It remains unclear whether the genetic risk for late‐onset Alzheimer disease (AD) is linked to premorbid individual differences in general cognitive ability and brain structure. The objective of the present study was to determine whether the genetic risk of late‐onset AD is related to premorbid individual differences in intelligence quotient (IQ) and characteristics of the cerebral white‐matter in children. The study sample included children of the Generation R Study from Rotterdam, The Netherlands. IQ was measured using a well‐validated Dutch nonverbal IQ test (n = 1908) at ages 5 to 9 years. White‐matter microstructure was assessed by measuring fractional anisotropy (FA) of white‐matter tracts using diffusion tensor imaging (DTI) (n = 919) at ages 9 to 12 years. Genetic risk was quantified using three biologically defined genetic risk scores (GRSs) hypothesized to be related to the pathophysiology of late‐onset AD: immune response, cholesterol/lipid metabolism and endocytosis. Higher genetic risk for late‐onset AD that included genes associated with immune responsivity had a negative influence on cognition and cerebral white‐matter microstructure. For each unit increase in the immune response GRS, IQ decreased by 0.259 SD (95% CI [−0.500, −0.017]). For each unit increase in the immune response GRS, global FA decreased by 0.373 SD (95% CI [−0.721, −0.026]). Neither cholesterol/lipid metabolism nor endocytosis GRSs were associated with IQ or cerebral white‐matter microstructure. Our findings suggest that elevated genetic risk for late‐onset AD may in part be manifest during childhood neurodevelopment through alterations in immune responsivity.

中文翻译：

---

儿童阿尔茨海默氏病的遗传风险：来自早期智商和脑白质微观结构的证据。

尚不清楚晚期阿尔茨海默病（AD）的遗传风险是否与总体认知能力和脑结构的病前个体差异有关。本研究的目的是确定迟发性AD的遗传风险是否与儿童的智商（IQ）和脑白质特征的病前个体差异有关。该研究样本包括来自荷兰鹿特丹的R代研究的孩子。使用经过充分验证的荷兰非语言智商测验（n = 1908）在5至9岁时测量智商。通过使用9到12岁的弥散张量成像（DTI）（n = 919）测量白色物质的分数各向异性（FA）来评估白色物质的微观结构。遗传风险使用三个生物学定义的遗传风险评分（GRS）进行量化，这些评分被认为与晚期AD的病理生理有关：免疫应答，胆固醇/脂质代谢和胞吞作用。晚期AD的较高遗传风险，包括与免疫反应相关的基因，对认知和脑白质微观结构有负面影响。免疫应答GRS每升高一个单位，智商就会降低0.259 SD（95％CI [-0.500，-0.017]）。免疫应答GRS每增加一个单位，总体FA就会降低0.373 SD（95％CI [-0.721，-0.026]）。胆固醇/脂质代谢或内吞GRS均与智商或脑白质微观结构无关。