Although most dementia cases (~65%) are associated with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), dementia with Parkinson’s disease (PDD), vascular dementia (VaD) and ‘mixed’ dementia account for a large number of cases. Symptomatically, these different dementia syndromes are associated with variable combinations of cognitive and functional impairment, and emergent behavioural and neuropsychiatric features. DLB is often characterised by fluctuating cognitive impairment and the occurrence of visual hallucinations, delusions, sleep disturbances and depression.1 Behavioural symptoms are also common in PDD, particularly visual hallucinations, nightmares, delusions, anxiety and apathy.2 Similarly, VaD and ‘mixed’ dementia are often accompanied by excessive changes in behaviour and personality.3 As in AD, the behavioural aspects of these disorders are extremely distressing for the caregiver, and may precipitate institutionalisation of the patient.
Although it is widely known that a cholinergic deficit underlies AD, evidence is emerging that compromised cholinergic function may also be involved in non-AD dementias. In DLB, levels of choline acetyltransferase (ChAT) are more depleted than in AD, and there is a profound loss and disruption of cholinergic projections. In PDD, there is a similar loss of cholinergic function, caused by degeneration of cholinergic nuclei in the brainstem and consequent loss of innervation to the occipital cortex and thalamus. In VaD, loss of cholinergic neurones, reduced numbers of muscarinic acetylcholine receptors and depleted levels of ChAT are commonly observed. Thus, there appears to be a strong rationale for the use of cholinergic enhancing agents in these disorders.4
In DLB, one randomised, placebo-controlled study has been completed (using rivastigmine) which showed a particularly beneficial effect on behavioural symptoms such as hallucinations, delusions, apathy and depression.5 In PDD, results from small, open studies have been promising, with one study using rivastigmine reporting improvements in hallucinations, sleep disturbances and caregiver distress.6 In VaD, a few large, placebo-controlled studies have been completed, and a number are currently ongoing. In a 6-month study in patients with AD and cerebrovascular disease or probable VaD, galantamine showed a significant benefit on the neuropsychiatric inventory (NPI), compared with placebo. Apathy and anxiety symptoms significantly improved from baseline on galantamine, although worsening of aberrant motor behaviour occurred in both groups.7 An open study with rivastigmine in patients with subcortical VaD indicated sustained efficacy up to 22 months on the NPI.8
While initial results look positive, future research in these disorders will undoubtedly serve to provide a clearer and more defined role for the use of ChE inhibitors to control problem behaviours in these disorders.
Back to S113 Behavioral Symptoms in Dementia: Challenging the Current Treatment Paridigm
Back to Satellite Symposia
Back to The Eleventh International Congress