Crockett Rachel A, Casselton Charlotte, Howard Tatianna M, Wilkins Kevin B, Seo Gang, Brontë-Stewart Helen M
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
medRxiv. 2024 Jul 16:2024.07.16.24310492. doi: 10.1101/2024.07.16.24310492.
Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression.
187 participants were included in this study who were either healthy controls (HC; n=50) or had early mild cognitive impairment (EMCI; n=50), late MCI (LMCI; n=37), or AD (n=50). NBM volume was calculated using voxel-based morphometry and mean diffusivity (MD) of the lateral and medial NBM tracts were extracted using probabilistic tractography. Between group differences in NBM volume and tract MD were compared using linear mixed models controlling for age, sex, and either total intracranial volume or MD of a control mask, respectively. Associations between NBM volume and tract MD with executive function, memory, language, and visuospatial function were also analysed.
NBM volume was smallest in AD followed by LMCI (p<0.0001), with no difference between EMCI and HC. AD had highest MD for both tracts compared to all other groups (p<0.001). Both MCI groups had higher lateral tract MD compared to HC (p<0.05). Medial tract MD was higher in LMCI (p=0.008), but not EMCI (p=0.09) compared to HC. Higher lateral tract MD was associated with executive function (p=0.001) and language (p=0.02).
Integrity of the lateral NBM tract is most sensitive to the earliest stages of AD and should be considered an important therapeutic target for early detection and intervention.
迈内特基底核（NBM）萎缩是阿尔茨海默病（AD）的早期指标。然而，与NBM体积相比，NBM白质束完整性降低可能与认知障碍及向痴呆进展更为相关。需要开展研究，比较AD进展早期和晚期NBM体积以及外侧和内侧NBM束完整性的差异。
本研究纳入了187名参与者，他们要么是健康对照（HC；n = 50），要么患有早期轻度认知障碍（EMCI；n = 50）、晚期MCI（LMCI；n = 37）或AD（n = 50）。使用基于体素的形态学测量法计算NBM体积，并使用概率纤维束成像提取外侧和内侧NBM束的平均扩散率（MD）。分别使用控制年龄、性别以及总颅内体积或对照掩码MD的线性混合模型，比较组间NBM体积和束MD的差异。还分析了NBM体积和束MD与执行功能、记忆、语言和视觉空间功能之间的关联。
AD组的NBM体积最小，其次是LMCI组（p < 0.0001），EMCI组和HC组之间无差异。与所有其他组相比，AD组两条束的MD最高（p < 0.001）。与HC组相比，两个MCI组的外侧束MD均较高（p < 0.05）。与HC组相比，LMCI组的内侧束MD较高（p = 0.008），而EMCI组则无差异（p = 0.09）。较高的外侧束MD与执行功能（p = 0.001）和语言（p = 0.02）相关。
外侧NBM束的完整性对AD的最早阶段最为敏感，应被视为早期检测和干预的重要治疗靶点。
