Alzheimer’s disease (AD) is a progressive neurodegenerative disorder accompanied by dementia as the symptomatic hallmark. More than 30 million people worldwide presently are diagnosed Alzheimer patients. It is expected that this number will increase to 40 million in 2020 and to 80 million in 2040.

AD is diagnosed by clinical symptoms that include cognitive, behavioural, functional and neuropsychiatric symptoms. It is still not clear how these symptoms relate to the underlying pathology of the disease. On the cellular level, the disease is characterised by extensive loss of synaptic connections and neurons, and by the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles. On the molecular level, AD is accompanied by an extensive loss of nicotinic acetylcholine receptors in cortical and subcortical regions, and subsequently by further disturbances in the cholinergic system. The non-cognitive clinical symptoms of AD, including depression, anxiety, hallucinations, and delusions, suggest that in addition to the cholinergic system, other neurotransmitter systems are also affected, at least on the functional level, including the glutamatergic, GABAergic, dopaminergic and serotonergic systems. Related to declines in dopamine release, parkinsonian symptoms are present in more than 30% of AD patients.

Presently, drug treatment of mild-to-moderate AD is based on cholinesterase inhibitors, such as donepezil (Aricept) and rivastigmine (Exelon), and on nicotinic enhancers, such as the APL galantamine (Reminyl, Razadyne). Cholinergic enhancement by these drugs improves learning, memory and attention and positively affects also non-cognitive symptoms.

Whereas donepezil and rivastigmine equally enhance both branches of cholinergic neurotransmission, i.e the muscarinic and nicotinic branch, galantamine predominantly improves nicotinic activity. In particular, by acting on presynaptic nicotinic receptors, it enhances the release of Glu, DA, 5HT and GABA, thereby providing positive modulation of these neurotransmitter systems.

Recent in-vitro and animal studies suggest that the action of galantamine on nicotinic receptors is neuroprotective and anti-apoptotic. Unfortunately, these effects are not easily observed when galantamine is administered to patients in the usual formulation as tablet, as only a very small fraction of the administered drug ever reaches the brain, and increased levels of unpleasant side effects prevent higher dosing. However, when Memogain instead of galantamine is administered, these neuroprotective and disease-modifying effects are much more pronounced, due to the much higher bioavailability of galantamine in the brain, and as demonstrated in several animal models of the disease.