Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Wellcome Centre for Integrative Neuroimaging, Oxford, United Kingdom.
PLoS One. 2019 Feb 19;14(2):e0211273. doi: 10.1371/journal.pone.0211273. eCollection 2019.
There is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer's disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging.
We included 550 older adults participating in the Whitehall II study with longitudinal data, cognitive test results, and multi-modal MRI. Hippocampal atrophy was defined as Scheltens Scores >0. Resilient individuals (n = 184) were defined by high cognitive performance despite hippocampal atrophy (HA). Non-resilient participants (n = 133) were defined by low cognitive performance (≥1.5 standard deviations (S.D.) below the group mean) in the presence of HA. Dynamic and static exposures were evaluated for their ability to predict later resilience status using multivariable logistic regression. In a brain-wide analysis we tested for group differences in the integrity of white matter (structural connectivity) and resting-state networks (functional connectivity).
Younger age (OR: 0.87, 95% CI: 0.83 to 0.92, p<0.001), higher premorbid FSIQ (OR: 1.06, 95% CI: 1.03 to 1.10, p<0.0001) and social class (OR 1 vs. 3: 4.99, 95% CI: 1.30 to 19.16, p = 0.02, OR 2 vs. 3: 8.43, 95% CI: 1.80 to 39.45, p = 0.007) were independently associated with resilience. Resilient individuals could be differentiated from non-resilient participants by higher fractional anisotropy (FA), and less association between anterior and posterior resting state networks. Higher FA had a significantly more positive effect on cognitive performance in participants with HA, compared to those without.
Resilient individuals could be distinguished from those who developed impairments on the basis of sociodemographic characteristics, brain structural and functional connectivity, but not midlife lifestyles. There was a synergistic deleterious effect of hippocampal atrophy and poor white matter integrity on cognitive performance. Exploiting and supporting neural correlates of resilience could offer a fresh approach to postpone or avoid the appearance of clinical symptoms.
结构脑异常的临床表现存在显著异质性，包括阿尔茨海默病生物标志物。尽管存在风险因素或病理性脑改变，一些个体仍能保持记忆，这表明存在韧性。我们旨在使用社会人口统计学变量和神经影像学来测试是否可以区分出具有韧性的个体和发展为认知障碍的个体。
我们纳入了 550 名参与白厅 II 研究的老年人，这些老年人具有纵向数据、认知测试结果和多模态 MRI。海马萎缩的定义为 Scheltens 评分>0。具有韧性的个体（n=184）是指尽管存在海马萎缩（HA），但认知表现较高。非韧性参与者（n=133）的定义是认知表现较低（低于组平均值的 1.5 个标准差），同时存在 HA。使用多变量逻辑回归评估动态和静态暴露对以后的韧性状态的预测能力。在脑全分析中，我们测试了白质完整性（结构连接）和静息状态网络（功能连接）的组间差异。
较年轻的年龄（OR：0.87，95%CI：0.83 至 0.92，p<0.001）、较高的预患病 FSIQ（OR：1.06，95%CI：1.03 至 1.10，p<0.0001）和社会阶层（OR 1 与 3：4.99，95%CI：1.30 至 19.16，p=0.02，OR 2 与 3：8.43，95%CI：1.80 至 39.45，p=0.007）与韧性独立相关。通过更高的分数各向异性（FA）和前后静息状态网络之间的关联较少，可以将具有韧性的个体与非韧性参与者区分开来。与没有 HA 的参与者相比，在有 HA 的参与者中，较高的 FA 对认知表现有更显著的积极影响。
可以根据社会人口统计学特征、脑结构和功能连接来区分具有韧性的个体和发展为认知障碍的个体，但不能区分中年生活方式。海马萎缩和白质完整性差对认知表现有协同的有害影响。利用和支持韧性的神经相关性可能为推迟或避免出现临床症状提供新的方法。
