Behavioural symptoms represent a challenge to physicians treating patients with Alzheimer’s disease (AD) and related dementias. While mild behavioural symptoms can be effectively managed using non-pharmacological approaches (e.g. environmental modification, attendance of support groups), the emergence of more severe, disruptive behaviours often calls for immediate clinical attention, and pharmacological intervention. At present, no single pharmacological treatment is currently approved for the management of behavioural symptoms of dementia.
In the nursing home setting, the use of neuroleptic or atypical antipsychotic medication is high, and treatment is often unmonitored. Side effects with these agents, such as extrapyramidal symptoms and tardive dyskinesia, when balanced against relatively low efficacy make their use in elderly, often frail patients debatable. Furthermore, in cognitively-impaired patients there is evidence of deleterious cognitive effects.1 Atypical antipsychotics generally offer a safer and more effective approach to treatment, although there are limited data examining the efficacy of these drugs in the elderly.
Cholinesterase (ChE) inhibitors are currently the standard therapeutic approach to the management of AD. Although these agents were initially developed as cognitive enhancers, additional beneficial effects on function and behavioural/neuropsychiatric symptoms have been demonstrated along the continuum of disease severity, including patients in the nursing home setting. Growing evidence suggests that cholinergic deficiency may underlie the occurrence of many behavioural symptoms in dementia. As such, ChE inhibitors offer a rational approach to chronic treatment, that targets the underlying neuropathophysiology.
Pharmacologically, ChE inhibitors differ substantially, which may have implications in terms of the behavioural efficacy observed. Donepezil and galantamine are selective inhibitors of acetylcholinesterase, the main enzyme responsible for the hydrolysis of acetylcholine (ACh) in the normal brain. Rivastigmine additionally inhibits butyrylcholinesterase (BuChE), which is widely distributed in limbic areas.2,3 The limbic system is known to be involved in the mediation and regulation of behavioural/emotional responses. Some data suggest that both donepezil4 and galantamine,5 in addition to inhibiting AChE, possess allosteric modulatory effects at the nicotinic ACh receptor, although the potential benefits of this additional property in terms of enhanced behavioural efficacy remains to be determined.
While treatment of the patient presenting with severe or disruptive behaviours with atypical antipsychotics offers an acute solution, consideration should also be given to the use of ChE inhibitors. These agents have demonstrated efficacy across a wide range of problem behaviours, and may offer a chronic, symptom-controlling approach to treatment.
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