Keywords: Alzheimers disease; dementia; cholinesterase inhibitor; tacrine; donepezil;
rivastigmine; galantamineAuthor affiliations: University
of Manchester, Education and Teaching Centre, Wythenshawe
Hospital, Manchester, UKAddress for correspondence: Prof Alistair Burns, University of Manchester,Education and Teaching Centre, Wythenshawe Hospital, Manchester, M239LT, UK(e-mail: a_burns@man.ac.uk)lzheimers disease is the commonest cause ofdementia and describes a clinical syndrome made up ofthree domains. First, a neuropsychological domainencompassing those deficits of cognitive function such
asamnesia (memory loss), aphasia (language disturbance),apraxia (the inability to carry out motor tasks despiteintact motor functions), and agnosia (the inability
to rec-ognize people or objects despite intact sensory func-tions). Second, a group of psychiatric symptoms andbehavioral disturbances, which have been termed
neu-ropsychiatric features,1 noncognitive phenomena, orbehavioral and psychological symptoms of dementia(BPSD).2 These
consist of psychiatric symptoms (such asdelusions, hallucinations, depression, paranoid
ideas, andmisidentifications) and behavioral disturbances (such
asaggression, wandering, and sexual disinhibitions). Third,problems with activities of daily living (ADL), whichinclude instrumental ADL in the early stages of demen-tia when the person is unable to carry out complex tasks,such as shopping, driving, and using the telephone, andbasic ADL in the later stages of dementia, when
a personis unable to go to the toilet or feed, dress, and
wash them-selves.Causes of dementiaThe relative frequency of causes of dementia varydepending on the population under study. Alzheimersdisease is probably the commonest form (about 50%),followed by vascular dementia (about 25%) and demen-tia with Lewy bodies (about 20%), with the other
5%being made up of reversible dementias and rarer formsP h a r m a c o l o g i c a l a s p e c t s3 5Treatment of cognitive impairment
inAlzheimers diseaseAlistair Burns, MD, FRCP, FRCPsychAIn Alzheimers disease, cognition
now responds to severaldrugs. Anticholinesterases target
the acetylcholine deficit.In mild-to-moderate Alzheimers
disease, they all providesignificant benefit versus placebo on the AlzheimersDisease Assessment ScheduleCognitive
Section (ADAS-Cog). Side effects, in 5% to 15%
of cases, include nausea,vomiting, diarrhea, anorexia, and
dizziness. Tacrine, theleading anticholinesterase, caused
frequent hepatic enzymeelevation and was withdrawn; once-daily
donepezil sparesthe liver and improves global measures of
change in severedementia; rivastigmine is indicated
in comorbid vasculardisease; while galantamine modulates
the cerebral nico-tinic acetylcholine receptors that
potentiate the responseto acetylcholine. Alternative agents
include the N-methyl-D-aspartate (NMDA) receptor antagonist,
memantine,licensed in Europe for moderately severe to severeAlzheimers disease; it acts
on a different neurotransmit-ter system present in 70% of neurons,
protecting againstpathologic glutamergic activation
while preserving oreven restoring physiologic glutamergic
activation. Theclinicians armamentarium in
AD has never been greater.Dialogues Clin Neurosci.
2003;5:35-43.