Effectiveness of acetylcholinesterase inhibitors: diagnosis and severity as predictors of response in routine practice

Background Evidence from open label studies has indicated that patients with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) do better than those with other diagnoses, including Alzheimer's disease (AD). In addition, those with dementia of moderate severity do better than those with mild severity. Method Data collected for the monitoring of cholinesterase inhibitor prescribing in Oxfordshire over four years were supplemented with retrospective case notes inspection. 'Clinical response' was defined as improvement sufficient to merit continuation of therapy. A mini-mental state examination (MMSE) improvement of 2 or more points was defined as a 'cognitive response'. Results Medication was prescribed for 1322 patients and outcome data was available on 1250. Subsequently, 939 patients were reassessed after a mean of 120 days (SD 64.1). Medication was discontinued early by 311, mainly due to side effects. Of those who reached reassessment, 82% (771 of 939) were clinical responders and 37% (232 of 622) were cognitive responders. Overall, MMSE scores improved by +0.6 points [95% Confidence Intervals (CI) 0.3-0.9] and by +1.0 points (95% CI 0.71-3) in clinical responders; and deteriorated -1.5 points (95% CI -0.9--2.1) in clinical non-responders. A greater probability of clinical response was seen for DLB/PDD compared to AD patients [Odds Ratio (OR) = 2.28, 95% CI 1.074.89], and in men (OR = 1.51, 95% CI 1.02-2.23). A positive cognitive response was predicted by DLB/PDD compared to AD (OR = 2.07, 95% CI 1.16-3.70), moderate dementia compared to mild dementia (OR = 3.90, 95% CI 2.75-5.52), and by increasing age (OR 1.03 for each incremental year, 95% CI 1.01-1.06). Those with moderate dementia were not more likely to have a positive clinical response than those with mild dementia. Conclusions DLB/PDD patients were more likely to be both clinical and cognitive responders than those with AD. The finding that cognitive, but not clinical, response was more likely in those with moderate dementia than in those with mild dementia accords with the findings from randomised studies in the January 2006 revision of the NICE Appraisal Consultation Document. Copyright (c) 2006 John Wiley & Sons, Ltd.