McIntyre Clayton C, Lyday Robert G, Su Yixin, Nicklas Barbara, Simpson Sean L, Deep Gagan, Macauley Shannon L, Hugenschmidt Christina E
Neuroscience Graduate Program, Wake Forest Graduate School of Arts and Sciences, Winston-Salem, NC, USA.
Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
bioRxiv. 2025 Jan 6:2024.11.26.625552. doi: 10.1101/2024.11.26.625552.
Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral and neuronal insulin resistance (IR) relate to executive function and functional brain network topology.
Older adults (n=71) with obesity but without type 2 diabetes were included. Peripheral IR was quantified by HOMA2-IR. Neuronal IR was quantified according to a proposed neuron-derived exosome-based method (NDE-IR). An executive function composite score, summed scores to the Auditory Verbal Learning Test (AVLT) trials 1-5, and functional brain networks generated from resting-state functional magnetic resonance imaging were outcomes in analyses. We used general linear models and a novel regression framework for brain network analysis to identify relationships between IR measures and brain-related outcomes.
HOMA2-IR, but not NDE-IR, was negatively associated with executive function. Neither IR measure was associated with AVLT score. Peripheral IR was also related to hippocampal network topology in participants who had undergone functional neuroimaging. Neither peripheral nor neuronal IR were significantly related to network topology of the central executive network.
Cognitive and functional imaging effects were observed from HOMA2-IR, but not NDE-IR. The hippocampus may be particularly vulnerable to effects of peripheral IR.
使用来自肥胖老年人样本的横断面数据来确定外周和神经元胰岛素抵抗（IR）与执行功能和功能性脑网络拓扑结构之间的关系。
纳入了患有肥胖症但无2型糖尿病的老年人（n = 71）。通过HOMA2-IR对外周IR进行量化。根据一种基于神经元衍生外泌体的方法（NDE-IR）对神经元IR进行量化。在分析中，执行功能综合评分、听觉词语学习测试（AVLT）第1 - 5次试验的总分以及由静息态功能磁共振成像生成的功能性脑网络为研究结果。我们使用一般线性模型和一种用于脑网络分析的新型回归框架来确定IR测量值与脑相关结果之间的关系。
HOMA2-IR与执行功能呈负相关，而NDE-IR与执行功能无此相关性。两种IR测量值均与AVLT评分无关。外周IR也与接受功能神经成像的参与者的海马网络拓扑结构有关。外周和神经元IR均与中央执行网络的网络拓扑结构无显著相关性。
观察到HOMA2-IR对认知和功能成像有影响，而NDE-IR则无此影响。海马体可能对外周IR的影响尤为敏感。
