Cholinergic neurotransmission in the anterior cingulate cortex is associated with cognitive performance in healthy older adults: Baseline characteristics of the Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) trial

Aging is associated with dysfunction in the cholinergic system, including degeneration of basal forebrain cholinergic terminals that innervate the cortex, which directly contributes to age- and disease-related cognitive decline. In this study, we used [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) imaging to assess the effect of age on cholinergic terminal integrity in predefined regions of interest and its relationship to cognitive performance in healthy older adults who underwent neuropsychological assessment and FEOBV PET brain imaging. Our results showed age-related reductions in FEOBV binding, particularly in the anterior cingulate cortex-our primary region of interest-as well as in the striatum, posterior cingulate cortex, and primary auditory cortex. Notably, FEOBV binding in the anterior cingulate cortex was positively correlated with cognitive performance on the NIH EXAMINER Executive Composite Score. These findings suggest that [18F]FEOBV PET imaging can be used as a reliable biomarker to assess cholinergic changes in the human brain and indicate that preserving the cholinergic integrity of the basal forebrain may help maintain cognitive function and protect against age-related cognitive decline.