Validating the role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a genetic risk score in progression to cognitive impairment in a population-based cohort of older adults followed for 12 years
Validating the role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a genetic risk score in progression to cognitive impairment in a population-based cohort of older adults followed for 12 years
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DOI：
10.1186/s13195-017-0240
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发表时间：
2017-03-04
影响因子：
9
通讯作者：
Anstey, Kaarin J.
中科院分区：
文献类型：
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作者：
Andrews, Shea J.;Eramudugolla, Ranmalee;Anstey, Kaarin J.
背景资料：到2050年，痴呆症患者人数预计将超过1.3亿，这将对个人、社会和经济产生严重影响。采用以疾病预防为重点的成功干预和治疗策略是目前唯一可以对痴呆症预测率产生影响的方法，风险评估是基于人口的风险降低的关键组成部分，用于识别风险个体。我们评估了包括生活方式、医疗和人口因素在内的风险指数（澳大利亚国立大学阿尔茨海默病风险指数[ANU-ADRI]），以及遗传风险评分（GRS），用于评估进展为轻度认知障碍（MCI）的风险。方法：计算ANU-ADRI用于人格和全面健康（PATH）贯穿生命项目中的2078名参与者的基线评估。GRS是基于先前与阿尔茨海默病（AD）相关的25个单核苷酸多态性构建的。在12年的随访中，对参与者进行了临床诊断的MCI和痴呆以及基于心理测量测试的MCI（MCI-TB）评估。根据基线ANU-ADRI和GRS.Results，使用多状态模型估计12年内从认知正常（CN）向MCI、痴呆和MCI-TB转变的几率：较高的ANU-ADRI评分与从CN向MCI和MCI-TB进展的风险增加相关（HR 1.07 [95%CI 1.04-1.11]; 1.07 [1.04-1.09]）。GRS与从CN到痴呆的转变相关（HR 4.19 [95% CI 1.72-10.20]），但与MCI或MCI-TB无关（HR 1.05 [95% CI 0.86-1.29]; 1.03 [0.87-1.21]）。我们研究的局限性包括PATH项目参与者的种族主要是高加索人，这可能限制了本研究结果对其他种族人群的普遍性。AD的生物标志物无法用于定义归因于AD的MCI。在PATH项目中，并非所有的ANU-ADRI预测变量都可用。结论：在一般人群中，包括生活方式、医学和人口统计学因素的ANU-ADRI与从CN进展为MCI的风险相关，而包括主要AD风险基因的GRS与该风险无关。ANU-ADRI可用于人群水平的风险评估和筛查。
Background: The number of people living with dementia is expected to exceed 130 million by 2050, which will have serious personal, social and economic implications. Employing successful intervention and treatment strategies focused on disease prevention is currently the only available approach that can have an impact on the projected rates of dementia, with risk assessment being a key component of population-based risk reduction for identification of at-risk individuals. We evaluated a risk index comprising lifestyle, medical and demographic factors (the Australian National University Alzheimer's Disease Risk Index [ANU-ADRI]), as well as a genetic risk score (GRS), for assessment of the risk of progression to mild cognitive impairment (MCI).Methods: The ANU-ADRI was computed for the baseline assessment of 2078 participants in the Personality and Total Health (PATH) Through Life project. GRSs were constructed on the basis of 25 single-nucleotide polymorphisms previously associated with Alzheimer's disease (AD). Participants were assessed for clinically diagnosed MCI and dementia as well as psychometric test-based MCI (MCI-TB) at 12 years of follow-up. Multi-state models were used to estimate the odds of transitioning from cognitively normal (CN) to MCI, dementia and MCI-TB over 12 years according to baseline ANU-ADRI and GRS.Results: A higher ANU-ADRI score was associated with increased risk of progressing from CN to both MCI and MCI-TB (HR 1.07 [95% CI 1.04-1.11]; 1.07 [1.04-1.09]). The GRS was associated with transitions from CN to dementia (HR 4.19 [95% CI 1.72-10.20), but not to MCI or MCI-TB (HR 1.05 [95% CI 0.86-1.29]; 1.03 [0.87-1.21]). Limitations of our study include that the ethnicity of participants in the PATH project is predominately Caucasian, potentially limiting the generalisability of the results of this study to people of other ethnicities. Biomarkers of AD were not available to define MCI attributable to AD. Not all the predictive variables for the ANU-ADRI were available in the PATH project. (Continued on next page)Continued from previous page)Conclusions: In the general population, the ANU-ADRI, comprising lifestyle, medical and demographic factors, is associated with the risk of progression from CN to MCI, whereas a GRS comprising the main AD risk genes was not associated with this risk. The ANU-ADRI may be used for population-level risk assessment and screening.