Vascular burden and APOE ε4 are associated with white matter microstructural decline in cognitively normal older adults
Vascular burden and APOE ε4 are associated with white matter microstructural decline in cognitively normal older adults
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DOI：
10.1016/j.neuroimage.2018.12.009
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发表时间：
2019-03-01
期刊：
影响因子：
5.7
通讯作者：
Resnick, Susan M.
中科院分区：
文献类型：
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作者：
Williams, Owen A.;An, Yang;Resnick, Susan M.
白色物质的显微结构可以用扩散张量成像（DTI）测量。虽然年龄的增加是一个预测白色物质（WM）的微观结构的变化，其他可能的修饰符，如心血管危险因素，载脂蛋白E β 4等位基因状态和生物sex.We的角色还没有澄清调查665认知正常的参与者从巴尔的摩纵向研究老化（年龄50-95，56.7%的女性），共1384 DTI扫描。WM微观结构通过分数各向异性（FA）和平均扩散率（MD）进行评估。血管负荷评分定义为五个风险因素（高血压、肥胖、胆固醇升高、糖尿病和吸烟状况）的总和。线性混合效应模型评估了基线血管负荷与基线以及平均随访3.6年的FA和MD变化率的相关性，同时控制了年龄、种族和扫描仪类型。我们还比较了载脂蛋白E β 4携带者与非携带者以及男性与女性的DTI轨迹。在基线时，在许多WM结构中，包括联合、连合和投射纤维，较高的血管负荷与较低的FA和较高的MD相关。较高的基线血管负荷也与扣带回海马部分和穹窿（穹隆）/终纹和胼胝体压部的FA纵向下降较大相关，并且与胼胝体压部的MD增加较大相关。APOE β 4携带者在基线DTI指标上与非携带者没有差异，但在胼胝体的前额叶和压部FA下降更大。在基线时，男性在多个WM区域具有较高的FA和较低的MD，但在胼胝体前部的MD显示出更大的增加。女性表现出更大的减少，随着时间的推移，在FA的扣带回的一部分，相比于男性，我们的研究结果表明，可修改的血管危险因素（1）有一个负面的影响，白色物质的微观结构和（2）与更快的微观结构恶化的颞WM地区和胼胝体压部在认知正常的成年人。减少衰老过程中的血管负荷可以改变WM恶化的速度，并可以减少与年龄相关的认知下降和损伤。
White matter microstructure can be measured with diffusion tensor imaging (DTI). While increasing age is a predictor of white matter (WM) microstructure changes, roles of other possible modifiers, such as cardiovascular risk factors, APOE epsilon 4 allele status and biological sex have not been clarified.We investigated 665 cognitively normal participants from the Baltimore Longitudinal Study of Aging (age 50-95, 56.7% female) with a total of 1384 DTI scans. WM microstructure was assessed by fractional anisotropy (FA) and mean diffusivity (MD). A vascular burden score was defined as the sum of five risk factors (hypertension, obesity, elevated cholesterol, diabetes and smoking status). Linear mixed effects models assessed the association of baseline vascular burden on baseline and on rates of change of FA and MD over a mean follow-up of 3.6 years, while controlling for age, race, and scanner type. We also compared DTI trajectories in APOE epsilon 4 carriers vs. non-carriers and men vs. women.At baseline, higher vascular burden was associated with lower FA and higher MD in many WM structures including association, commissural, and projection fibers. Higher baseline vascular burden was also associated with greater longitudinal decline in FA in the hippocampal part of the cingulum and the fornix (crus)/stria terminalis and splenium of the corpus callosum, and with greater increases in MD in the splenium of the corpus callosum. APOE epsilon 4 carriers did not differ from non-carriers in baseline DTI metrics but had greater decline in FA in the genu and splenium of the corpus callosum. Men had higher FA and lower MD in multiple WM regions at baseline but showed greater increase in MD in the genu of the corpus callosum. Women showed greater decreases over time in FA in the gyrus part of the cingulum, compared to men.Our findings show that modifiable vascular risk factors (1) have a negative impact on white matter microstructure and (2) are associated with faster microstructural deterioration of temporal WM regions and the splenium of the corpus callosum in cognitively normal adults. Reducing vascular burden in aging could modify the rate of WM deterioration and could decrease age-related cognitive decline and impairment.