI
10.1212/WNL.0000000000210077
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
Yonsei Authors
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Yun, Mijin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/201686
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