A family history of Alzheimer's disease (AD) increases risk for AD in an individual by 1.5-to 3-fold. Heritability of AD risk may be due in part to the aggregation of neurodegeneration and cerebrovascular changes with cognitive endophenotypes within families. The purpose of this study was to determine the extent to which cognitive functioning in middle-aged adults is associated with objectively-measured neurodegenerative and cerebrovascular neuroimaging markers linked to risk for clinical AD in their parents, and the extent to which these associations differ by race/ethnicity and language, as proxy variables for social advantage. Middle-aged children enrolled in the Offspring study (n=356; 53.1±10.1 years old; 13% Non-Hispanic White, 27% Non-Hispanic Black, 26% Latinx tested in English, 34% Latinx tested in Spanish; 65% women; 13.5±3.4 years education) were administered the NIH Toolbox, a computerized neuropsychological battery, in their preferred language. Older adults were a subset of the Washington-Heights Inwood Columbia Aging Project (77.3±6.6 years old; 75% women; 10.0±4.6 years education) who underwent T1w- and T2w-MRI and who had a child enrolled in the Offspring study. We tested the associations of parental MRI measures reflecting neurodegeneration (hippocampal volume, cortical thickness) and cerebrovascular disease (white matter hyperintensity (WMH) volume, presence of infarct) with cognitive tests scores in Offspring participants. We further stratified the models by race/ethnicity. Better offspring cognitive scores aggregated lower parental neurodegeneration and cerebrovascular disease among Non-Hispanic White and Latinx participants, and with lower parental cerebrovascular disease alone among Non-Hispanic Black participants. Associations were generally strongest in Non-Hispanic White participants compared to the other groups. These results suggest a more consistent link between offspring cognitive endophenotype and parental brain health in intergenerational AD transmission among Non-Hispanic White participants compared to racial/ethnic and minority groups in which other social factors may be adding variance.

中文翻译：

---

具有种族和族裔差异的中年成年后代的认知内表型与阿尔茨海默氏病风险的父母磁共振成像生物标志物聚集在一起

阿尔茨海默氏病（AD）的家族病史会使个体患AD的风险增加1.5到3倍。AD风险的遗传性可能部分是由于家族内神经变性和脑血管变化以及认知内表型的聚集所致。这项研究的目的是确定中年成年人的认知功能与客观测量的神经退行性疾病和脑血管神经影像学标记物相关的程度，这些标记物与父母中临床AD的风险有关，以及这些相关性因种族而异的程度/民族和语言，作为获得社会利益的替代变量。参与后代研究的中年儿童（n = 356； 53.1±10.1岁； 13％非西班牙裔白人，27％非西班牙裔黑人，26％用英语测试拉丁语，34％用西班牙语测试拉丁语； 65％女性； 13.5±3。接受了4年的教育）以他们喜欢的语言管理了NIH Toolbox（计算机神经心理电池）。较高年龄的成年人是接受了T1w-和T2w-MRI检查并且有一个孩子参加了后代研究的Washington-Heights Inwood Columbia衰老项目的一个子集（77.3±6.6岁； 75％的女性； 10.0±4.6岁的教育）。我们在后代参与者中测试了反映神经变性（海马体积，皮层厚度）和脑血管疾病（白质高信号（WMH）体积，梗死的存在）的父母MRI测量与认知测试得分的关联。我们进一步根据种族/民族对模型进行了分层。在非西班牙裔白人和拉丁裔参与者中，更好的后代认知得分可聚合较低的父母神经变性和脑血管疾病，以及非西班牙裔黑人参与者中父母双亲较低的脑血管疾病。与其他组相比，非西班牙裔白人参与者的联想通常最强。这些结果表明，与其他种族因素可能增加差异的种族/族裔和少数群体相比，非西班牙裔白人参与者之间的代际AD传播中，后代认知内在表型与父母大脑健康之间的联系更加一致。