Preprint · Sep 16, 2024
Altered Cerebellar Activation Patterns in Alzheimer’s Disease and Mild Cognitive Impairment: An Activation Likelihood Estimation Meta-Analysis
By Bernard JA, Herrejon IA, Dempsey J et al.
The past decade has seen an increased interest in the cerebellum, particularly in non-motor behaviors. This has also included a growing interest in the cerebellum in aging, and age-related neurodegenerative disease. Emerging work across model systems and in humans has also implicated the cerebellum in Alzheimer’s Disease (AD) and in mild cognitive impairment (MCI). While the cerebellum is not seen as being central to the etiology of the disease, it is however recognized as being increasingly important, and most certainly not immune from disease-related pathology and atrophy. In cognitively normal older adults (OA), the cerebellum has been conceptualized as being critical scaffolding for cortical function. This scaffolding may extend to AD and MCI, wherein individual differences in cerebellar function and atrophy may relate to cognitive decline. With respect to functional imaging, there are differences in cerebellar activation in OA relative to young adults particularly during cognitive tasks. This supports the idea of functional scaffolding from the cerebellum. However, this is largely unexplored in AD and MCI, as this is a nascent literature. While there are very few studies focused on the cerebellum in AD and MCI at this stage, meta-analysis provides a powerful tool for expanding our knowledge of the cerebellum in neurodegenerative disease, and, in turn, for hypothesis generation. We took advantage of activation likelihood estimation (ALE) meta-analysis to investigate overlap in functional activation present in the existing literature. Our analysis included a total of 29 studies, representing data from 236 individuals with AD, 159 with MCI, and 382 OA. Across these studies, there is no significant overlap in cerebellar activation in AD, though this is present in MCI. Analyses of group differences also suggest that across studies, there are patterns indicative of both greater and reduced activation in AD/MCI relative to OA. Across all findings, overlap was primarily centered on Crus I and Lobule VI, the former of which has been implicated in AD. Together, these findings suggest that cerebellar function is negatively impacted in AD, and cerebellar resources may not be optimally recruited, which in turn may impact behavior and symptomatology.