Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
J Alzheimers Dis. 2023;91(1):233-243. doi: 10.3233/JAD-220600.
Mild cognitive impairment (MCI), a prodromal phase of Alzheimer's disease (AD), is heterogeneous with different rates and risks of progression to AD. There are significant gender disparities in the susceptibility, prognosis, and outcomes in patients with MCI, with female being disproportionately negatively impacted.
The aim of this study was to identify sex-specific heterogeneity of MCI using multi-modality data and examine the differences in the respective MCI subtypes with different prognostic outcomes or different risks for MCI to AD conversion.
A total of 325 MCI subjects (146 women, 179 men) and 30 relevant features were considered. Mixed-data clustering was applied to women and men separately to discover gender-specific MCI subtypes. Gender differences were compared in the respective subtypes of MCI by examining their MCI to AD disease prognosis, descriptive statistics, and conversion rates.
We identified three MCI subtypes: poor-, good-, and best-prognosis for women and for men, separately. The subtype-wise comparison (for example, poor-prognosis subtype in women versus poor-prognosis subtype in men) showed significantly different means for brain volumetric, cognitive test-related, also for the proportion of comorbidities. Also, there were substantial gender differences in the proportions of participants who reverted to normal function, remained stable, or converted to AD.
Analyzing sex-specific heterogeneity of MCI offers the opportunity to advance the understanding of the pathophysiology of both MCI and AD, allows stratification of risk in clinical trials of interventions, and suggests gender-based early intervention with targeted treatment for patients at risk of developing AD.
轻度认知障碍（MCI）是阿尔茨海默病（AD）的前驱阶段，具有不同的进展为 AD 的速度和风险，存在异质性。在 MCI 患者中，易感性、预后和结局存在显著的性别差异，女性受到的不利影响不成比例。
本研究旨在使用多模态数据识别 MCI 的性别特异性异质性，并检查具有不同预后结局或向 AD 转化风险不同的不同 MCI 亚型之间的差异。
共纳入 325 名 MCI 受试者（女性 146 名，男性 179 名）和 30 个相关特征。分别对女性和男性进行混合数据聚类，以发现性别特异性 MCI 亚型。通过检查各自 MCI 向 AD 疾病的预后、描述性统计和转化率，比较 MCI 各亚型中的性别差异。
我们确定了三种 MCI 亚型：女性和男性的预后较差、较好和最佳。亚型之间的比较（例如，女性的预后较差亚型与男性的预后较差亚型）显示，大脑容积、认知测试相关以及合并症比例的指标有显著不同的均值。此外，在恢复正常功能、保持稳定或向 AD 转化的参与者比例方面，也存在显著的性别差异。
分析 MCI 的性别特异性异质性为进一步了解 MCI 和 AD 的病理生理学提供了机会，允许对干预临床试验中的风险进行分层，并为处于发展为 AD 风险的患者提供基于性别的早期干预和靶向治疗。
