Inguanzo Anna, Poulakis Konstantinos, Oltra Javier, Maioli Silvia, Marseglia Anna, Ferreira Daniel, Mohanty Rosaleena, Westman Eric
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Alzheimers Res Ther. 2025 Apr 11;17(1):79. doi: 10.1186/s13195-025-01713-x.
Longitudinal subtypes in Alzheimer's disease (AD) have been identified based on their distinct brain atrophy trajectories, encompassing mediotemporal and cortical pathways. These subtypes include minimal atrophy, limbic predominant, limbic predominant plus, diffuse atrophy and hippocampal sparing. The impact of sex on the progression of these subtypes remains a crucial area of investigation.
We analysed MRI data from 320 amyloid-β positive individuals with AD from three international cohorts (ADNI, J-ADNI and AIBL). Longitudinal clustering was conducted to identify atrophy trajectories over eight years from the clinical disease onset, with separate trajectories delineated for women and men.
Women consistently exhibited earlier hippocampal atrophy and a higher burden of white matter abnormalities compared to men, yet women displayed less cognitive decline over time. Additionally, specific risk factors and distinct neuropsychiatric symptoms were associated with sex within specific trajectories.
AD subtypes show sex-specific differences in disease progression, highlighting the need to account for these differences from the early disease stages. Integrating imaging biomarkers with sex differences can enable the identification of more precise treatments for each patient, ensuring that both women and men have equal access to tailored care.
阿尔茨海默病（AD）的纵向亚型已根据其不同的脑萎缩轨迹确定，包括中颞叶和皮质途径。这些亚型包括轻度萎缩型、边缘叶为主型、边缘叶为主加型、弥漫性萎缩型和海马保留型。性别对这些亚型进展的影响仍然是一个关键的研究领域。
我们分析了来自三个国际队列（ADNI、J-ADNI和AIBL）的320名淀粉样β蛋白阳性的AD患者的MRI数据。进行纵向聚类以确定从临床疾病发作起八年内的萎缩轨迹，并分别为女性和男性描绘不同的轨迹。
与男性相比，女性始终表现出更早的海马萎缩和更高的白质异常负担，但随着时间的推移，女性的认知衰退较少。此外，特定的风险因素和不同的神经精神症状与特定轨迹中的性别相关。
AD亚型在疾病进展中表现出性别特异性差异，突出了从疾病早期阶段就考虑这些差异的必要性。将成像生物标志物与性别差异相结合，可以为每位患者确定更精确的治疗方法，确保男性和女性都能平等获得量身定制的护理。
