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; Institute of Biomedical Engineering, University of Oxford, Oxford, UK.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States.
Neurobiol Dis. 2024 Oct 15;201:106677. doi: 10.1016/j.nbd.2024.106677. Epub 2024 Sep 21.
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 < 0.01). 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.
梅内尔基底核萎缩（NBM）是阿尔茨海默病（AD）的早期指标。然而，与 NBM 体积相比，NBM 白质束的完整性降低可能与认知障碍和向痴呆进展更为相关。需要研究比较 AD 进展的早期和晚期阶段 NBM 体积和外侧和内侧 NBM 束完整性的差异。
本研究纳入了 187 名参与者，包括健康对照组（HC；n=50）或早期轻度认知障碍（EMCI；n=50）、晚期 MCI（LMCI；n=37）或 AD（n=50）。使用基于体素的形态计量学计算 NBM 体积，使用概率追踪法提取外侧和内侧 NBM 束的平均扩散系数（MD）。使用线性混合模型比较各组之间的 NBM 体积和束 MD 差异，分别控制年龄、性别和总颅内体积或对照掩模的 MD。还分析了 NBM 体积和束 MD 与执行功能、记忆、语言和视空间功能之间的相关性。
AD 患者的 NBM 体积最小，其次是 LMCI（p<0.0001），EMCI 与 HC 之间无差异。与其他所有组相比，AD 患者的两条束 MD 均最高（p<0.01）。与 HC 相比，两个 MCI 组的外侧束 MD 均较高（p<0.05）。与 HC 相比，LMCI 中的内侧束 MD 更高（p=0.008），但 EMCI 中无差异（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 的早期阶段最敏感，应被视为早期检测和干预的重要治疗靶点。
