Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults

We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n？=？24) and older adults (n？=？31).We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions.Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging.Normal aging is associated with declines in several cognitive domains, most notably episodic memory and executive functions (for reviews, see [1-4]). These cognitive deficits are associated with myriad brain changes, including structural and functional deterioration of prefrontal, basal ganglia, and medial temporal areas and their interconnections. However, establishing a link between these changes and cognitive decline in normal aging has proven surprisingly difficult [2,5].Alterations in two classic neurotransmitter systems have drawn considerable attention in cognitive aging: dopamine [6] and acetylcholine. For decades, acetylcholine (ACh) was thought of primarily as a memory-related neurotransmitter, but this view has recently been revised, with ACh now thought to play an equally if not more crucial role in executive functions (for reviews, see [7-9]). The integrity of cortical cholinergic inputs appears to be critical for modulating attention, by enhancing responsiveness to sensory inputs to facilitate cue detection and orienting [10] (for a review, see [9]). Cholinergic neuromodulation may also play an important role in executive functions by selectively enhancing task-relevant inpu