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

Abstract

BackgroundThe deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging.MethodsWe 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).ResultsWe 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.ConclusionIndividual 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.

A meta-analysis of the effects of aging on motor cortex neurophysiology assessed by transcranial magnetic stimulation

“…Refer to Fig. 4 for the forest plot of the for the SAI analysis comparing older versus young adults (Degardin et al , 2011, Young-Bernier et al , 2012b, Young-Bernier et al , 2014, Young-Bernier et al , 2015). …”

“…More recently, Degardin et al demonstrated a slightly greater SAI in older compared to young adults; however, this result was was not statistically significant (Degardin et al , 2011). However, Young-Bernier’s group have shown that older adults have a selective decrease in MEP inhibition at an ISI of 20ms (Young-Bernier et al , 2012a, Young-Bernier et al , 2012b, Young-Bernier et al , 2014, Young-Bernier et al , 2015), suggesting a decrease in central cholinergic function in normal aging. Congruent with these findings, our analysis revealed significantly decreased MEP inhibition in older compared to younger adults.…”

“…Five of the 31 studies (Rossini et al , 1992, Fujiyama et al , 2011, Opie et al , 2014, Young-Bernier et al , 2014, Young-Bernier et al , 2015) did not explicitly state the handedness of the participants. A total of three studies included both right and left-handed participants (Matsunaga et al , 1998, Fujiyama et al , 2009, Young-Bernier et al , 2012b). …”

TMS and drugs revisited 2014

“…SAI increases with the intensity of the conditioning stimulus (Fischer and Orth, 2011). SAI decreases with normal aging (Young-Bernier et al, 2012a, Young-Bernier et al, 2012b and in neurodegenerative disorders of the central cholinergic system, such as Alzheimer's disease (Di Lazzaro et al, 2005aNardone et al, 2008Nardone et al, , 2011 and Parkinson's disease (Celebi et al, 2012;Nardone et al, 2013;Rochester et al, 2012;Yarnall et al, 2013). Accordingly, it was proposed that SAI is a physiological marker of the integrity and excitability of central cholinergic pathways.…”

Mechanisms of Cognitive Aging in the HIV-Positive Adult

“…Neuronal loss, loss of connectivity, and alterations in task-related activation patterns within the brain all contribute to outward symptoms of cognitive aging [44-47], particularly the dopaminergic and cholinergic neurotransmitter systems. The functioning of the cholinergic and dopaminergic systems, and cognitive performance are affected by advancing age [48] which may lead to effects on cognitive abilities such as attention and executive control.…”