Volume 54, December 2023, 101311Author links open overlay panel, ,

Understanding behavior in aging has benefited greatly from cognitive neuroscience. Our foundational understanding of the brain in advanced age is based on what now amounts to several decades of work demonstrating differences in brain structure, network organization, and function. Earlier work in this field was focused primarily on the prefrontal cortex and hippocampus. More recent evidence has expanded our understanding of the aging brain to also implicate the cerebellum. Recent frameworks have suggested that the cerebellum may act as scaffolding for cortical function, and there is an emerging literature implicating the structure in Alzheimer’s disease. At this juncture, there is evidence highlighting the potential importance of the cerebellum in advanced age, though the field of study is relatively nascent. Here, we provide an overview of key findings in the literature as it stands now and highlight several key future directions for study with respect to the cerebellum in aging.

Section snippetsAn overview of the cerebellum in aging

The human cerebellum contributes to behavior across domains. From controlling smooth and coordinated movements 1, 2, to cognitive processing 3•, 4, and contributions to social cognition and affect [5], its contributions are wide. During typical function in the absence of disease, cerebellar computations are thought to primarily focus on forward and inverse internal models of behavior 6, 7, 8, 9. Given the consistent cytoarchitecture of the cerebellum, it has been suggested that the computations

Menopause, estrogen, and cerebellum

Females in later life experience more negative outcomes, as evidenced by both a higher incidence of AD and more severe falls 34, 35. There is an increasing recognition of the importance of women’s health broadly defined, and the necessity of understanding how the endocrine system and changes therein might impact brain and behavioral outcomes 36, 37. With respect to the cerebellum, this is an emerging area of particular interest. The cerebellum is dense with receptors for both estrogens and

The cerebellum in Parkinson’s disease

PD results from degeneration of dopaminergic cells in the midbrain [43]. While traditional approaches to investigating PD focused primarily on dopamine and the basal ganglia to understand parkinsonian deficits, Wu and Hallett [44] and Mirdamadi [45] argue pathology and compensatory mechanisms in the cerebellum also play a critical role. Alpha-synuclein Lewy bodies found in the Purkinje cells in the cerebellum [46] and iron accumulation in the dentate nuclei [47] result in alterations of white

The cerebellum in Alzheimer’s disease

Much like the broader literature on the cognitive neuroscience of aging, work on AD has not provided as much consideration of the cerebellum. However, new work in this area has highlighted the potential of the cerebellum in this field (for reviews see Refs. 49•, 5051]). While the cerebellum was long thought to be spared from AD due to a lessened presence of typical AD pathology, particularly senile plaque deposition and neurofibrillary tangles, emerging research shows changes in the cerebellum

Cerebellum as an intervention target

Given the purported scaffolding role that the cerebellum plays with respect to aging [33], and its connections with both motor and cognitive regions of the cortex 58, 59, the cerebellum may be a particularly effective target for remediation of deficits in advanced age. Brain stimulation is a particularly promising area in this regard. Indeed, recent work using cerebellar transcranial direct current stimulation in conjunction with fMRI demonstrated that cortical activation is altered relative to

Summary

The last several decades of research on cerebellar function have firmly established a role for this structure in nonmotor behavior. In the cognitive neuroscience of aging, research on the cerebellum remains a nascent area, but one with a great deal of potential. There is a strong foundation of work in this area demonstrating that cerebellar structure, network connectivity, and functional activation are all impacted in advanced age 16, 24, 25•, 31, 33•, and in many cases are related to

Declaration of Competing Interest

The authors declare no conflict of interest.

Acknowledgements

This work was supported in part by the National Institutes of Health (United States) R01AG064010 to JAB.

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