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Cotinine Research Shows Alzheimer’s Promise

18th March 2015

In the search for treatments to prevent deterioration of the brain in aging and alzheimers, hopefully to delay or prevent cognitive loss, researchers have looked at chemical changes in the brain that they may block in order to protect this vital organ. One of these chemicals is acetyl-choline. The level and activity of this chemical is known to drop in alzheimers and it has important roles in controlling inflammation.

So researchers have already developed drugs like Galantamine, a chemical identified in daffodils, to boost acetyl-choline neuro-transmission in alzheimers, and the drug can be prescribed to delay cognitive decline in many countries. But it is not especially effective. Now scientists have realised that many of these chemical interventions are not very effective because these pathways are more complex than thought and there are a number that are involved. Also they have learned it's not just about the levels of a given compound but also how it is detected and responded to by cells. So they have started to look at combinations of drug to gain much more effect, a phenomenon known as 'synergy'. Researchers are excited by many possibilities, including polyphenols like curcuminoids (from turmeric) and the future looks promising in terms of combinations of pharmaceutical agents and natural compounds to greatly improve the treatment of these conditions.

One of the recent findings about acetyl-choline shows that a combination of cotinine, a naturally formed metabolite of nicotine, and a drug called Aricept, which prevents the degradation of acetyl choline and thereby increasing it's levels, is more effective than either alone (in animals). Cotinine boosts the levels of acetyl-choline but also the signalling of it through improved receptor functioning to protect brain cells from amyloid, and reduces the levels of this protein which is strongly implicated in neuro-degeneration.

Cotinine also boosts both learning and memory even in animals with normal acetyl-choline levels, therefore the researchers concluded it may be used in other conditions that could apply to humans. The problem with nicotine is in adolescents, where changes to inflammatory signalling can disrupt myelination, which allows long distance wiring to mature. After myelination is largely complete (in adults) the protective are thought to outweigh harms. Nicotine's benefits are potentially in reducing damage in adult, chronically aged or worn out brains rather than in youngsters. Therefore, the e-cig industry should ensure its products are aimed only at adults and smokers who wish to reduce or quit.

At this stage it isn't proven that benefits of nicotine outweigh risks, or the other way around, and it is not clear that vaping would deliver sufficient nicotine to change levels of the neuro-protective metabolite.