Ferreira Daniel, Przybelski Scott A, Lesnick Timothy G, Diaz-Galvan Patricia, Schwarz Christopher G, Murray Melissa M, Dickson Dennis W, Nguyen Aivi, Reichard Ross R, Senjem Matthew L, Gunter Jeffrey L, Jack Clifford R, Min Paul H, Jain Manoj K, Miyagawa Toji, Forsberg Leah K, Fields Julie A, Savica Rodolfo, Graff-Radford Jonathan, Ramanan Vijay K, Jones David T, Botha Hugo, St Louis Erik K, Knopman David S, Graff-Radford Neill R, Day Gregory S, Ferman Tanis J, Kremers Walter K, Petersen Ronald C, Boeve Bradley F, Lowe Val J, Kantarci Kejal
Division of Clinical Geriatrics, Center for Alzheimer's Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.
Department of Radiology, Mayo Clinic, Rochester, Minnesota.
JAMA Neurol. 2025 Mar 1;82(3):285-294. doi: 10.1001/jamaneurol.2024.4643.
Although 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.
To 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 PARTICIPANTS: Longitudinal 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.
Patients with MCI-LB and DLB.
Rate 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.
Thirty-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).
This 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.
尽管18F-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）是路易体痴呆（DLB）中一种成熟的脑代谢横断面生物标志物，但FDG-PET的纵向变化尚未得到描述。
研究前驱期DLB和DLB患者的纵向FDG-PET情况，包括有尸检数据的子样本，并报告DLB一项假设性临床试验的估计样本量。
设计、设置和参与者：纵向病例对照研究，平均（标准差）随访3.8（2.3）年。2007年至2022年期间，在一个转诊中心和普通人群中连续招募病例。纳入可能患有DLB或路易体轻度认知障碍（MCI-LB）的患者。从年龄和性别均衡的基于人群的队列中纳入无认知障碍的个体进行比较。所有参与者按设计完成了至少1次随访评估。
MCI-LB和DLB患者。
FDG-PET的变化率以标准化摄取值比率（SUVr）进行评估。临床进展用临床痴呆评定量表总和（CDR-SB）评分进行评估。
纳入35例可能患有DLB的患者、37例MCI-LB患者和100例无认知障碍的个体。DLB组和MCI-LB组合并（n = 72）的平均（标准差）年龄为69.6（8.2）岁；66例患者（92%）为男性，6例（8%）为女性。随访时，18例（49%）MCI-LB患者进展为可能患有DLB。与无认知障碍的参与者相比，MCI-LB患者在后扣带回、枕叶、顶叶、颞叶和外侧额叶皮质的FDG-SUVr下降更快。与无认知障碍的参与者相比，DLB患者在相同区域显示出更大的代谢下降，此外还有前中部扣带回、岛叶和内侧额叶眶皮质。这些脑区FDG-PET的变化率合并为一个感兴趣区域（ROI），标记为纵向FDG-PET LB元ROI。元ROI中FDG-SUVr的变化率与CDR-SB的变化率相关，并报告了DLB潜在临床试验的样本量估计。在有神经病理学证实的子样本（n = 20）中证实了研究结果。
本研究发现，脑代谢减退在DLB的前驱期就开始演变，其变化与症状进展平行。这些数据可能为临床实践和试验规划提供信息，以便使用FDG-PET进行生物学分期、监测疾病进展以及潜在地评估治疗反应。
