Burzynska Agnieszka Z, Anderson Charles, Arciniegas David B, Calhoun Vince, Choi In-Young, Mendez Colmenares Andrea, Kramer Arthur F, Li Kaigang, Lee Jongho, Lee Phil, Thomas Michael L
The BRAiN lab, Department of Human Development and Family Studies/Molecular, Cellular and Integrative Neurosciences, Colorado State University, Fort Collins, CO, USA.
Department of Computer Science, Colorado State University, Fort Collins, CO, USA.
Cereb Circ Cogn Behav. 2024 Jan 12;6:100203. doi: 10.1016/j.cccb.2024.100203. eCollection 2024.
As the emerging treatments that target grey matter pathology in Alzheimer's Disease have limited effectiveness, there is a critical need to identify new neural targets for treatments. White matter's (WM) metabolic vulnerability makes it a promising candidate for new interventions. This study examined the age and sex differences in estimates of axonal content, as well the associations of with highly prevalent modifiable health risk factors such as metabolic syndrome and adiposity. We estimated intra-axonal volume fraction (ICVF) using the Neurite Orientation Dispersion and Density Imaging (NODDI) in a sample of 89 cognitively and neurologically healthy adults (20-79 years). We showed that ICVF correlated positively with age and estimates of myelin content. The ICVF was also lower in women than men, across all ages, which difference was accounted for by intracranial volume. Finally, we found no association of metabolic risk or adiposity scores with the current estimates of ICVF. In addition, the previously observed adiposity-myelin associations (Burzynska et al., 2023) were independent of ICVF. Although our findings confirm the vulnerability of axons to aging, they suggest that metabolic dysfunction may selectively affect myelin content, at least in cognitively and neurologically healthy adults with low metabolic risk, and when using the specific MRI techniques. Future studies need to revisit our findings using larger samples and different MRI approaches, and identify modifiable factors that accelerate axonal deterioration as well as mechanisms linking peripheral metabolism with the health of myelin.
由于针对阿尔茨海默病灰质病理的新兴治疗方法效果有限，因此迫切需要确定新的治疗神经靶点。白质（WM）的代谢易损性使其成为新干预措施的一个有前景的候选靶点。本研究调查了轴突含量估计值的年龄和性别差异，以及与代谢综合征和肥胖等高度普遍的可改变健康风险因素的关联。我们使用神经突方向离散度和密度成像（NODDI）对89名认知和神经健康的成年人（20 - 79岁）进行了轴突内体积分数（ICVF）的估计。我们发现ICVF与年龄和髓磷脂含量估计值呈正相关。在所有年龄段中，女性的ICVF也低于男性，这种差异由颅内体积所解释。最后，我们发现代谢风险或肥胖评分与当前的ICVF估计值之间没有关联。此外，先前观察到的肥胖与髓磷脂的关联（Burzynska等人，2023年）与ICVF无关。尽管我们的研究结果证实了轴突对衰老的易损性，但它们表明代谢功能障碍可能选择性地影响髓磷脂含量，至少在代谢风险较低的认知和神经健康成年人中，以及使用特定MRI技术时是这样。未来的研究需要使用更大的样本和不同的MRI方法重新审视我们的发现，并确定加速轴突退化的可改变因素以及将外周代谢与髓磷脂健康联系起来的机制。
