Andrews Shea J, Eramudugolla Ranmalee, Velez Jorge I, Cherbuin Nicolas, Easteal Simon, Anstey Kaarin J
John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health Australian National University, The Australian National University Florey, Building 54, Mills Road, Acton ACT 2601, Canberra, Australia.
Alzheimers Res Ther. 2017 Mar 4;9(1):16. doi: 10.1186/s13195-017-0240-3.
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).
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.
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.
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.
预计到2050年，痴呆症患者数量将超过1.3亿，这将产生严重的个人、社会和经济影响。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能够对预计的痴呆症发病率产生影响的方法，风险评估是基于人群的风险降低以识别高危个体的关键组成部分。我们评估了一个包含生活方式、医学和人口统计学因素的风险指数（澳大利亚国立大学阿尔茨海默病风险指数[ANU-ADRI]）以及一个遗传风险评分（GRS），用于评估进展为轻度认知障碍（MCI）的风险。
计算了“贯穿一生的个性与总体健康（PATH）”项目中2078名参与者基线评估时的ANU-ADRI。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了GRS。在随访12年时，对参与者进行临床诊断的MCI和痴呆以及基于心理测量测试的MCI（MCI-TB）评估。使用多状态模型根据基线ANU-ADRI和GRS估计12年内从认知正常（CN）转变为MCI、痴呆和MCI-TB的几率。
较高的ANU-ADRI评分与从CN进展为MCI和MCI-TB的风险增加相关（风险比1.07[95%置信区间1.04-1.11]；1.07[1.04-1.09]）。GRS与从CN转变为痴呆相关（风险比4.19[95%置信区间1.72-10.20]），但与MCI或MCI-TB无关（风险比1.05[95%置信区间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白种人，这可能限制了本研究结果对其他种族人群的适用性。没有可用的AD生物标志物来定义由AD引起的MCI。PATH项目中并非所有ANU-ADRI的预测变量都可用。
在一般人群中，包含生活方式、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，而包含主要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。
