The prevalence of
dementia is growing in developed countries where elderly patients are increasing in numbers. Neurotransmission modulation is one approach to the treatment of
dementia.
Cholinergic precursors,
anticholinesterases,
nicotine receptor agonists and
muscarinic M(2) receptor antagonists are agents that enhance
cholinergic neurotransmission and that depend on having some intact
cholinergic innervation to be effective in the treatment of
dementia. The
cholinergic precursor
choline alfoscerate may be emerging as a potential useful
drug in the treatment of
dementia, with few adverse effects. Of the
anticholinesterases,
donepezil, in addition to having a similar efficacy to
tacrine in mild-to-moderate
Alzheimer's disease (AD), appears to have major advantages; its use is associated with lower drop-out rates in clinical trials, a lower incidence of
cholinergic-like side effects and no liver toxicity.
Rivastigmine is efficacious in the treatment in
dementia with Lewy bodies, a condition in which the other
anticholinesterases have not been tested extensively to date.
Galantamine is an
anticholinesterase and also acts as an allosteric potentiating modulator at
nicotinic receptors to increase the release of
acetylcholine. Pooled data from clinical trials of patients with mild-to-moderate AD suggest that the benefits and safety profile of
galantamine are similar to those of the
anticholinesterases. Selective
nicotine receptor agonists are being developed that enhance cognitive performance without influencing autonomic and skeletal muscle function, but these have not yet entered clinical trial for
dementia. Unlike the
cholinergic enhancers, the M(1) receptor agonists do not depend upon intact
cholinergic nerves but on intact M(1) receptors for their action, which are mainly preserved in AD and
dementia with Lewy bodies. The M(1) receptor-selective agonists developed to date have shown limited efficacy in clinical trials and have a high incidence of side effects. A major recent advancement in the treatment of
dementia is
memantine, a non-competitive antagonist at
NMDA receptors.
Memantine is beneficial in the treatment of severe and moderate-to-severe AD and may also be of some benefit in the treatment of mild-to-moderate
vascular dementia. Drugs that modulate
5-HT,
somatostatin and noradrenergic neurotransmission are also being considered for the treatment of
dementia.