The Cholinergic System in Aging

Abstract

A morphometric analysis of neuronal loss during normal aging was performed in the nucleus basalis Meynert complex of the basal forebrain (Nbm) (nucleus septi medialis, nucleus of Broca’s diagonal band, nucleus basalis) and the ciliary ganglion, a peripheral cholinergic structure, in patients free of neurological and psychiatric illness. As a basis for morphometric evaluation of the Nbm complex, a three-dimensional reconstruction of this complex structure was made. Neuronal counts in the Nbm complex and the ciliary ganglion remained stable up to the age of 60 or 50 years, respectively. After this age the number of neurons declined moderately in ciliary ganglion in all cases studied as well as in the Nbm complex in some cases (–20 and –25%, respectively, at about 90 years of age). In 3 out of 8 cases older than 60 years, neuronal counts in the Nbm complex were not reduced, so that no significant decline in neuronal number is apparent from the mean values of the 17 cases studied. No age-related changes were found in the neuronal distribution amongst the different subgroups of Nbm neurons using the alternative nomenclature of Mesulam et al. [J. comp. Neurol. 214: 170–197, 1983]. Our results provide no evidence that the cortical cholinergic projection system and peripheral cholinergic neurons might be especially vulnerable during normal aging. The severe degeneration of the cholinergic cortical projection system in SDAT is probably caused by mechanisms different from those acting during normal aging.

Neuronal Number and Size Are Preserved in the Nucleus basalis of Aged Rhesus Monkeys

“…In parallel to our findings in the NBM of monkeys, Bigl et al [25] found the number of cells in human NBM decreased from anterior to posterior re gions, and did not find an age-dependent change in cell number in any of the divisions of the NBM. In a detailed topographic analysis of morphometric changes in the human NBM, De Lacalle et al [22] did not find a relation ship between cell numbers in the anterior division of the NBM and age, although the mean cross-sectional area of NBM neurons in Ch4a was larger with increasing age.…”

“…In con cert with our observations in aged monkeys, several stud ies found stability of NBM neuronal numbers in humans with increasing age [25][26][27], However, an almost equal number of other studies in aged humans reported signifi cant decreases in NBM neuronal numbers [10,11,23,24], The reasons for these discrepancies are not clear, but sug gestions [60] that the inconsistencies between studies may be related to the age of subjects that were included in the studies, or the regions of the NBM that were sampled, may not be entirely accurate. For example, three studies [25][26][27] conducted in the anterior or intermediate aspects of the NBM found no cell loss in subjects between the ages of 25 and 90 years, whereas a similar study [10] did find cell loss in the anterior division of the NBM in subjects within this age range.…”

Effect of Potentiation of Cholinergic Tone by Pyridostigmine on the GH Response to GHRH in Elderly Men

“…Pyri dostigmine is an inhibitor of acetylcholines terase and thus it activates the cholinergic pathway leading to a suppression of somato statin release. In normal aging, the synthesis of brain acetylcholine is known to decline [11, 18-21], whereas choline acetyltransferase ac tivity and the density of muscarinic receptors do not change significantly [11][12][13][14], In the light of these observations, our present results may indicate that in elderly men there is a lower cholinergic inhibitory tone in the con trol of hypothalamic somatostatin release. In fact, when unmasked by pyridostigmine, cho linergic neurotransmission appeared to be markedly reduced in elderly subjects.…”

“…However, differences between younger and older sub jects in the metabolic clearance rate of the drug are unlikely, because pyridostigmine is readily absorbed from the gastrointestinal tract [7], and all subjects were in good nutri tional condition. Furthermore, studies of brain cholinesterase do not show significant changes in this enzymatic activity in normal aging [11][12][13][14].…”

Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys

“…Studies in the primate basal forebrain complex have alternately reported a loss of cholinergic neurons (e.g., Stroessner-Johnson et al, 1992) or no change (Bigl et al, 1987;Voytko et al, 1995;Gilmor et al, 1999), but few used stereological methods of quantification or assessed cell number independent of a potential loss of cholinergic phenotype. In one study of note, Smith et al (1999) found that, although a substantial percentage of cholinergic neurons in the aged monkey Ch4i (a neocortically projecting division of the nucleus basalis of Meynert) are no longer immunoreactive for the p75 receptor, overall neuron number fails to differ as a function of age, and NGF treatment successfully rescues the loss of p75-positive phenotype.…”