We aimed to determine the association of family history of dementia with structural brain measures and cognitive performance in childhood and mid-life adulthood. We studied 1,259 parents (mean age: 47.3 years, range 31.9–67.4) and 866 of their children (mean age [range] at brain MRI: 9.9 years [8.8–11.9], and for cognition: 13.5 years [12.6–15.8]) of the population-based Generation R Study. Parents filled in a questionnaire on family history, and both parents and children underwent cognitive assessment and neuroimaging. Of all participants, 109 parents (8.6%) reported a parental family history of dementia and 73 children (8.4%) had a grandparental history of dementia with mean age of dementia diagnosis in those affected 75 years (± 7.3). We observed no associations of dementia family history with cognitive ability in either parents or their children, except for worse Purdue pegboard in parents with a parental history of dementia, compared to those without (mean difference [95%CI]: -1.23 [-2.15; -0.31], test range: 21–52). In parents and children, neuroimaging measures did not differ significantly by family history. Results did not depend on age, sex, and APOE genotype. Family history of dementia was associated with worse manual dexterity in mid-life adulthood, but not with any other measures of cognitive ability or subclinical brain health in childhood and mid-life. These findings suggest that the association of family history with dementia risk is due chiefly to neurodegenerative rather than neurodevelopmental processes, and might first present with reduced motor skills.

我们旨在确定痴呆家族史与儿童和中年成年期大脑结构测量和认知表现的相关性。我们研究了 1,259 名父母（平均年龄：47.3 岁，范围 31.9-67.4）和他们的 866 名孩子（脑部 MRI 平均年龄 [范围] ：9.9 岁 [8.8-11.9]，认知年龄：13.5 岁 [12.6-15.8]）基于人群的 R 世代研究。父母填写了一份关于家族史的问卷，父母和孩子都接受了认知评估和神经影像学检查。在所有参与者中，109 名父母 （8.6%） 报告父母家族史为 痴呆，73 名儿童 （8.4%） 有 痴呆 岁祖父母病史，平均年龄为 痴呆75 岁 （± 7.3）。我们观察到父母或其子女的痴呆家族史与认知能力没有关联，除了与没有父母痴呆史的父母相比，普渡钉板更差（平均差 [95%CI]：-1.23 [-2.15;-0.31]，测试范围：21-52）。在父母和儿童中，神经影像学指标因家族史而异。结果不取决于年龄、性别和 APOE 基因型。痴呆家族史与成年中期手部灵活性较差有关，但与儿童和中年认知能力或亚临床大脑健康的任何其他指标无关。这些发现表明，家族史与痴呆风险的关联主要是由于神经退行性而不是神经发育过程，并且可能首先表现为运动技能降低。