Age-Related Decline in Anterior Cingulate and Medial Prefrontal Metabolism in Nonneurodegenerative Patients: An 18F-FDG PET Study

Abstract

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is widely used to evaluate patients with cognitive complaints, particularly to differentiate neurodegenerative disorders. However, memory impairment may arise from various nonneurodegenerative conditions, including metabolic, psychiatric, and nutritional factors. Age-related physiological changes in cerebral glucose metabolism may further complicate image interpretation and lead to potential diagnostic misclassification. This study aimed to investigate age-related regional metabolic changes in individuals undergoing brain FDG PET imaging without evidence of neurodegenerative disease.

A retrospective analysis was conducted on 77 patients (aged 19–89 years) who underwent brain FDG PET imaging between August 2023 and January 2025. All subjects had comprehensive clinical and neuropsychological evaluations, excluding neurodegenerative pathology. Quantitative analysis was performed using Cortex ID software on a dedicated workstation. Mean standardized uptake values were calculated for the anterior cingulate/medial prefrontal (ACC/MF), posterior cingulate/precuneus (PCC/PC), parietal, and temporal cortical regions. Correlation analyses were performed to assess the relationship between age and regional FDG uptake.

The study cohort consisted of 35 women (mean age: 62.48 ± 16.61 years) and 42 men (mean age: 69.92 ± 10.91 years). Increasing age was significantly associated with reduced FDG uptake in key frontal and cingulate regions, including the left PCC/PC cortex (R 2 = 0.05624, p = 0.0378), right ACC/MF cortex (R 2 = 0.05573, p = 0.0387), and left ACC/MF cortex (R 2 = 0.06828, p = 0.0217). However, the effect sizes were modest, indicating that age explained only a limited proportion of the variability in regional FDG uptake, while the scatter plots revealed considerable interindividual variability despite the overall age-related trend. No significant associations were observed in other cortical regions.

In individuals without neurodegenerative disease, advancing age is associated with a selective decline in glucose metabolism within the ACC and MF, with a weaker age-related effect in the left PCC/PC region. These findings support region-specific metabolic vulnerability during normal aging while highlighting substantial interindividual variability in cerebral glucose metabolism. Consequently, age-adjusted interpretation of FDG PET is essential. Borderline frontal hypometabolism should not be interpreted in isolation as evidence of frontotemporal dementia or frontal-variant Alzheimer's disease but should always be integrated with the patient's clinical presentation and neuropsychological assessment to minimize false-positive diagnoses.