ImportanceStudies have suggested that maternal history of late-onset Alzheimer disease, but not paternal, predisposes individuals to higher brain β-amyloid (Aβ) burden, reduced brain metabolism, and lower gray matter volumes.ObjectiveTo characterize maternal vs paternal history of memory impairment in terms of brain Aβ-positron emission tomography (Aβ-PET) and baseline cognition among a large sample of cognitively unimpaired older adults.Design, Setting, and ParticipantsThis cross-sectional study leveraged data from 4413 individuals who were screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study, a randomized clinical trial conducted across 67 sites in the US, Australia, Canada, and Japan aimed at Alzheimer disease prevention. Data were collected between April 2014 and December 2017 and analyzed from December 2022 to June 2023. Participants were cognitively unimpaired adults (Clinical Dementia Rating = 0 and/or Mini-Mental State Examination score ≥25) between the ages of 65 and 85 years who underwent PET imaging to assess cortical Aβ levels for trial eligibility. A total of 4492 participants were screened, and 79 missing data were excluded.Main Outcomes and MeasuresDemographic characteristics (eg, age, sex, education), apolipoprotein E genotyping, participant-reported parental history of memory impairment and parental age at symptom onset were collected as variables. Parental history was assessed in terms of continuous neocortical 18F-florbetapir Aβ-PET and the Preclinical Alzheimer Cognitive Composite.ResultsOf 4413 individuals (mean [SD] age, 71.27 [4.66] years, 2617 women [59.3%]), mean Aβ-PET was elevated in individuals with history of memory impairment in both parents (n = 455; mean [SD] standardized uptake value ratio [SUVR] = 1.12 [0.19]; Wilcoxon P = 1.1 × 10−5) and in those with only maternal history (n = 1772; mean [SD] SUVR = 1.10 [0.19]; Wilcoxon P = 2.70 × 10−5) compared with those with only paternal history (n = 632; mean [SD] SUVR = 1.08 [0.18]; Wilcoxon P = 1.1 × 10−5) or no family history (n = 1554; mean [SD] SUVR = 1.08 [0.19]; Wilcoxon P = 1.1 × 10−5). Paternal history of early-onset memory impairment (age <65 years) but not late-onset (age ≥65 years) was associated with elevated participant Aβ-PET (mean [SD] SUVR = 1.19 [0.21]; P = 3.00 × 10−6) in comparison with no paternal history (mean [SD] SUVR = 1.09 [0.19]) whereas maternal history was associated with elevated Aβ in both early-onset and late-onset groups. There was no association with cognition.Conclusions and RelevanceIn this study, maternal history (at any age) and paternal history of early-onset memory impairment were associated with Aβ burden among asymptomatic older individuals. Sex-specific parental history may help inform clinicians on likelihood of Aβ burden in offspring and help identify high-risk individuals at the earliest stages of disease for prevention.

中文翻译：

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认知能力未受损的老年人的父母记忆障碍和 β-淀粉样蛋白病史


重要性研究表明，母系迟发性阿尔茨海默病史（而不是父系病史）使个体易患较高的脑 β-淀粉样蛋白 （Aβ） 负荷、脑代谢减少和灰质体积降低。目的根据脑 Aβ-正电子发射断层扫描 （Aβ-PET） 和大样本认知未受损老年人的基线认知来描述母系与父系的记忆障碍史。设计、设置和参与者这项横断面研究利用了 4413 名接受无症状阿尔茨海默病 （A4） 抗淀粉样蛋白治疗筛查的个体的数据，这是一项在美国、澳大利亚、加拿大和日本的 67 个地点进行的随机临床试验，旨在预防阿尔茨海默病。数据是在 2014 年 4 月至 2017 年 12 月期间收集的，并在 2022 年 12 月至 2023 年 6 月期间进行了分析。参与者是年龄在 65 至 85 岁之间的认知未受损的成年人 （临床痴呆评分 = 0 和/或简易精神状态检查评分 ≥25），他们接受了 PET 成像以评估皮质 Aβ 水平是否符合试验资格。共筛选了 4492 名参与者，排除了 79 名缺失数据。主要结局和措施人口统计学特征 （例如，年龄、性别、教育程度）、载脂蛋白 E 基因分型、参与者报告的父母记忆障碍史和父母症状发作时的年龄作为变量收集。根据连续新皮层 18F-florbetapir Aβ-PET 和临床前阿尔茨海默病认知复合体评估父母病史.结果在 4413 名个体 （平均 [SD] 年龄，71.27 [4.66] 岁，2617 名女性 [59.3%]）中，父母双方都有记忆障碍病史的个体的平均 Aβ-PET 升高 （n = 455;平均 [SD] 标准化摄取值比 [SUVR] = 1.12 [0.19];Wilcoxon P = 1.1 × 10−5）和只有母系病史的人群 （n = 1772;平均值 [SD] SUVR = 1.10 [0.19];Wilcoxon P = 2.70 × 10−5） 与只有父系病史的人 （n = 632;平均值 [SD] SUVR = 1.08 [0.18];Wilcoxon P = 1.1 × 10−5）或无家族史 （n = 1554;平均值 [SD] SUVR = 1.08 [0.19];Wilcoxon P = 1.1 × 10−5）。父亲早发性记忆障碍病史（年龄 <65 岁）但不与晚发性 （年龄 ≥65） 与参与者 Aβ-PET 升高相关 （平均值 [SD] SUVR = 1.19 [0.21];P = 3.00 × 10−6），与无父系病史 （平均值 [SD] SUVR = 1.09 [0.19]） 相比，而早发性和晚发组的母体病史与 Aβ 升高相关。与认知无关。结论和相关性在本研究中，母亲病史 （任何年龄） 和父亲早发性记忆障碍史与无症状老年人的 Aβ 负荷相关。性别特异性父母史可能有助于临床医生了解后代 Aβ 负荷的可能性，并有助于在疾病的早期阶段识别高危个体以进行预防。