Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer’s disease
Cummings JL, Schneider L, Tariot PN, Kershaw PR and Yuan W;
Commented by , 22 Oct 2004
Aim of the study
Assess the impact of the acetylcholinesterase inhibitor (AChEI) galantamine on the pattern and evolution of behavioral disturbances in patients with Alzheimer’s disease (AD) and caregiver distress related to the patients’ behavior.
Method
Sub-analysis of a pivotal 5-month double-blind study comparing galantamine to placebo in patients with probable mild to moderate AD, defined as MMSE 10-22 and ADAS-cog 18 or higher. Behavior was measured using the Neuropsychiatric Inventory (NPI) total score using 10 items, and the caregiver distress was measured using the NPI distress scale.
Data had been collected at baseline, then at 12 and 21 weeks postbaseline. Analysis was done using a step-down closed testing procedure, defined as a sequence of hypothesis in hierarchical order, such as comparing 24mg/day to placebo for a significance of 0.05, before doing 16mg/day vs. placebo. The NPI total score and the 10 individual items were analyzed.
Results
At baseline the mean MMSE was 18, the NPI mean total score was 12. Patients on placebo showed worsening of NPI item scores, whereas those on galantamine 16 or 24mg/day had no change, e.g. were stable behaviorally. In particular there was significant reduction in the emergence of aberrant motor behavior, apathy and disinhibition. Among the patients who were symptomatic at baseline, there was a reduction associated with galantamine for aberrant behavior, agitation/aggression and anxiety. There was a significant reduction in caregiver distress scores.
Professor Gauthier's comments
Behavioral and Psychological Symptoms of Dementia (BPDS) are being increasingly recognized as a major component of the burden for families and patients with AD. Agitation in particular has been associated with frontal lobe dysfunction in AD and has a marked impact on caregivers (ref. 1).
Although atypical neuroleptics have been proven useful in the management of some aspects of BPSD, including agitation, the safety of these drugs is under review (ref. 2). AChEI have been shown to have some effects on BPSD (ref. 3).
In a double-blind study comparing donepezil to placebo, improvement in NPI total score and of the three domains of apathy/indifference, anxiety and depression/dysphoria has been demonstrated, although there was no significant difference for rates of symptom emergence (ref. 4). The effects of memantine on agitation, either as a reduction if present at onset of treatment or as a delay in emergence in asymptomatic patients, has been demonstrated in more severe populations than the ones studied with AChEI so far (ref. 5).
These actions of AChEI and of memantine on BPSD need to be studied further as they may allow a significant improvement of the quality of life of patients with AD and their caregivers, and a reduction in the use of neuroleptics.
References
1. Senararong et al. Agitation in Alzheimer's disease is a manifestation of frontal lobe dysfunction. Dement Geriatr Cogn Disord 2004; 17: 14-20
2. Profenno & Tariot. Pharmacologic management of agitation in Alzheimer's disease. Dement Geriatr Cogn Disord 2004; 17: 65-77
3. Wynn & Cummings. Cholinesterase inhibitor therapies and neuropsychiatric manifestations of Alzheimer's disease. Dement Geriatr Cogn Disord 2004; 17: 100-108
4. Gauthier et al. Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. Int Psychogeriatrics 2002; 14: 389-404
5. Möbius et al. Memantine positively influences behavior in moderate to severe Alzheimer's disease. Neurobiology of Aging 2004; 25, S19