Basal forebrain integrity and cognitive memory profile in healthy aging

Abstract

Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are assumed to contribute to age-associated impairment of explicit memory. Both neurotransmitters also modulate attention, working memory, and processing speed. To date, in vivo evidence linking structural age-related changes in these neuromodulatory systems to dysfunction within or across these cognitive domains remains scarce. Using a factor analytical approach in a cross-sectional study including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30 years) adults, we assessed the relationship between structural integrity-as measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain (major origin of cortical cholinergic projections), frontal white matter (FWM), and hippocampus to neuropsychological and psychosocial scores. Basal forebrain MTR and FWM changes correlated with a factor combining verbal learning and memory and working memory and, as indicated by measures of diffusion, were most likely due to vascular pathology. These findings suggest that frontal white matter integrity and cholinergic neuromodulation provide clues as to why age-related cognitive decline is often correlated across cognitive domains. IntroductionAge-related decline in learning and memory, often termed age-associated memory impairment (AAMI) (Crook et al., 1986), is a well-documented finding in healthy older adults (Balota et al., 2000;Cabeza et al., 2000;Craik, 1994;Salthouse, 2003), but the neurobiological correlates of this decline are still under debate. A consistent pattern of AAMI is a decrement in declarative memory (Tulving, 1985) most clearly apparent in impaired free recall and recollection (Buckner, 2004;Craik, 2006;Hedden and Gabrieli, 2004;Nilsson, 2003). Evidence from lesion studies in humans and animals indicates that

Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults

“…This lack of relationship was present despite clear reductions in SAI with age, which is consistent with our previous results in an independent sample (Young-Bernier et al, 2012; but see Oliviero et al, 2006; Degardin et al, 2011) and other evidence of a deterioration of the cholinergic system in normal aging (e.g., Mesulam et al, 2004; Duzel et al, 2010; Dumas and Newhouse, 2011; Grothe et al, 2012). …”

Efeito de um programa de treinamento da memória de trabalho em adultos idosos

“…Considerando-se que durante o envelhecimento normal a MT e a memória episódica estão dentre aquelas que sofrem maior declínio (Düzel et al, 2010) e que os resultados desse estudo mostraram o quanto é possível aprimorar a memória episódica, relacionada diretamente ao processamento dos subsistemas da MT, sugere-se que o TMT pode ser útil no contexto da neuropsicologia do envelhecimento. Considera-se possível então, auxiliar idosos na estimulação desses domínios cognitivos e possibilitar que profissionais na área da saúde prevejam ou contenham declínios nessas memórias, mantendo a independência funcional e qualidade de vida desses indiví-duos durante o envelhecimento.…”

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

“…When we performed an analysis across all individuals [52,53]; but see [54,55], SAI significantly predicted the memory factor score ( r  = −0.31, p  = 0.02), whereas it did not predict the executive function z score ( r  = −0.09, p  = 0.51; see Figure 1). The correlation between SAI and memory was modest in size ( r 2  = 10%), and when we examined the correlation separately within each age group it failed to obtain significance.…”