Understanding and managing behavioural symptoms in Alzheimer's disease and related dementias: focus on rivastigmine.
Behavioural and psychological symptoms of dementia (BPSD) are among the most distressing manifestations of dementia and result in considerable social and economic costs. Practical, non-pharmacological approaches such as environmental and behavioural changes may provide some benefit for patients in managing mild BPSD. In addition, various pharmacological approaches to treatment have been employed, such as neuroleptics and atypical antipsychotics, which differ in neurochemical target and clinical effectiveness. Growing evidence suggests that the neurobiological basis of BPSD in Alzheimer's disease (AD) and related dementias is a loss of cholinergic neurones and a resultant decline in acetylcholine (ACh) in brain regions which regulate behavioural and emotional responses, such as the limbic system. This cholinergic deficit can be partly corrected by inhibiting cholinesterase enzymes (ChEs). Studies of ChE inhibitors have shown positive effects to improve or stabilise existing BPSD and delay the emergence of new behavioural symptoms. In placebo-controlled studies, donepezil has reported efficacy in non-institutionalised moderate to moderately severe patients over a period of 24 weeks, but has failed to demonstrate efficacy in mild to moderate AD and in institutionalised patients with severe disease. Galantamine has been shown to delay the onset of BPSD in mild to moderate AD patients in one placebo-controlled study, and improve BPSD in a similar study of patients with cerebrovascular disease or probable vascular dementia. Studies with rivastigmine have shown efficacy in placebo-controlled studies of mild to moderately severe AD and in patients with Lewy body variant AD. Institutionalised patients with severe disease also show symptomatic benefits in BPSD with rivastigmine, resulting in a reduction in concomitant psychoactive medication use. Symptom complexes responding to ChE inhibitors appear to differ - all agents improve apathy, depression and anxiety, while rivastigmine additionally improves hallucinations and delusions, possibility as a result of dual inhibition of acetylcholinesterase and butyrylcholinesterase. The presence of hallucinations has been shown to predict response to rivastigmine. Accumulating data from studies of ChE inhibitors suggest that early intervention and long-term treatment, in addition to providing cognitive benefits, improves BPSD and offers potential to enhance quality of life. Differences seen between the agents in terms of efficacy in BPSD, tolerability and safety profiles may be the result of differences in neuropharmacological profiles.
Robert
Philippe
P
Memory Centre UEC, Centre Hospitalier universitaire de Nice, France.
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000523:psychology* / Q000628:therapy*; D002219:Carbamates / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy; D018450:Disease Progression; D000077265:Donepezil; D005702:Galantamine / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D048448:Phenylcarbamates; D010830:Physostigmine / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D000068836:Rivastigmine; D013619:Tacrine / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D013619:Tacrine; D000077265:Donepezil; D010830:Physostigmine; D000109:Acetylcholine; D000068836:Rivastigmine