The cerebellum in aging and cognitive decline: longitudinal insights into function, structural networks, and neurodegeneration

The National Institute on Aging awarded Texas A&M University $640,059 on September 1, 2026, under the Aging Research program (CFDA 93.866) to investigate cerebellar changes in aging and cognitive decline through longitudinal neuroimaging and functional analysis.

The project examines how cerebellar structure, white matter circuits, and task-based functional activation change over time in older adults, with particular focus on individuals experiencing subjective cognitive decline—self-reported memory loss without objective impairment that predicts progression to mild cognitive impairment or Alzheimer's disease. The research characterizes cerebellar resting-state networks and structural changes across the aging lifespan, explores sex differences in cerebellar aging given higher female prevalence of Alzheimer's disease, and identifies potential early intervention targets and biomarkers of disease transition.

Performance occurs in College Station, Texas, with a period of performance from September 1, 2026, through May 31, 2031. The award is classified as a Project Grant, the standard assistance type for the NIA's aging research portfolio.

Abstract

Adults over the age of 65 represent one of the fastest growing demographics in the united states. As these individuals age, they face increasing challenges with respect to motor and cognitive function, which in turn impact quality of life and independence. The increased aging population also exacerbates concerns with respect to age- related neurodegenerative disease. Many aging individuals experience subjective cognitive decline (SCD), which is defined by self-reported declines in function, though objective performance is unimpaired. Relative to older adults without complaints (OA) these individuals are at higher risk for subsequent pathological decline as either mild cognitive impairment (MCI) or alzheimer's disease (ad). Given the increased risk for ad, SCD is exceptionally useful for the investigation of novel early intervention targets and markers of transition to disease, which are sorely needed. The cerebellum is one such target. The cerebellum is a processing powerhouse, with more neurons than the rest of the brain. In recent years, great strides have been made in providing a foundation of understanding cerebellar changes and how they impact behavioral changes across adulthood and in aging. This work has demonstrated changes in structure and resting state networks, and new preliminary data suggest that these patterns of change over time are more dramatic in those with lower cognitive function. Further, this work shows robust associations with behavior, and has demonstrated structural and network differences in males and females. The latter is particularly pertinent given that females have a higher prevalence of ad. Despite these advances, open questions remain with respect to changes in both cerebellar white matter circuits with the cortex and cerebellar task-based functional activation. Notably, SCD and relationships between cerebellar change and peripheral markers of neurodegeneration are unexplored, despite emerging interests in the cerebellum in this population. This work represents a key foundation for future work on cerebellar interventions. The objective of this proposal is to further explicate cerebellar aging with a focus on white matter and functional activation, while also exploring cerebellar changes in SCD. This proposal will take advantage of an existing longitudinal sample and will enrich this sample with individuals with SCD. 150 adults will complete two visits over 18-24 months. Aim 1 will quantify white matter and functional changes over time in OA. Aim 2 will focus on SCD, looking at lobular cerebellar volume, resting state networks, white matter, and function. This aim will quantify their changes over time, behavioral associations, and how these patterns differ from OA. Aim 3 will quantify SEX differences and relationships with SEX steroid hormones and cerebellar measures in SCD. Exploratory aim 4 will determine the degree to which cerebellar metrics relate to plasma markers of neurodegeneration, shown to be predictive of ad and disease course. This highly innovative work builds upon existing infrastructure and knowledge to have a significant impact on the understanding of the cerebellum in aging and in SCD. This work will clarify the degree to which the cerebellum may serve as a novel marker of disease progression, and as an intervention target.