Improving risk indexes for Alzheimer's disease and related dementias for use in midlife.
Improving risk indexes for Alzheimer's disease and related dementias for use in midlife.
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DOI：
10.1093/braincomms/fcac223
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发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
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需要了解一个人患阿尔茨海默病和相关痴呆症（ADRD）的风险，以便对预防干预，监测和治疗试验的候选人进行分类。ADRD风险指数就是为此目的而存在的，但每个指数只包括已知风险因素的一个子集。公布的指数中缺失的信息可以改善风险预测。在对新西兰人口代表性出生队列进行的达尼丁研究中（N = 938，49.5%为女性），我们将四个主要风险指数与ADRD中年前因的相关性与一个由几乎所有已知ADRD风险因素组成的新型基准指数进行了比较，即达尼丁ADRD风险基准（DunedinARB）。现有的指标包括心血管风险因素、衰老和痴呆指数（CAIDE）、脑健康指数生活方式（LIBRA）、澳大利亚国立大学阿尔茨海默病风险指数（ANU-ADRI）和柳叶刀痴呆症委员会选择的风险。达尼丁基准由48个独立的风险指标组成，分为10个概念上不同的风险领域。作为结局指标的ADRD中年前因包括年龄-45岁的脑结构完整性指标[磁共振成像评估：（i）机器学习算法估计的脑年龄，（ii）白色物质高强度的对数转换体积，和（iii）海马体的平均灰质体积]和脑功能完整性的测量[（i）通过Wechsler成人智力量表评估的客观认知功能-（ii）日常认知功能的主观问题，以及（iii）客观认知下降，以匹配的Weschler智力量表上从童年到中年的认知评分的剩余变化来衡量。所有的指标都被定量分布，并证明了关于ADRD的中年前因的信息，包括算法估计的脑年龄（β为0.16 - 0.22），白色物质高信号体积（β为0.16至0.19），海马体积（β值为-0.08至-0.11），测试认知缺陷（β从-0.36到-0.49），日常认知问题（β从0.14到0.38）和纵向认知下降（β从-0.18到-0.26）。现有的指标相比，有利的综合基准，在他们的关联与大脑结构的完整性措施，但优于他们的关联与功能的完整性措施，特别是主观认知问题和测试的认知能力下降。结果表明，现有的指标可以通过有针对性的补充来改善，特别是评估社会经济地位，身体和感觉功能，表观遗传衰老和主观整体健康的措施。现有的发病前ADRD风险指数在识别中年一般人群中的线性风险梯度方面表现良好，即使它们只包括一小部分潜在风险因素。然而，它们可以通过有针对性的增加来改进，以更全面地捕捉这种多重决定的年龄相关疾病的不同风险方面。Reuben等人报告说，现有的痴呆症风险指数在痴呆症症状出现前几十年就能提供关于普通人群大脑健康的信息，即使这些指数只包括潜在风险的一部分。与一种新的综合风险基准的比较表明，有针对性的风险因素的增加可以改善对风险个体的选择。
Knowledge of a person’s risk for Alzheimer’s disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife (N = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age (β's from 0.16 to 0.22), white matter hyperintensities volume (β's from 0.16 to 0.19), hippocampal volume (β's from −0.08 to −0.11), tested cognitive deficits (β's from −0.36 to −0.49), everyday cognitive problems (β's from 0.14 to 0.38), and longitudinal cognitive decline (β's from −0.18 to −0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease. Reuben et al. report that existing dementia-risk indexes are informative about brain health in the general population decades before dementia symptoms emerge, even when the indexes include only a subset of potential risks. Comparisons to a novel comprehensive risk-benchmark indicated that targeted risk-factor additions could improve the selection of at-risk individuals.
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影响因子：
11
作者：
Elliott, Maxwell L.;Belsky, Daniel W.;Hariri, Ahmad R.
通讯作者：
Hariri, Ahmad R.
影响因子：
9.9
作者：
Devanand, D. P.;Lee, Seonjoo;Mayeux, Richard
通讯作者：
Mayeux, Richard
DOI：
10.1024/1662-9647/a000074
发表时间：
2012-12-01
影响因子：
1
作者：
Franke, Katja;Gaser, Christian
通讯作者：
Gaser, Christian
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
--
作者：
Elias, MF;Beiser, A;D'Agostino, RB
通讯作者：
D'Agostino, RB