Oura Tatsushi, Tatekawa Hiroyuki, Takeda Akitoshi, Omori Ayako, Atsukawa Natsuko, Matsushita Shu, Horiuchi Daisuke, Takita Hirotaka, Shimono Taro, Ueda Daiju, Itoh Yoshiaki, Miki Yukio
Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
Department of Neurology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
medRxiv. 2025 May 9:2025.05.08.25327118. doi: 10.1101/2025.05.08.25327118.
No longitudinal imaging biomarkers have been validated to capture early glymphatic changes during disease-modifying therapy (DMT) for Alzheimer's disease (AD). This study investigated whether the diffusion tensor imaging along the perivascular space (DTI-ALPS) index can detect early treatment-related changes in participants with AD who initiate amyloid-targeting DMT.
Thirteen participants with AD (mean age, 72 years; 8 women) who initiated lecanemab therapy prospectively underwent DTI at baseline and three months. Projection and association fiber regions of interest, predefined in the HCP-1065 atlas, were inversely warped to the native space with vector-aware linear and non-linear registration, enabling a fully automated DTI-ALPS index calculation. Within-participant variances were obtained from 23 healthy volunteers in the OASIS dataset and used to set an equivalence margin of ±0.05 and determine a required sample size of 13. The primary end-point was equivalence of pre- and post-treatment DTI-ALPS indices (a two one-sided test; one-sided α = 0.05). Second, a paired -test was used to assess the changes. The intraclass correlation coefficients (ICCs) of the DTI-ALPS indices were also evaluated in identical machine environments and between different environments.
Baseline and three-month DTI-ALPS indices were 1.515 and 1.513, respectively. The mean change was 0.002 (90% confidence interval: -0.049, +0.045), entirely within the pre-specified margin; both one-sided -values were < 0.05, confirming statistical equivalence. A paired -test showed no significant difference ( = 0.94). Automated processing yielded perfect within-platform reproducibility (ICC = 1.00) and excellent cross-platform reliability (ICC = 0.99).
The DTI-ALPS index, an imaging metric associated with glymphatic activity, did not change during the first three months of lecanemab therapy. Although this finding suggests that glymphatic alterations may not be detectable early after treatment initiation, larger cohorts and longer follow-up periods are required to clarify the temporal relationship between DTI-ALPS index dynamics and therapeutic effects.
尚未有纵向成像生物标志物被证实可用于捕捉阿尔茨海默病（AD）疾病修饰治疗（DMT）期间早期的类淋巴系统变化。本研究调查了沿血管周围间隙的扩散张量成像（DTI-ALPS）指数是否能检测开始淀粉样蛋白靶向DMT治疗的AD参与者中与治疗相关的早期变化。
13名开始接受乐卡奈单抗治疗的AD参与者（平均年龄72岁；8名女性）在基线期和三个月时前瞻性地接受了DTI检查。在HCP-1065图谱中预定义的投射纤维和联合纤维感兴趣区域，通过矢量感知线性和非线性配准反向扭曲到原始空间，从而实现全自动的DTI-ALPS指数计算。参与者内部的方差来自OASIS数据集中的23名健康志愿者，并用于设置±0.05的等效性边界以及确定所需的样本量为13。主要终点是治疗前后DTI-ALPS指数的等效性（双侧单侧检验；单侧α = 0.05）。其次，使用配对t检验来评估变化。还在相同机器环境和不同环境之间评估了DTI-ALPS指数的组内相关系数（ICC）。
基线期和三个月时的DTI-ALPS指数分别为1.515和1.513。平均变化为0.002（90%置信区间：-0.049，+0.045），完全在预先指定的边界内；两个单侧p值均<0.05，证实了统计学等效性。配对t检验显示无显著差异（p = 0.94）。自动处理产生了完美的平台内可重复性（ICC = 1.00）和出色的跨平台可靠性（ICC = 0.99）。
DTI-ALPS指数是一种与类淋巴系统活动相关的成像指标，在乐卡奈单抗治疗的前三个月内没有变化。尽管这一发现表明在开始治疗后早期可能无法检测到类淋巴系统的改变，但需要更大的队列和更长的随访期来阐明DTI-ALPS指数动态变化与治疗效果之间的时间关系。
