Age-Related Changes in Caudate Glucose Metabolism: Insights from Normative Modeling Study in Healthy Subjects

Background: As the global population ages, the prevalence of neurodegenerative conditions, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies, and frontotemporal dementia, continues to rise. Understanding the impact of aging on striatal glucose metabolism is pivotal in identifying potential biomarkers for the early detection of these disorders. Methods: We investigated age-related changes in striatal glucose metabolism using both region of interest (ROI)-based and voxel-wise correlation analyses. Additionally, we employed a normative modeling approach to establish age-related metabolic trajectories and assess individual deviations from these normative patterns. In vivo cerebral glucose metabolism was quantified using a molecular neuroimaging technique, 18F-FDG PET. Results: Our results revealed significant negative correlations between age and glucose metabolism in the bilateral caudate. Furthermore, the normative modeling demonstrated a clear, progressive decline in caudate metabolism with advancing age, and the most pronounced reductions were observed in older individuals. Conclusions: These findings suggest that metabolic reductions in the caudate may serve as a sensitive biomarker for normal aging and offer valuable insights into the early stages of neurodegenerative diseases. Moreover, by establishing age-specific reference values for caudate glucose metabolism, the normative model provides a framework for detecting deviations from expected metabolic patterns, which may facilitate the early identification of metabolic alterations that could precede clinical symptoms of neurodegenerative processes.