Managing cognitive dysfunction through the continuum of Alzheimer's disease: role of pharmacotherapy

It has been shown that, during several years preceding the diagnosis of Alzheimer's disease there is a gradual cognitive decline with a continuum between the pre-dementia stage (still known as the prodromal stage but now included within the general concept of mild cognitive impairment [MCI]) and the other stages of the disease. In MCI, the use of cholinesterase inhibitors (ChEIs) is not associated with any delay in the onset of Alzheimer's disease or dementia. During the dementia stages, the three ChEIs (donepezil, galantamine and rivastigmine) are efficacious for mild to moderate Alzheimer's disease; therefore, monotherapy with a ChEI can be envisaged as initial treatment. Confirmation of the efficacy of ChEIs in the mild dementia stage is essentially based on the results from a single, randomized study carried out specifically among patients at this stage of severity. Memantine can represent an alternative to ChEIs in the moderate stage of Alzheimer's disease. At the severe stage of the disease, memantine and donepezil are currently indicated. Indeed, memantine has been approved by numerous drug regulatory agencies for use in severe stages of the disease, whereas donepezil has only been approved by the US FDA. There is currently insufficient evidence for recommending combination therapy in Alzheimer's disease.