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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认知未受损老年人的记忆障碍和 β-淀粉样蛋白父母史


重要性研究表明，母亲（而非父亲）的晚发性阿尔茨海默病史使个体容易出现较高的大脑 β-淀粉样蛋白 (Aβ) 负担、脑代谢降低和灰质体积较低。脑 Aβ 正电子发射断层扫描 (Aβ-PET) 和认知功能未受损的大样本老年人的基线认知方面的术语。 设计、设置和参与者这项横断面研究利用了 4413 名接受抗淀粉样蛋白治疗筛查的个体的数据无症状阿尔茨海默病 (A4) 研究是一项在美国、澳大利亚、加拿大和日本 67 个地点进行的随机临床试验，旨在预防阿尔茨海默病。数据收集于 2014 年 4 月至 2017 年 12 月期间，分析时间为 2022 年 12 月至 2023 年 6 月。参与者是年龄在 65 岁至 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），接受 PET 成像以评估皮质 Aβ 水平是否符合试验资格。总共筛查了 4492 名参与者，排除了 79 名缺失数据。 主要结果和措施收集了人口统计学特征（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出现时的年龄作为变量。根据连续新皮质 18F-氟倍他吡 Aβ-PET 和临床前阿尔茨海默认知综合测试来评估父母病史。 结果 4413 名个体（平均 [SD] 年龄，71.27 [4.66] 岁，2617 名女性 [59.3%]），平均 Aβ-PET父母双方均有记忆障碍史的个体中，该值升高（n = 455；平均 [SD] 标准化摄取值比 [SUVR] = 1.12 [0.19]； Wilcoxon P = 1.1 × 10−5) 以及仅有母亲病史的患者 (n = 1772；平均 [SD] SUVR = 1.10 [0.19]；Wilcoxon P = 2.70 × 10−5) 与仅有父亲病史的患者 (n = 1772；平均 [SD] SUVR = 1.10 [0.19]；Wilcoxon P = 2.70 × 10−5) 相比= 632；平均 [SD] SUVR = 1.08 [0.18]；Wilcoxon P = 1.1 × 10−5）或无家族史（n = 1554；平均 [SD] SUVR = 1.08 [0.19]；Wilcoxon P = 1.1 × 10− 5）。父亲有早发性记忆障碍（年龄 <65 岁）史，但与晚发性记忆障碍（年龄≥65 岁）无关，与参与者 Aβ-PET 升高相关（平均 [SD] SUVR = 1.19 [0.21]；P = 3.00 × 10−6）与无父亲史（平均[SD] SUVR = 1.09 [0.19]）相比，而早发型和晚发型组中，母亲史与Aβ升高相关。与认知没有关联。结论和相关性在这项研究中，母亲的早发性记忆障碍史（任何年龄）和父亲的早发性记忆障碍史与无症状老年人中的 Aβ 负荷相关。特定性别的父母史可能有助于临床医生了解后代 Aβ 负担的可能性，并有助于在疾病的最早阶段识别高风险个体以进行预防。