Cynical hostility (CH), a specific dimension of hostility that consists of a mistrust of others, has been suggested as a high-risk trait for dementia. However, the influence of CH on the incidence of Alzheimer's disease (AD) remains poorly understood. This study investigated whether late-life CH is associated with AD risk and structural neuroimaging markers of AD.

In community-dwelling older adults from the French ESPRIT cohort (n = 1388), incident dementia rate according to CH level was monitored during an 8-year follow-up and analyzed using Cox proportional hazards regression models. Brain magnetic resonance imaging volumes were measured at baseline (n = 508). Using automated segmentation procedures (Freesurfer 6.0), the authors assessed brain grey and white volumes on all magnetic resonance imaging scans. They also measured white matter hyperintensities volumes using semi-automated procedures. Mean volumes according to the level of CH were compared using ANOVA.

Eighty-four participants developed dementia (32 with AD). After controlling for potential confounders, high CH was predictive of AD (HR 2.74; 95% CI 1.10–6.85; p = 0.030) and all dementia types are taken together (HR 2.30; 95% CI 1.10–4.80; p = 0.027). High CH was associated with white matter alterations, particularly smaller anterior corpus callosum volume (p < 0.01) after False Discovery Rate correction, but not with grey matter volumes.

High CH in late life is associated with cerebral white matter alterations, designated as early markers of dementia, and higher AD risk. Identifying lifestyle and biological determinants related to CH could provide clues on AD physiopathology and avenues for prevention strategies.

愤世嫉俗的敌意 (CH) 是一种特定的敌意，包括对他人的不信任，被认为是痴呆症的高风险特征。然而，CH 对阿尔茨海默病 (AD) 发病率的影响仍然知之甚少。本研究调查晚年 CH 是否与 AD 风险和 AD 的结构神经影像学标志物相关。

在来自法国 ESPRIT 队列（ n = 1388）的社区居住的老年人中，在 8 年的随访期间根据 CH 水平监测痴呆发生率，并使用 Cox 比例风险回归模型进行分析。在基线时测量脑磁共振成像体积 ( n = 508)。使用自动分割程序 (Freesurfer 6.0)，作者评估了所有磁共振成像扫描的大脑灰色和白色体积。他们还使用半自动程序测量了白质高强度体积。使用 ANOVA 比较根据 CH 水平的平均体积。

84 名参与者患上了痴呆症（32 名患有 AD）。控制潜在的混杂因素后，高 CH 可预测 AD（HR 2.74；95% CI 1.10–6.85；p = 0.030），所有痴呆类型综合考虑（HR 2.30；95% CI 1.10–4.80；p = 0.027）。高 CH 与白质改变相关，特别是在错误发现率校正后较小的前胼胝体体积 ( p < 0.01)，但与灰质体积无关。

晚年高 CH 与大脑白质改变有关，被指定为痴呆的早期标志，并增加 AD 风险。确定与 CH 相关的生活方式和生物学决定因素可以为 AD 病理生理学提供线索，并为预防策略提供途径。