Aging-Related Hypometabolism in the Anterior Cingulate Cortex of Cognitively Intact, Amyloid-Negative Seniors at Rest Mediates the Relationship between Age and Executive Function but Not Memory.

The anterior cingulate cortex (ACC) shows the most aging-related brain metabolic dysfunction that correlates with decreasing executive processing in otherwise healthy, cognitively intact volunteers. Here, data from ADNI are used to elucidate potential pathophysiological mechanisms involved in cognitive aging, that is, age-related decline in cognitive performance in the absence of known neurodegenerative disease. Amyloid-negative volunteers showed statistically significant mediation of ACC metabolism in the relationship between age and verbal fluency. A nonlinguistic task of executive function, Trails B, showed also negative correlation between performance and age, albeit weaker, but was not significant in the mediation analysis. Recall of story items, minimizing attentional demands compared with learning of word lists, did not correlate with age. ADNI subjects selected for low vascular risks also showed correlation between age and declining ACC metabolism. In the whole-brain amyloid-negative subset, ACC amyloid was not correlated with age. As expected, the metabolism in an arbitrary region such as motor cortex that was not expected to decline with cognitive aging showed no correlation with age or ACC metabolism suggesting regional specificity. These findings motivate the search for the pathophysiology of aging-related ACC dysfunction to prevent, diagnose, and treat the decline in executive function associated with cognitive aging.