UNC5C 等位基因可预测临床正常老年人群的认知能力下降和海马体萎缩。
An UNC5C Allele Predicts Cognitive Decline and Hippocampal Atrophy in Clinically Normal Older Adults.
机构信息
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA.
出版信息
J Alzheimers Dis. 2019;68(3):1161-1170. doi: 10.3233/JAD-180788.
BACKGROUND
The UNC5C rs3846455G allele has been linked to poor cognitive resilience against age-related neuropathologies, but this association remains to be replicated, and the allele's effect on hippocampal neurodegeneration needs to be examined.
OBJECTIVE
To further validate the association between rs3846455G and faster cognitive decline, especially among cognitively normal older adults, and to assess whether rs3846455G predicts accelerated hippocampal volume loss in older adults.
METHODS
We assessed participants in the Harvard Aging Brain Study (HABS), a longitudinal cohort study of older adults who were clinically normal at baseline. To avoid bias from population admixture, analyses were limited to participants of European descent with longitudinal neuroimaging data (n = 174). Linear mixed effect models were used to examine the effect of rs3846455G on longitudinal change of the Preclinical Alzheimer Cognitive Composite (PACC) and MRI-measured bilateral hippocampal volume, adjusting for baseline amyloid-β (Aβ) measured by the cortical Pittsburgh Compound B PET distributed volume ratio. We also tested whether hippocampal atrophy mediates the association between rs3846455G and greater PACC decline through a mediation analysis.
RESULTS
rs3846455G was associated with greater PACC decline (β= -0.087/year, 95% CI -0.169 to -0.005, p = 0.039) after controlling for baseline Aβ. Further, rs3846455G predicted accelerated hippocampal atrophy after controlling for baseline Aβ (β= -57.3 mm3/year, 95% CI -102.8 to -11.9, p = 0.014). The association between rs3846455G and greater PACC decline was partially mediated by accelerated hippocampal atrophy (mediated effect (relative scale) = -0.014, 95% CI -0.032 to -6.0×10-4, p = 0.039).
CONCLUSION
UNC5C rs3846455G predicts greater cognitive decline and accelerated hippocampal atrophy in clinically normal older adults.
背景
UNC5C rs3846455G 等位基因与年龄相关神经病理学的认知弹性差有关，但这一关联仍有待复制，该等位基因对海马体神经退行性变的影响需要进一步研究。
目的
进一步验证 rs3846455G 与认知能力下降速度加快之间的关联，特别是在认知正常的老年人中，并评估 rs3846455G 是否预测老年人海马体体积加速丢失。
方法
我们评估了哈佛衰老大脑研究（HABS）中的参与者，这是一项针对临床正常老年人的纵向队列研究。为避免人群混合造成的偏差，分析仅限于具有纵向神经影像学数据的欧洲血统参与者（n=174）。线性混合效应模型用于检验 rs3846455G 对临床前阿尔茨海默病认知综合指数（PACC）和 MRI 测量的双侧海马体体积的纵向变化的影响，调整基线时皮质 Pittsburgh 复合 B PET 分布体积比测量的淀粉样蛋白-β（Aβ）。我们还通过中介分析测试了海马体萎缩是否介导了 rs3846455G 与更大的 PACC 下降之间的关联。
结果
在控制基线 Aβ 后，rs3846455G 与 PACC 下降幅度更大相关（β=-0.087/年，95%置信区间-0.169 至-0.005，p=0.039）。此外，在控制基线 Aβ 后，rs3846455G 预测了海马体萎缩的加速（β=-57.3mm3/年，95%置信区间-102.8 至-11.9，p=0.014）。rs3846455G 与更大的 PACC 下降之间的关联部分通过加速的海马体萎缩来介导（中介效应（相对规模）=-0.014，95%置信区间-0.032 至-6.0×10-4，p=0.039）。
结论
UNC5C rs3846455G 预测了临床正常老年人中更大的认知能力下降和加速的海马体萎缩。
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