Antipsychotics and cognitive decline in Alzheimer's disease: the LASER-Alzheimer's disease longitudinal study

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Abstract
Objective: To investigate in a longitudinal cohort of people with Alzheimer’s disease whether taking antipsychotics is associated with more rapid cognitive deterioration. Method: From a sample of 224 people with Alzheimer’s disease recruited as epidemiologically representative, those taking antipsychotic drugs for more than 6 months were compared with those who were not, in terms of change in three measures of cognition. The effects of potential mediators and confounders (demographic factors, neuropsychiatric symptoms, cognitive severity and cholinesterase inhibitors) were also examined. Results: No significant difference was observed in cognitive decline between those taking antipsychotics (atypical or any) and others on any measure of cognition. The only predictor of more cognitive decline was greater baseline cognitive severity (B = 3.3, 95% confidence interval 0.6 to 6.1, t = 2.4, p<0.05). Although mortality was higher in those treated with antipsychotics, this reflected their greater age and severity of dementia. The results were the same when the whole cohort was included rather than the select group with potential to change who had been taking antipsychotics continuously. Conclusions: In this, the first cohort study investigating the effects of atypical antipsychotics on cognitive outcome in Alzheimer’s disease, those taking antipsychotics were no more likely to decline cognitively over 6 months. Although clinicians should remain cautious when prescribing antipsychotic drugs to people with Alzheimer’s disease, any increase in cognitive deterioration is not of the magnitude previously reported. There is a need for cohort studies that follow up patients from first prescription in clinical practice for a period of months rather than weeks to determine “real-life” risks and benefits.