Age-related differences in white matter integrity and cognitive function are related to APOE status.
Age-related differences in white matter integrity and cognitive function are related to APOE status.
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DOI：
10.1016/j.neuroimage.2010.08.052
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发表时间：
2011-01-15
期刊：
影响因子：
5.7
通讯作者：
Glisky EL
中科院分区：
文献类型：
--
作者：
Ryan L;Walther K;Bendlin BB;Lue LF;Walker DG;Glisky EL
虽然现在有大量的文献可用于通过弥散MRI测量的白色物质完整性的年龄相关差异，但对老年人的弥散和认知功能之间的关系知之甚少。关于这些关系是否受载脂蛋白（APOE）ε4等位基因的影响，我们知道的更少，尽管越来越多的证据表明ε4增加了老年人的认知障碍。本研究的目的是在一组居住在社区的认知正常的老年人检查这些关系。数据来自126名个体（年龄52-92岁）的样本，其中包括32名ε4杂合子，6名ε4纯合子和88名非携带者。从6个脑区--额叶白色物质、侧顶叶白色物质、半卵圆中心、胼胝体压部和颞干白色物质--获得两种弥散测量值，表观弥散系数（ADC）和各向异性分数（FA），并用于预测执行功能和记忆功能两个领域的认知功能综合评分。结果表明，随着年龄的增长，ADC和FA在所有六个脑区的不同，这些差异显着更大的ε4携带者相比，非携带者。重要的是，在控制年龄后，弥散测量以特定区域的方式预测认知功能，这也受到ε4状态的影响。无论APOE状态如何，额叶ADC和FA独立预测所有参与者的执行功能评分，而颞叶ADC还预测ε4携带者的执行功能，但非携带者则不然。所有参与者的记忆分数都是由颞叶ADC预测的，而不是由额叶弥散预测的，与非携带者相比，ε4携带者的这种关系明显更强。总的来说，年龄和颞叶ADC占ε4携带者组记忆评分方差的53%。这些结果进一步证明，APOE ε4对老年人年龄相关认知功能的轨迹具有显著影响。讨论了可能的机制，可以解释ε4，扩散和认知功能之间的关联，包括ε4对神经修复，氧化应激和髓鞘产生的少突胶质细胞的健康的影响。
While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ε4 allele, despite growing evidence that ε4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52–92) that included 32 ε4 heterozygotes, 6 ε4 homozygotes, and 88 non-carriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions – frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter – and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ε4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ε4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ε4 carriers, but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ε4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ε4 carrier group. The results provide further evidence that APOE ε4 has a significant impact on the trajectory of age-related cognitive functioning in older adults. Possible mechanisms are discussed that could account for the associations between ε4, diffusion, and cognitive function, including the influence of ε4 on neural repair, oxidative stress, and the health of myelin-producing oligodendroglia.
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