Pupillary dilation responses as a midlife indicator of risk for Alzheimer's disease: association with Alzheimer's disease polygenic risk
Pupillary dilation responses as a midlife indicator of risk for Alzheimer's disease: association with Alzheimer's disease polygenic risk
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DOI：
10.1016/j.neurobiolaging.2019.09.001
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发表时间：
2019-11-01
影响因子：
4.2
通讯作者：
Franz, Carol E.
中科院分区：
文献类型：
--
作者：
Kremen, William S.;Panizzon, Matthew S.;Franz, Carol E.
蓝斑（LC）tau积累开始较早。靶向LC（dys）功能可能会改善阿尔茨海默病（AD）风险的早期识别。认知任务期间的瞳孔反应由LC和指数认知努力驱动。尽管有相同的任务表现，轻度认知障碍的成年人有更大的瞳孔扩张/努力在数字跨度比认知正常（CN）的个人。我们假设AD多基因风险评分（AD-PRS）与中年CN成人的瞳孔反应相关。在1119名56-66岁的男性中，数字广度任务的瞳孔反应是可遗传的（h（2）= 0.30-0.36）。在CN子集中-所有具有可比跨度容量的患者（n = 539）-在高（9位数）认知负荷条件下，较高的AD-PRS与较大的瞳孔扩张/努力相关（对于AD-PRS分布的上四分位数与下四分位数，Cohen d = 0.36）。控制APOE基因型后，结果保持不变。结果支持瞳孔反应--以及由此推断的LC功能障碍--作为早期轻度认知障碍/AD风险的遗传介导的生物标志物。与其他生物标志物相结合，任务诱发的瞳孔反应可以提供额外的信息，甚至在认知能力下降之前，就可以对有遗传风险的个体进行早期筛查。(C)2019爱思唯尔公司All rights reserved.
Locus coeruleus (LC) tau accumulation begins early. Targeting LC (dys)function might improve early identification for Alzheimer's disease (AD) risk. Pupillary responses during cognitive tasks are driven by the LC and index cognitive effort. Despite equivalent task performance, adults with mild cognitive impairment have greater pupil dilation/effort during digit span than cognitively normal (CN) individuals. We hypothesized that AD polygenic risk scores (AD-PRSs) would be associated with pupillary responses in middle-aged CN adults. Pupillary responses during digit span tasks were heritable (h(2) = 0.30-0.36) in 1119 men aged 56-66 years. In a CN subset-all with comparable span capacities (n = 539)-higher AD-PRSs were associated with greater pupil dilation/effort in a high (9-digit) cognitive load condition (Cohen's d = 0.36 for upper vs. lower quartile of AD-PRS distribution). Results held up after controlling for APOE genotype. Results support pupillary response-and by inference, LC dysfunction-as a genetically mediated biomarker of early mild cognitive impairment/AD risk. In combination with other biomarkers, task-evoked pupillary responses may provide additional information for early screening of genetically at-risk individuals even before cognitive declines. (C) 2019 Elsevier Inc. All rights reserved.