Jellinger Kurt A, Attems Johannes
Institute of Clinical Neurobiology, Vienna, Austria.
Dialogues Clin Neurosci. 2013 Mar;15(1):29-43. doi: 10.31887/DCNS.2013.15.1/kjellinger.
Cerebral aging is a complex and heterogenous process related to a large variety of molecular changes involving multiple neuronal networks, due to alterations of neurons (synapses, axons, dendrites, etc), particularly affecting strategically important regions, such as hippocampus and prefrontal areas. A substantial proportion of nondemented, cognitively unimpaired elderly subjects show at least mild to moderate, and rarely even severe, Alzheimer-related lesions, probably representing asymptomatic preclinical Alzheimer's disease, and/or mixed pathologies. While the substrate of resilience to cognitive decline in the presence of abundant pathologies has been unclear, recent research has strengthened the concept of cognitive or brain reserve, based on neuroplasticity or the ability of the brain to manage or counteract age-related changes or pathologies by reorganizing its structure, connections, and functions via complex molecular pathways and mechanisms that are becoming increasingly better understood. Part of neuroplasticity is adult neurogenesis in specific areas of the brain, in particular the hippocampal formation important for memory function, the decline of which is common even in "healthy" aging. To obtain further insights into the mechanisms of brain plasticity and adult neurogenesis, as the basis for prevention and potential therapeutic options, is a major challenge of modern neurosciences.
大脑老化是一个复杂且异质性的过程，与涉及多个神经网络的多种分子变化相关，这是由于神经元（突触、轴突、树突等）的改变所致，尤其会影响具有战略重要性的区域，如海马体和前额叶区域。相当一部分未患痴呆症、认知未受损的老年受试者至少表现出轻度至中度，甚至很少有严重的与阿尔茨海默病相关的病变，这可能代表无症状的临床前阿尔茨海默病和/或混合性病变。虽然在存在大量病变的情况下，认知衰退的恢复力基础尚不清楚，但最近的研究基于神经可塑性或大脑通过复杂分子途径和机制重组其结构、连接和功能来管理或抵消与年龄相关的变化或病变的能力，强化了认知或大脑储备的概念，而这些分子途径和机制正越来越被人们所理解。神经可塑性的一部分是大脑特定区域的成体神经发生，特别是对记忆功能很重要的海马结构，即使在“健康”衰老过程中，其衰退也很常见。深入了解大脑可塑性和成体神经发生的机制，作为预防和潜在治疗选择的基础，是现代神经科学的一项重大挑战。
