Kang Sungwoo, Jeon Seun, Kim Yeoju, Jeon Su-Hee, Choi Minsun, Lee Young-Gun, Ye Byoung Seok
Department of Neurology, Hanyang Seoul Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea.
Metabolism-Dementia Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Alzheimers Dement. 2025 Nov;21(11):e70920. doi: 10.1002/alz.70920.
The clinical implications of brain hypermetabolism remain unexplored in Lewy body disease (LBD) co-pathology in Alzheimer's disease (AD).
We investigated cognition, F-fluorodeoxyglucose positron emission tomography (PET), and cerebrospinal fluid tau phosphorylated at threonine 181 (pTau)/Aβ plus α-synuclein seeding amplification assays (SAA) in controls, 217 SAA-negative AD (AD), and 124 SAA-positive AD (AD). Brain metabolism was assessed using subject residual profile (SRP) and standardized uptake value ratio (SUVR).
Compared to AD, AD showed putamen SRP hypermetabolism and middle occipital gyrus (MOG) SUVR hypometabolism. SAA positivity correlated with putamen SRP hypermetabolism independently of pTau/amyloid beta 42 (Aβ). Its interaction with pTau/Aβ influenced MOG SUVR, showing increased MOG SUVR with higher pTau/Aβ in AD. Putamen SRP hypermetabolism predicted faster cognitive decline and greater variability in both groups. MOG SUVR hypometabolism correlated with them only in AD. Adding putamen SRP hypermetabolism to models, including SAA positivity and AD signature hypometabolism, improved the prediction of cognitive decline/variability, whereas MOG SUVR did not.
Putaminal hypermetabolism may serve as a robust metabolic marker of LBD co-pathology in AD.
LB co-pathology in AD alters regional brain metabolism. SRP analyses capture putaminal hypermetabolism for SAA positivity. SUVR analyses emphasize occipital hypometabolism for SAA positivity. Occipital metabolism correlates positively with AD severity in mixed AD-LB. Putaminal, not occipital, metabolism predicts cognitive change over AD-related metabolism and SAA.
脑代谢亢进在阿尔茨海默病（AD）合并路易体病（LBD）共病中的临床意义尚未得到探索。
我们在对照组、217例淀粉样蛋白种子扩增检测（SAA）阴性的AD患者（AD）和124例SAA阳性的AD患者（AD）中，研究了认知、氟代脱氧葡萄糖正电子发射断层扫描（PET）以及脑脊液中苏氨酸181磷酸化的tau蛋白（pTau）/淀粉样β蛋白（Aβ）加α-突触核蛋白种子扩增检测（SAA）。使用受试者残差轮廓（SRP）和标准化摄取值比率（SUVR）评估脑代谢。
与AD相比，AD患者表现出壳核SRP代谢亢进和枕中回（MOG）SUVR代谢减退。SAA阳性与壳核SRP代谢亢进独立相关，与pTau/淀粉样β蛋白42（Aβ）无关。它与pTau/Aβ的相互作用影响MOG SUVR，在AD患者中，随着pTau/Aβ升高，MOG SUVR增加。壳核SRP代谢亢进预示着两组患者认知功能下降更快且变异性更大。MOG SUVR代谢减退仅在AD患者中与认知功能下降和变异性相关。将壳核SRP代谢亢进纳入包括SAA阳性和AD特征性代谢减退的模型中，可改善对认知功能下降/变异性的预测，而MOG SUVR则不然。
壳核代谢亢进可能是AD合并LBD共病的一个有力代谢标志物。
AD合并LBD共病会改变局部脑代谢。SRP分析捕捉到SAA阳性时壳核代谢亢进。SUVR分析强调SAA阳性时枕叶代谢减退。在AD-LB混合患者中，枕叶代谢与AD严重程度呈正相关。壳核而非枕叶代谢可预测AD相关代谢和SAA患者的认知变化。
