Lacalle-Aurioles María, Iturria-Medina Yasser
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada.
Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montreal, Canada.
Cereb Circ Cogn Behav. 2023 Jan 17;4:100158. doi: 10.1016/j.cccb.2023.100158. eCollection 2023.
Risk factors of late-onset Alzheimer's disease (AD) such as aging, type 2 diabetes, obesity, heart failure, and traumatic brain injury can facilitate the appearance of cognitive decline and dementia by triggering cerebrovascular pathology and neuroinflammation. White matter (WM) microstructure and function are especially vulnerable to these conditions. Microstructural WM changes, assessed with diffusion weighted magnetic resonance imaging, can already be detected at preclinical stages of AD, and in the presence of the aforementioned risk factors. Particularly, the limbic system and cortico-cortical association WM tracts, which myelinate late during brain development, degenerate at the earliest stages. The fornix, a C-shaped WM tract that originates from the hippocampus, is one of the limbic tracts that shows early microstructural changes. Fornix integrity is necessary for ensuring an intact executive function and memory performance. Thus, a better understanding of the mechanisms that cause fornix degeneration is critical in the development of therapeutic strategies aiming to prevent cognitive decline in populations at risk. In this literature review, i) we deepen the idea that partial loss of forniceal integrity is an early event in AD, ii) we describe the role that common risk factors of AD can play in the degeneration of the fornix, and iii) we discuss some potential cellular and physiological mechanisms of WM degeneration in the scenario of cerebrovascular disease and inflammation.
迟发性阿尔茨海默病（AD）的风险因素，如衰老、2型糖尿病、肥胖、心力衰竭和创伤性脑损伤，可通过引发脑血管病变和神经炎症，促使认知能力下降和痴呆的出现。白质（WM）的微观结构和功能尤其容易受到这些情况的影响。通过扩散加权磁共振成像评估的微观结构WM变化，在AD的临床前阶段以及存在上述风险因素时就已经可以检测到。特别是，在大脑发育后期才开始髓鞘化的边缘系统和皮质-皮质联合WM束，在最早阶段就会退化。穹窿是一条起源于海马体的C形WM束，是显示早期微观结构变化的边缘束之一。穹窿的完整性对于确保完整的执行功能和记忆表现是必要的。因此，更好地理解导致穹窿退化的机制对于制定旨在预防高危人群认知能力下降的治疗策略至关重要。在这篇文献综述中，i）我们深化了穹窿完整性部分丧失是AD早期事件的观点，ii）我们描述了AD常见风险因素在穹窿退化中可能发挥的作用，iii）我们讨论了在脑血管疾病和炎症情况下WM退化的一些潜在细胞和生理机制。
