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.
Sci Rep. 2025 Jul 2;15(1):22612. doi: 10.1038/s41598-025-06038-1.
Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral insulin resistance (PIR) and neuronal insulin signaling abnormalities (NISAs) relate to executive function and functional brain network topology. Older adults (n = 71) with obesity but without type 2 diabetes were included. PIR was quantified by HOMA2-IR. NISAs were quantified according to an established neuron-derived small-extracellular-vesicle-based metric, R. 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 data were outcomes in analyses. We used general linear models and a novel regression framework for brain network analysis to identify relationships between insulin-related biomarkers and brain-related outcomes. HOMA2-IR, but not R, was negatively associated with executive function. Neither measure was associated with AVLT score. HOMA2-IR was also related to hippocampal network topology in participants who had undergone functional neuroimaging. Neither HOMA2-IR nor R were significantly related to network topology of the central executive network. This study provides further evidence that PIR is associated with aging brain function. NISAs were not found to be related to PIR, cognition, or functional brain network topology.
来自一组肥胖老年人的横断面数据被用于确定外周胰岛素抵抗（PIR）和神经元胰岛素信号异常（NISAs）与执行功能及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）。PIR通过HOMA2-IR进行量化。NISAs根据一种既定的基于神经元衍生的小细胞外囊泡的指标R进行量化。执行功能综合评分、听觉词语学习测试（AVLT）第1 - 5次试验的总分以及从静息态功能磁共振成像数据生成的功能性脑网络是分析中的结果。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胰岛素相关生物标志物与脑相关结果之间的关系。HOMA2-IR而非R与执行功能呈负相关。两种测量方法均与AVLT评分无关。HOMA2-IR还与接受过功能神经成像的参与者的海马网络拓扑结构有关。HOMA2-IR和R均与中央执行网络的网络拓扑结构无显著关系。这项研究提供了进一步的证据表明PIR与衰老脑功能相关。未发现NISAs与PIR、认知或功能性脑网络拓扑结构有关。
