Q I have read that the long-term use by healthy people of cholinesterase inhibitors can reduce cholinergic neuron density in the brain. Is this true? It sounds illogical, as galantamine is known to do several things to boost cholinergic function. But is there any evidence of any negative outcome? Also, can galantamine be used with alpha-glycerylphosphorylcholine (alpha-GPC), a cholinergic agonist?

ERDAL, Bonita Springs, FL

A According to a recent review on galantamine, preclinical laboratory studies have shown that galantamine significantly increases nicotinic receptor density. This is thought to be associated with strengthened synaptic activity through long-term memory potentiation, which is related to cognitive function.1 We know of no studies indicating that long-term use can pose any problems.

Regarding the use of alpha-GPC, a multicenter, double-blind, placebo-controlled study showed the clinical usefulness and tolerability of CA [alpha-GPC, also known as choline alfoscerate] in the treatment of the cognitive symptoms of dementia disorders of the Alzheimer type.2

So alpha-GPC may be of benefit, and we know of no reason why it cannot be used along with galantamine. However, Durk Pearson and Sandy Shaw believe that simply taking adequate amounts of the nutrient choline, along with its cofactor, vitamin B5, is a satisfactory way to increase acetylcholine availability in the brain. The amounts they recommend are about 2 g for women and 3 g for men daily.


  1. Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimers disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging 2004; 21(7):453-78.
  2. De Jesus M, Moreno M. Cognitive improvement in mild to moderate Alzheimers dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther 2003;25(1):178-93.

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