White matter hyperintensities and imaging patterns of brain ageing in the general population
White matter hyperintensities and imaging patterns of brain ageing in the general population
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DOI：
10.1093/brain/aww008
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发表时间：
2016-04-01
期刊：
影响因子：
14.5
通讯作者：
Davatzikos, Christos
中科院分区：
文献类型：
--
作者：
Habes, Mohamad;Erus, Guray;Davatzikos, Christos
白质高信号与痴呆和认知能力下降的风险增加有关。目前的研究调查了波美拉尼亚健康研究中涵盖广泛年龄范围（20-90 岁）的大量人口样本（n = 2367）中白质高信号负担与与大脑衰老和阿尔茨海默病相关的脑萎缩模式之间的关系。我们使用自动分割量化白质高信号，并使用机器学习方法总结萎缩模式，得出两个指数：SPARE-BA 指数（捕获与年龄相关的脑萎缩）和 SPARE-AD 指数（之前开发用于捕获阿尔茨海默病患者中发现的萎缩模式）。在脑室周围和深部白质区域发现了与年龄相关的白质高信号积累的特征模式。与白质高信号负荷低的个体相比，白质高信号负荷高的个体表现出显着（P < 0.0001）较低的 SPARE-BA 和较高的 SPARE-AD 值，表明前者在通常受衰老和阿尔茨海默氏病痴呆影响的大脑区域有更多的萎缩模式。为了研究白质高信号的可能因果关系，使用结构方程模型来量化 Framingham 心血管疾病风险评分和白质高信号负担对 SPARE-BA 的影响，揭示了它们之间具有统计显着性 (P < 0.0001) 的因果关系。结构方程模型显示，年龄对 SPARE-BA 的影响是由白质高信号和心血管风险评分介导的，分别解释了 10.4% 和 21.6% 的方差。直接年龄效应解释了 SPARE-BA 方差的 70.2%。只有白质高信号显着介导了 SPARE-AD 的年龄效应，解释了 32.8% 的方差。直接年龄效应解释了 SPARE-AD 方差的 66.0%。多变量回归显示白质高信号体积与高血压（P = 0.001）、糖尿病（P = 0.023）、吸烟（P = 0.002）和教育水平（P = 0.003）之间存在显着关系。与认知测试的唯一显着关联是与加州言语和学习记忆测试的立即回忆。与 APOE 基因型不存在显着关联。这些结果支持这样的假设：白质高信号会导致普通人群大脑超常老化中发现的脑萎缩模式。白质高信号也会导致与阿尔茨海默病痴呆相关区域的脑萎缩模式，这与已知的白质高信号对痴呆可能性的附加作用一致。降低患心血管疾病和白质高信号的几率的预防策略可以降低痴呆症的发病率或延迟其发作。
White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE-AD variance. Multivariable regression showed significant relationship between white matter hyperintensities volume and hypertension (P = 0.001), diabetes mellitus (P = 0.023), smoking (P = 0.002) and education level (P = 0.003). The only significant association with cognitive tests was with the immediate recall of the California verbal and learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia.