PDF(Pubmed)
Abstract：
Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer\'s disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.
摘要：
考虑到小脑在运动中的关键作用，认知，和情感操作，考虑到大脑功能随着年龄的增长而下降，小脑电路引起了科学界的注意。小脑在运动和认知操作的时间方面起着关键作用，包括空间导航等复杂任务。解剖学上,小脑通过突触间环与基底神经节相连,它接收来自大脑皮层几乎每个区域的输入。当前的主要假设是小脑建立内部模型，并通过与大脑皮层的多种相互作用促进自动行为，基底神经节和脊髓。随着年龄的增长，小脑经历结构和功能的变化，如在影响老年人的生理认知功能下降综合征（PCDS）中观察到的那样，参与了移动性虚弱和相关的认知障碍，功能保留的成年人，表现出缓慢和/或虚弱。小脑体积的减少伴随着衰老，至少与认知能力下降有关。在横断面研究中，小脑体积和年龄之间存在强烈的负相关，通常反映在运动任务中性能下降。尽管如此，尽管出现了明显的小脑萎缩,但预测运动时间评分在各年龄组仍保持稳定.小脑-额叶网络可以在处理速度中起重要作用，并且由于衰老而导致的小脑功能受损可以通过增加额叶活动来补偿，以优化老年人的处理速度。对于认知操作，默认模式网络(DMN)的功能连通性降低与较低的性能相关。神经影像学研究强调，小脑可能与阿尔茨海默病（AD）中发生的认知能力下降有关。独立于大脑皮层的贡献。AD中的灰质体积损失与正常老化中的灰质体积损失不同，最初发生在小脑后叶区域，与神经元有关，突触和β-淀粉样蛋白神经病理学。关于抑郁症,结构成像研究已经确定了抑郁症状与小脑灰质体积之间的关系。特别是,重度抑郁症（MDD）和较高的抑郁症状负担与小脑和小脑后部的灰质体积较小有关。Vermis,和后CrusI.从遗传/表观遗传学的角度来看，随着年龄的增长，小脑中突出的DNA甲基化变化都是低甲基化和高甲基化的形式，推测某些基因的表达增加/减少可能会影响运动协调。训练会影响运动技能，终身练习可能有助于老年小脑的结构维持，减少灰质体积的损失，因此有助于维持小脑储备。非侵入性小脑刺激技术越来越多地用于增强与运动相关的小脑功能，认知，和情感操作。它们可能会增强老年人的小脑储备。总之,在整个生命过程中，小脑会发生宏观和微观的变化，与大脑皮层和基底神经节的结构和功能连接发生变化。随着人口老龄化以及老龄化对生活质量的影响,专家小组认为，有一个巨大的需要，以澄清老化对小脑电路的影响如何改变特定的运动，认知，以及正常受试者和AD或MDD等脑部疾病的情感操作，为了预防症状或改善运动，认知，和情感症状。
