Longitudinal FDG-PET Metabolic Change Along the Lewy Body Continuum

IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY
Daniel Ferreira, Scott A. Przybelski, Timothy G. Lesnick, Patricia Diaz-Galvan, Christopher G. Schwarz, Melissa M. Murray, Dennis W. Dickson, Aivi Nguyen, Ross R. Reichard, Matthew L. Senjem, Jeffrey L. Gunter, Clifford R. Jack, Paul H. Min, Manoj K. Jain, Toji Miyagawa, Leah K. Forsberg, Julie A. Fields, Rodolfo Savica, Jonathan Graff-Radford, Vijay K. Ramanan, David T. Jones, Hugo Botha, Erik K. St. Louis, David S. Knopman, Neill R. Graff-Radford, Gregory S. Day, Tanis J. Ferman, Walter K. Kremers, Ronald C. Petersen, Bradley F. Boeve, Val J. Lowe, Kejal Kantarci
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引用次数: 0

Abstract

ImportanceAlthough 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established cross-sectional biomarker of brain metabolism in dementia with Lewy bodies (DLB), the longitudinal change in FDG-PET has not been characterized.ObjectiveTo investigate longitudinal FDG-PET in prodromal DLB and DLB, including a subsample with autopsy data, and report estimated sample sizes for a hypothetical clinical trial in DLB.Design, Setting, and ParticipantsLongitudinal case-control study with mean (SD) follow-up of 3.8 (2.3) years. Cases were recruited consecutively between 2007 and 2022 at a referral center and among the population. Patients with probable DLB or mild cognitive impairment with Lewy bodies (MCI-LB) were included. Individuals without cognitive impairment were included from a population-based cohort balanced on age and sex for comparison. All participants completed at least 1 follow-up assessment by design.ExposurePatients with MCI-LB and DLB.Main Outcomes and MeasuresRate of change in FDG-PET was assessed as standardized uptake value ratios (SUVr). Clinical progression was assessed with the Clinical Dementia Rating Sum of Boxes (CDR-SB) score.ResultsThirty-five patients with probable DLB, 37 patients with MCI-LB, and 100 individuals without cognitive impairment were included. The mean (SD) age of the DLB and MCI-LB groups combined (n = 72) was 69.6 (8.2) years; 66 patients (92%) were men and 6 (8%) were women. At follow-up, 18 participants (49%) with MCI-LB had progressed to probable DLB. Patients with MCI-LB had a faster decline in FDG-SUVr, compared with that of participants without cognitive impairment, in the posterior cingulate, occipital, parietal, temporal, and lateral frontal cortices. The same regions showed greater metabolic decline in patients with DLB than in participants without cognitive impairment, with the addition of anterior-middle cingulate, insula, and medial frontal orbital cortices. Rates of change in FDG-PET in these brain regions were combined into a region of interest (ROI) labeled longitudinal FDG-PET LB meta-ROI. The rate of change in FDG-SUVr in the meta-ROI correlated with the rate of change in CDR-SB, and sample size estimates were reported for potential clinical trials in DLB. Findings were confirmed in the subsample with neuropathologic confirmation (n = 20).Conclusions and RelevanceThis study found that brain hypometabolism begins to evolve during the prodromal stages of DLB with changes paralleling symptomatic progression. These data may inform clinical practice and trials planning to use FDG-PET for biologic staging, monitoring disease progression, and potentially assessing treatment response.
路易体连续体纵向FDG-PET代谢变化
尽管18f -氟脱氧葡萄糖正电子发射断层扫描(FDG-PET)是一种公认的路易体痴呆(DLB)脑代谢的横截面生物标志物,但FDG-PET的纵向变化尚未被表征。目的研究纵向FDG-PET在前驱DLB和DLB中的应用,包括尸检数据的子样本,并报告DLB假设临床试验的估计样本量。设计、环境和参与者:纵向病例对照研究,平均(SD)随访3.8(2.3)年。在2007年至2022年期间,在转诊中心和人群中连续招募病例。包括可能患有DLB或轻度认知障碍伴路易体(MCI-LB)的患者。无认知障碍的个体从年龄和性别平衡的人群队列中纳入进行比较。所有参与者至少完成1次随访评估。暴露于MCI-LB和DLB患者。FDG-PET的变化率以标准化摄取值比(SUVr)进行评估。临床进展用临床痴呆评分盒(CDR-SB)评分进行评估。结果共纳入35例疑似DLB患者、37例MCI-LB患者和100例无认知障碍患者。DLB组和MCI-LB组的平均(SD)年龄(n = 72)为69.6(8.2)岁;男性66例(92%),女性6例(8%)。随访时,18名MCI-LB患者(49%)进展为可能的DLB。与没有认知障碍的参与者相比,MCI-LB患者在后扣带、枕叶、顶叶、颞叶和外侧额叶皮层的FDG-SUVr下降更快。与没有认知障碍的参与者相比,DLB患者的相同区域显示出更大的代谢下降,其中增加了前-中扣带皮层、岛叶皮层和内侧额眶皮质。FDG-PET在这些大脑区域的变化率被合并成一个兴趣区域(ROI),标记为纵向FDG-PET LB - meta-ROI。meta-ROI中FDG-SUVr的变化率与CDR-SB的变化率相关,并报道了DLB潜在临床试验的样本量估计。这些发现在神经病理证实的亚样本中得到证实(n = 20)。结论和相关性本研究发现,脑代谢降低在DLB的前驱阶段开始演变,其变化与症状进展平行。这些数据可以为临床实践和试验计划使用FDG-PET进行生物分期、监测疾病进展和潜在评估治疗反应提供信息。
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来源期刊
JAMA neurology
JAMA neurology CLINICAL NEUROLOGY-
CiteScore
41.90
自引率
1.70%
发文量
250
期刊介绍: JAMA Neurology is an international peer-reviewed journal for physicians caring for people with neurologic disorders and those interested in the structure and function of the normal and diseased nervous system. The Archives of Neurology & Psychiatry began publication in 1919 and, in 1959, became 2 separate journals: Archives of Neurology and Archives of General Psychiatry. In 2013, their names changed to JAMA Neurology and JAMA Psychiatry, respectively. JAMA Neurology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.
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