Snyder_2025_Handb.Clin.Neurol_211_55

The role of the cholinergic system in the mediation of an entire complex hierarchy of interdependent cognitive functions, from the maintenance of arousal, to directed attention, to decision-making and problem-solving, and to new learning and memory, has been exceptionally well-studied over the past four decades. Disruption of cholinergic transmission has been implicated in the emergence of cognitive deficits for a range of neurodegenerative diseases, with disruption of cholinergic tone and neural circuitry in Alzheimer disease being the most common and most exhaustively explored of these diseases. Moreover, the use of pharmacologic probes in human studies to either upregulate or downregulate cholinergic tone in real time, and paired with appropriate and sensitive cognitive tasks, has led to a robust body of evidence. This evidence shows improvements vs impairments, respectively (e.g., enhanced vs degraded decision-making speed and efficiency), which confirm the complex and varied roles of cholinergic activity on cognitive functions in both health and disease states.