Cholinergic Changes in Aging and Alzheimer Disease: An [18F]-F-A-85380 Exploratory PET Study

The central cholinergic system undergoes changes during the physiological process of aging and the pathologic process of Alzheimer disease (AD). We aimed to analyze the impairment of cholinergic pathways by positron emission tomography using the [F]-F-A-85380 (FA85) tracer, which has a high affinity for nicotinic acetylcholine receptors (nAChRs). Aging was assessed by comparing young (n=10) and elderly (n=4) healthy subjects, and the pathologic process of AD was assessed by comparing elderly controls and age-matched AD patients (n=8). We measured an index of the nAChR density in the cortex and the hippocampus and the total number of FA85-binding sites by taking into account the volume changes. In AD, the nAChR density was preserved in both the cortex and hippocampus. The total estimated number of FA85-binding sites was decreased in the hippocampus despite the lack of a significant loss of volume, whereas the difference in the cortex did not withstand the adjustment for multiple comparisons despite a significant loss of volume. In contrast, in aging, the estimated number of FA85-binding sites was decreased in both the cortex and hippocampus with significant hippocampal atrophy. These findings suggest a preferential impairment of cholinergic pathways in the cortex during aging, whereas in AD, this damage predominated in the hippocampus with a potential compensatory cholinergic effect in the cortex.