肥胖与阿尔茨海默病痴呆生物标志物阴性的认知正常个体中的白质神经炎症相关水肿
Obesity and White Matter Neuroinflammation Related Edema in Alzheimer's Disease Dementia Biomarker Negative Cognitively Normal Individuals.
作者信息
Ly Maria, Raji Cyrus A, Yu Gary Z, Wang Qing, Wang Yong, Schindler Suzanne E, An Hongyu, Samara Amjad, Eisenstein Sarah A, Hershey Tamara, Smith Gordon, Klein Samuel, Liu Jingxia, Xiong Chengjie, Ances Beau M, Morris John C, Benzinger Tammie L S
机构信息
University of Pittsburgh Medical Scientist Training Program, Pittsburgh, PA, USA.
Mallinckrodt Institute of Radiology, Division of Neuroradiology, Washington University in St. Louis, St. Louis, MO, USA.
出版信息
J Alzheimers Dis. 2021;79(4):1801-1811. doi: 10.3233/JAD-201242.
BACKGROUND
Obesity is related to quantitative neuroimaging abnormalities including reduced gray matter volumes and impaired white matter microstructural integrity, although the underlying mechanisms are not well understood.
OBJECTIVE
We assessed influence of obesity on neuroinflammation imaging that may mediate brain morphometric changes. Establishing the role of neuroinflammation in obesity will enhance understanding of this modifiable disorder as a risk factor for Alzheimer's disease (AD) dementia.
METHODS
We analyzed brain MRIs from 104 cognitively normal participants (CDR = 0) and biomarker negativity for CSF amyloid or tau. We classified body mass index (BMI) as normal (BMI <25, N = 62) or overweight and obese (BMI ≥25, N = 42). Blood pressure was measured. BMI and blood pressure classifications were related to neuroinflammation imaging (NII) derived edema fraction in 17 white matter tracts. This metric was also correlated to hippocampal volumes and CSF biomarkers of inflammation and neurodegeneration: YKL-40, SNAP25, VILIP, tau, and NFL.
RESULTS
Participants with BMI <25 had lower NII-derived edema fraction, with protective effects of normal blood pressure. Statistically significant white matter tracts included the internal capsule, external capsule, and corona radiata, FDR correc-ted for multiple comparisons to alpha = 0.05. Higher NII-derived edema fractions in the internal capsule, corpus callosum, gyrus, and superior fronto-occipital fasciculus were related with smaller hippocampal volumes only in individuals with BMI ≥25. There were no statistically significant correlations between NII-derived edema fraction and CSF biomarkers.
CONCLUSION
We demonstrate statistically significant relationships between neuroinflammation, elevated BMI, and hippocampal volume, raising implications for neuroinflammation mechanisms of obesity-related brain dysfunction in cognitively normal elderly.
背景
肥胖与定量神经影像学异常有关，包括灰质体积减少和白质微结构完整性受损，但其潜在机制尚未完全明确。
目的
我们评估了肥胖对神经炎症成像的影响，神经炎症成像可能介导脑形态学变化。确定神经炎症在肥胖中的作用将有助于加深对这种可改变的疾病作为阿尔茨海默病（AD）痴呆风险因素的理解。
方法
我们分析了104名认知正常参与者（临床痴呆评定量表[CDR]=0）的脑部磁共振成像（MRI），以及脑脊液淀粉样蛋白或tau蛋白生物标志物阴性情况。我们将体重指数（BMI）分为正常（BMI<25，n=62）或超重及肥胖（BMI≥25，n=42）。测量血压。BMI和血压分类与17条白质束中神经炎症成像（NII）衍生的水肿分数相关。该指标还与海马体积以及炎症和神经退行性变的脑脊液生物标志物：YKL-40、突触体相关蛋白25（SNAP25）、视锥蛋白样蛋白（VILIP）、tau蛋白和神经丝轻链（NFL）相关。
结果
BMI<25的参与者NII衍生的水肿分数较低，正常血压具有保护作用。具有统计学意义的白质束包括内囊、外囊和放射冠，经错误发现率（FDR）校正用于多重比较，α=0.05。仅在BMI≥25的个体中，内囊、胼胝体、脑回和额枕上束中较高的NII衍生水肿分数与较小的海马体积相关。NII衍生的水肿分数与脑脊液生物标志物之间无统计学意义的相关性。
结论
我们证明了神经炎症、BMI升高和海马体积之间存在统计学意义的关系，这对认知正常老年人肥胖相关脑功能障碍的神经炎症机制具有启示意义。
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