Volumetric Changes in Cerebellar Transverse Zones: Age and Sex Effects in Health and Neurological Disorders

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age-dependent volume reductions were observed across transverse zones, with the central zone (CZ; lobules VI and VII) exhibiting the steepest decline in both health and neurological disorders. This finding highlights the CZ's vulnerability to aging and its critical role in cognitive and emotional processing. We also found prominent sex differences in age-dependent volumetric changes. Males exhibited smaller total intracranial volume (TIV)-adjusted cerebellum volume and faster age-dependent volume reduction than females in both health and mild cognitive impairment (MCI), Alzheimer disease (AD), and Parkinson disease (PD). In contrast, females with schizophrenia (SZ) and cocaine use disorder (CUD) revealed faster age-dependent cerebellar volume reduction than males. Patients with MCI, AD, and PD experienced more pronounced atrophy in the posterior (PZ) and nodular (NZ) zones compared to age-matched healthy controls, while SZ patients were characterized by a more prominent reduction in CZ. In CUD, a non-significant volume decline was observed in all zones compared to the controls. Moreover, our framework for estimating cerebellum age revealed a notable difference in cerebellar aging between healthy individuals and neurological patients. Finally, we charted age-dependent changes in cerebellar volume in healthy individuals, focusing on transverse zones capturing the functional subdivisions. These findings underscore the potential of cerebellar volumetric analysis as a biomarker for early detection and monitoring of neurodegenerative and neuropsychiatric disorders. Our novel approach complements and enhances MRI-based analyses, providing essential insights into the pathogenesis of aging, neurodegeneration, and chronic neuropsychiatric conditions.