Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain.
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Alzheimers Dement. 2018 Mar;14(3):340-351. doi: 10.1016/j.jalz.2017.09.013. Epub 2017 Oct 31.
Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD).
We included healthy control subjects (N = 254), mild cognitive impairment (N = 41), and AD dementia (N = 31) patients. Participants underwent a lumbar puncture and a 3 T magnetic resonance imaging. Healthy control subjects were classified following National Institute on Aging-Alzheimer's Association stages (stage 0, N = 220; stage 1, N = 25; and stage 2/3, N = 9). We assessed the cortical MD, cortical FW, and cortical thickness (CTh) changes along the AD continuum.
Microstructural and macrostructural changes show a biphasic trajectory. Stage 1 subjects showed increased CTh and decreased MD and FW with respect the stage 0 subjects. Stage 2/3 subjects showed decreased CTh and increased cortical MD and FW, changes that were more widespread in symptomatic stages.
These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification.
皮质平均扩散度（MD）和游离水分数（FW）的变化被认为是阿尔茨海默病（AD）的生物标志物。
我们纳入了健康对照组（N=254）、轻度认知障碍（MCI，N=41）和 AD 痴呆（N=31）患者。参与者接受了腰椎穿刺和 3T 磁共振成像检查。健康对照组根据美国国家老龄化研究所-阿尔茨海默病协会的阶段进行分类（阶段 0，N=220；阶段 1，N=25；阶段 2/3，N=9）。我们评估了 AD 连续体中皮质 MD、皮质 FW 和皮质厚度（CTh）的变化。
微观结构和宏观结构的变化呈现出双峰轨迹。与阶段 0 相比，阶段 1 患者的 CTh 增加，MD 和 FW 降低。阶段 2/3 患者的 CTh 降低，皮质 MD 和 FW 增加，这些变化在症状阶段更为广泛。
这些结果支持 AD 变化的双峰模型，这可能会影响临床试验中患者的选择以及磁共振成像作为疾病修饰的替代标志物的使用。
