Cognitive symptoms

The cholinergic theory of dementia in Alzheimer's disease proposes that much of the cognitive decline is due to loss of the cholinergic innervation of the brain. Current treatments for the cognitive symptoms of Alzheimer's disease are cholinesterase inhibitors. It is proposed that these drugs improve cognition by making the remaining cholinergic fibres more effective.

The three acetylcholinesterase (AChE) inhibitors donepezil, galantamine and rivastigmine as monotherapies are recommended as options for managing mild to moderate Alzheimer's disease.

Memantine monotherapy is recommended as an option for managing Alzheimer's disease for people with:

• moderate Alzheimer's disease who are intolerant of or have a contraindication to AChE inhibitors
• or severe Alzheimer's disease

For people with an established diagnosis of Alzheimer's disease who are already taking an AChE inhibitor:

• memantine should be considered in addition to an AChE inhibitor if they have moderate disease
• memantine should be offered in addition to an AChE inhibitor if they have severe disease

Acute cognitive decline due to delerium superimposed on the dementia is common; in this case the underlying condition should be treated.

Notes:

• memantine
  • is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, represents the first member of a new class of medications showing clinical benefit and good tolerability in Alzheimer's disease
    • N-methyl-D-aspartate receptors (NMDAR), ionotropic glutamate receptor, are essential for processes like learning and memory
      • excessive activation of NMDARs has been associated with neuronal loss
      • memantine is an antagonist of extrasynaptic NMDAR - has been demonstrated that memantine preferentially prevents the excessive continuous extrasynaptic NMDAR disease activation and therefore prevents neuronal cell death induced by excitotoxicity without disrupting physiological synaptic activity

Reference:

1. Drug and Therapeutics Bulletin (2003); 41 (10):73-6.
2. NICE (November 2006).Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer's disease
3. NICE (June 2018). Dementia: assessment, management and support for people living with dementia and their carers