Andrews Shea J, Jonson Caroline, Fulton-Howard Brian, Renton Alan E, Yokoyama Jennifer S, Yaffe Kristine
Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, USA.
Department of Neurology, University of California San Francisco, San Francisco, USA.
medRxiv. 2024 Apr 30:2024.04.27.24306488. doi: 10.1101/2024.04.27.24306488.
By integrating genetic and clinical risk factors into genomic-informed dementia risk reports, healthcare providers can offer patients detailed risk profiles to facilitate understanding of individual risk and support the implementation of personalized strategies for promoting brain health.
To develop a genomic-informed risk assessment composed of family history, genetic, and clinical risk factors and, in turn, evaluate how the risk assessment predicted incident dementia.
This longitudinal study included data from two clinical case-control cohorts with an average of 6.6 visits. Secondary analyses were conducted from July 2023 - March 2024.
Data were previously collected across multiple US locations from 1994 to 2023.
Older adults aged 55+ with whole-genome sequencing and dementia-free at baseline.
An additive score comprising the modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (mCAIDE), family history of dementia, genotype, and an AD polygenic risk score.
The risk of progression to all-cause dementia was evaluated using Cox-proportional hazard models (hazard ratios with 95% confidence intervals [OR 9%CI]).
A total of 3,429 older adults were included (aged 75 ± 7 years; 59% female; 75% non-Latino White, 15% Black, 5.2% Latino, 3.6% other, and 0.4% Asian; 27% MCI), with 751 participants progressing to dementia. The most common high-risk indicator was a family history of dementia (56%), followed by *ε4 genotype (36%), high mCAIDE score (34%), and high AD-PRS (11%). Most participants had at least one high-risk indicator, with 39% having one, 32% two, 9.8% three, and 1% four. The presence of 1, 2, 3, or 4 risk indicators was associated with a doubling (HR = 1.72, CI: 1.34-2.22, p = 2.5e-05), tripling (HR = 3.09, CI: 2.41-3.95, p = 4.4e-19), quadrupling (HR = 4.46, CI: 3.34-5.94, p = 2.2e-24), and a twelvefold increase (HR = 12.15, CI: 7.33-20.14, p = 3.2e-22) in dementia risk.
CONCLUSION & RELEVANCE: We found that most participants in memory and aging clinics had at least one high-risk indicator for dementia. Furthermore, we observed a dose-response relationship where a greater number of risk indicators was associated with an increased risk of incident dementia.
通过将遗传和临床风险因素整合到基于基因组信息的痴呆症风险报告中，医疗保健提供者可以为患者提供详细的风险概况，以帮助他们了解个人风险，并支持实施促进大脑健康的个性化策略。
开发一种由家族史、遗传和临床风险因素组成的基于基因组信息的风险评估方法，进而评估该风险评估如何预测痴呆症的发病情况。
这项纵向研究纳入了来自两个临床病例对照队列的数据，平均进行了6.6次随访。于2023年7月至2024年3月进行了二次分析。
数据先前于1994年至2023年在美国多个地点收集。
年龄在55岁及以上、进行了全基因组测序且基线时无痴呆症的老年人。
一个综合评分，包括改良的心血管危险因素、衰老和痴呆症发病风险评分（mCAIDE）、痴呆症家族史、基因型以及阿尔茨海默病多基因风险评分。
使用Cox比例风险模型（风险比及95%置信区间[OR 9%CI]）评估进展为全因性痴呆症的风险。
共纳入3429名老年人（年龄75±7岁；59%为女性；75%为非西班牙裔白人，15%为黑人，5.2%为西班牙裔，3.6%为其他，0.4%为亚洲人；27%为轻度认知障碍），其中751名参与者进展为痴呆症。最常见的高风险指标是痴呆症家族史（56%），其次是ε4基因型（36%）、高mCAIDE评分（34%）和高AD-PRS（11%）。大多数参与者至少有一项高风险指标，其中39%有一项，32%有两项，9.8%有三项，1%有四项。存在1、2、3或4项风险指标与痴呆症风险加倍（HR = 1.72，CI：1.34 - 2.22，p = 2.5e - 05）、增至三倍（HR = 3.09，CI：2.41 - 3.95，p = 4.4e - 19）、增至四倍（HR = 4.46，CI：3.34 - 5.94，p = 2.2e - 24）以及增至十二倍（HR = 12.15，CI：7.33 - 20.14，p = 3.2e - 22）相关。
我们发现，记忆与衰老诊所中的大多数参与者至少有一项痴呆症高风险指标。此外，我们观察到一种剂量反应关系，即风险指标数量越多，痴呆症发病风险越高。
