Seok Ji-Woo, Kim Kahye, Hwang Soonjo, Lee Kun Ho, Kim Jaeuk U
Digital Health Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
Department of Psychiatry, University of Nebraska Medical Center, Omaha, NE, United States.
Front Aging Neurosci. 2025 Aug 22;17:1592341. doi: 10.3389/fnagi.2025.1592341. eCollection 2025.
The role of triglycerides in Alzheimer's disease dementia (ADD) progression remains unclear. This study aimed to investigate how triglyceride levels influence the relationship between amyloid-beta (Aβ) deposition, hippocampal atrophy, and cognitive decline in individuals with mild cognitive impairment (MCI) and early-stage ADD.
A total 188 older adults (170 with MCI, 18 with early ADD) from the Gwangju Alzheimer's Disease and Related cohort underwent amyloid PET and structural magnetic resonance imaging. Cognitive decline was assessed using the Korean version of the Mini-Mental State Examination (K-MMSE). A moderated mediation model (PROCESS model 7 with 10,000 bootstrap samples) was applied to examine whether hippocampal atrophy mediated the effect of Aβ on cognitive decline and whether this effect varied by triglyceride levels.
The indirect effect of Aβ deposition on cognitive decline through hippocampal atrophy was significant (bootstrap 95% CI: -0.39 to -0.08), while the direct effect was not. This suggests that hippocampal atrophy plays a substantial mediating role in the pathway from Aβ burden to cognitive decline, although the indirect path accounted for approximately 49% of the total effect, indicating the possibility of other unexplored mechanisms. Furthermore, moderated mediation analysis revealed that triglyceride levels significantly moderated the effect of Aβ deposition on hippocampal volume ( < 0.05), with higher triglyceride levels amplifying the negative impact of Aβ deposition on hippocampal atrophy.
These findings highlight hippocampal atrophy as a key pathway linking Aβ burden to cognitive impairment. Moreover, higher triglyceride levels may exacerbate Aβ-related neurodegeneration in individuals with MCI and early-stage ADD. Metabolic risk factors, such as triglycerides, may play an important role in strategies to prevent or delay cognitive decline in older adults with MCI and early ADD.
甘油三酯在阿尔茨海默病性痴呆（ADD）进展中的作用仍不明确。本研究旨在探讨甘油三酯水平如何影响轻度认知障碍（MCI）和早期ADD患者中β淀粉样蛋白（Aβ）沉积、海马萎缩与认知衰退之间的关系。
来自光州阿尔茨海默病及相关队列的188名老年人（170名MCI患者，18名早期ADD患者）接受了淀粉样蛋白PET和结构磁共振成像检查。使用韩国版简易精神状态检查表（K-MMSE）评估认知衰退情况。应用调节中介模型（PROCESS模型7，10000次自抽样）来检验海马萎缩是否介导了Aβ对认知衰退的影响，以及这种影响是否因甘油三酯水平而异。
Aβ沉积通过海马萎缩对认知衰退的间接效应显著（自抽样95%CI：-0.39至-0.08），而直接效应不显著。这表明海马萎缩在从Aβ负荷到认知衰退的通路中起重要中介作用，尽管间接路径约占总效应的49%，这表明可能存在其他未被探索的机制。此外，调节中介分析显示，甘油三酯水平显著调节了Aβ沉积对海马体积的影响（<0.05），较高的甘油三酯水平放大了Aβ沉积对海马萎缩的负面影响。
这些发现突出了海马萎缩是将Aβ负荷与认知障碍联系起来的关键通路。此外，较高的甘油三酯水平可能会加剧MCI和早期ADD患者中与Aβ相关的神经变性。甘油三酯等代谢危险因素可能在预防或延缓MCI和早期ADD老年人认知衰退的策略中发挥重要作用。
