Wei Min, Wang Luyao, Yu Xianfeng, Hu Wenjing, Wang Min, Zhang Qi, Guo Tengfei, Zhong Jiayi, Li Chenyang, Jiang Jiehui, Han Ying
Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Institute of Biomedical Engineering, School of Life Sciences, Shanghai University, Shanghai, China.
CNS Neurosci Ther. 2025 May;31(5):e70264. doi: 10.1111/cns.70264.
Glucose metabolism and plasma biomarkers have emerged as important early markers in Alzheimer's disease. Different subtypes (single memory domain, multidomain) of subjective cognitive decline (SCD) may represent distinct stages of disease progression, but the differences in glucose metabolism remain unclear. This study focused on exploring the differences in glucose metabolism between different SCD subtypes and the correlation with plasma biomarkers based on F-FDG PET.
In this study, thirty-three normal controls (NCs), thirty-five individuals with single memory domain SCD (sd-SCD), thirty-nine individuals with multidomain SCD (md-SCD), and twenty-one cognitively impaired (CI) individuals were involved. We investigated the standardized uptake value ratio (SUVR) and voxel differences between the sd-SCD and md-SCD groups followed by FDR and GRF corrections, with an average follow-up time of 44.98 ± 16.49 months. Correlation analyses were employed to assess relationships between FDG-PET SUVR and neuropsychological scales as well as plasma biomarkers. Finally, Kaplan-Meier survival analysis was used to investigate the risk of cognitive decline conversion among SCD subgroups.
After controlling for the effects of covariates, the following brain regions showed voxel differences and lower SUVR in md-SCD groups, including right anterior cingulate and paracingulate gyri (ACG.R, p = 0.003), left anterior cingulate and paracingulate gyri (ACG.L, p = 0.003), right middle temporal gyrus (MTG.R, p = 0.004), and right inferior temporal gyrus (ITG.R, p = 0.001), compared to the sd-SCD group. SUVR of ACG.R was correlated with plasma Aβ42/40 (r = 0.435, p = 0.006) and AVLT-N7 score (r = 0.347, p = 0.031) in the md-SCD group while none of the correlations existed in the sd-SCD group. SUVR of MTG.R was also correlated with the AVLT-N7 score (r = 0.246, p = 0.035) across SCD individuals. The SCD individuals with positive plasma Aβ42/40, p-tau181, and glucose metabolism in above four regions, or those in the md-SCD group showed an elevated risk of cognitive conversion in comparison to the controls.
Differences in glucose metabolism could be observed between the md-SCD and sd-SCD groups. SCD participants in the md-SCD group, or those with positive biomarkers, might represent a higher risk of cognitive decline conversion.
葡萄糖代谢和血浆生物标志物已成为阿尔茨海默病重要的早期标志物。主观认知下降（SCD）的不同亚型（单一记忆领域、多领域）可能代表疾病进展的不同阶段，但葡萄糖代谢的差异尚不清楚。本研究基于F-FDG PET，重点探讨不同SCD亚型之间葡萄糖代谢的差异以及与血浆生物标志物的相关性。
本研究纳入了33名正常对照（NC）、35名单一记忆领域SCD（sd-SCD）个体、39名多领域SCD（md-SCD）个体和21名认知障碍（CI）个体。我们研究了sd-SCD组和md-SCD组之间的标准化摄取值比率（SUVR）和体素差异，随后进行FDR和GRF校正，平均随访时间为44.98±16.49个月。采用相关性分析评估FDG-PET SUVR与神经心理量表以及血浆生物标志物之间的关系。最后，采用Kaplan-Meier生存分析研究SCD亚组中认知下降转化的风险。
在控制协变量的影响后，与sd-SCD组相比，md-SCD组的以下脑区显示体素差异且SUVR较低，包括右侧前扣带回和旁扣带回（ACG.R，p = 0.003）、左侧前扣带回和旁扣带回（ACG.L，p = 0.003）、右侧颞中回（MTG.R，p = 0.004）和右侧颞下回（ITG.R，p = 0.001）。md-SCD组中ACG.R的SUVR与血浆Aβ42/40（r = 0.435，p = 0.006）和AVLT-N7评分（r = 0.347，p = 0.031）相关，而sd-SCD组中不存在这些相关性。MTG.R的SUVR在所有SCD个体中也与AVLT-N7评分相关（r = 0.246，p = 0.035）。与对照组相比，血浆Aβ42/40、p-tau181呈阳性且上述四个区域存在葡萄糖代谢的SCD个体，或md-SCD组个体发生认知转化的风险升高。
md-SCD组和sd-SCD组之间可观察到葡萄糖代谢的差异。md-SCD组的SCD参与者或生物标志物呈阳性的参与者可能代表认知下降转化的风险更高。
