Aging, Neurodegenerative Disorders, and Cerebellum

Abstract

An important part of the central nervous system (CNS), the cerebellum is involved in motor control, learning, reflex adaptation, and cognition. Diminished cerebellar function results in the motor and cognitive impairment observed in patients with neurodegenerative disorders such as Alzheimer’s disease (AD), vascular dementia (VD), Parkinson’s disease (PD), Huntington’s disease (HD), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Friedreich’s ataxia (FRDA), and multiple sclerosis (MS), and even during the normal aging process. In most neurodegenerative disorders, impairment mainly occurs as a result of morphological changes over time, although during the early stages of some disorders such as AD, the cerebellum also serves a compensatory function. Biological aging is accompanied by changes in cerebellar circuits, which are predominantly involved in motor control. Despite decades of research, the functional contributions of the cerebellum and the underlying molecular mechanisms in aging and neurodegenerative disorders remain largely unknown. Therefore, this review will highlight the molecular and cellular events in the cerebellum that are disrupted during the process of aging and the development of neurodegenerative disorders. We believe that deeper insights into the pathophysiological mechanisms of the cerebellum during aging and the development of neurodegenerative disorders will be essential for the design of new effective strategies for neuroprotection and the alleviation of some neurodegenerative disorders.

Morphological changes in the cerebellum during aging: evidence from convolutional neural networks and shape analysis

“…Lesions in the posterior lobe of the cerebellum have been associated with the onset of cerebellar cognitive affective syndrome (CCAS), yet they do not significantly impact motor functions ( van Harskamp et al, 2005 ; Stoodley et al, 2016 ). In neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, the cerebellum is a critically impacted region, with morphological alterations over time due to sustained damage ( Iskusnykh et al, 2024 ). Consequently, examination of cerebellar regional changes in individuals who are cognitively normal during the aging process can provide valuable insights into the pathology of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s diseases.…”

A more objective PD diagnostic model: integrating texture feature markers of cerebellar gray matter and white matter through machine learning

“…The cerebellum, as a brain region associated with motor functions, may reveal microstructural alterations related to PD through changes in its texture features. Considering the cerebellum's role in coordination and fine motor control, investigating the texture features of gray and white matter greatly contributes to a profound understanding of PD's neurodegenerative process (Deuter et al, 2023 ; Iskusnykh et al, 2024 ; Saban et al, 2024 ). The purpose of this paper is not only to explore the potential of Parkinson's disease diagnosis using machine learning with cerebellar gray matter and white matter texture features, but also to find the most diagnostically valuable factors through model visualization.…”

Restoring cerebellar-dependent learning

“…Overall, this work has exciting therapeutic implications for Fragile X syndrome while also expanding our understanding of cerebellar long-term depression. Such knowledge may be crucial as the cerebellum has been implicated in several neurodevelopmental and aging disorders, yet specific treatments that target this structure are still lacking ( Wang et al, 2014 ; Arleo et al, 2024 ; Iskusnykh et al, 2024 ).…”