Predictors of Response to Acetylcholinesterase Inhibitors: An Observational Case Register-Based Cohort Study

Background: Acetylcholinesterase inhibitors (AChEIs) are a key component of dementia care. Longitudinal cognitive change in patients before and after AChEI initiation has never been described previously, although individual responses have been described as heterogeneous. Predictors of such responses are not well established. This study describes longitudinal cognitive outcomes for patients who received AChEIs at the South London and Maudsley NHS Foundation Trust, UK during 2003 and 2010 in a routine clinical setting. Aims/ Objectives: The primary objective of the study was to describe trajectories of cognitive function, as measured by the MMSE in routine clinical practice in patients who had received AChEI, drawing on data before and after treatment initiation and comparing these slopes. The second objective was to investigate factors associated with cognitive response to AChEI treatment, defined as the difference in MMSE slopes before and after treatment initiation. Methods: A retrospective longitudinal study was constructed of data on 2,460 patients who received AChEIs with minimum of 1 MMSE score within 1 year before drug initiation and at least 1 MMSE score within 3 years after this. Longitudinal MMSE change was modelled using three-piece linear mixed models with the following segments: 0-12 months prior to AChEI initiation, 0-6 months and 6-36 months after initiation. Results: There was a significant improvement in the MMSE trajectory by 4.16 points per year in patients who received AChEIs during the 6 months after treatment compared with the 12 months before treatment. When stratified by MMSE score at AChEI initiation, lower MMSE was found to be associated with a stronger improvement in post- compared to pre-AChEI trajectory. MMSE score trajectories were similar over the 6-36 months after AChEI initiation compared with the 12 months before initiation.<br/>However, when stratified by baseline MMSE, patients with highest baseline MMSE had an exaggerated decline over the later period and those with lowest baseline scores had reduced slopes. Synthesis: This study found a significant improvement in the MMSE in patients who received AChEIs during the 6 months after treatment compared with the 12 months before treatment. When stratified by MMSE score at AChEI initiation, lower MMSE was found to be associated with a stronger improvement in post- compared to pre-AChEI trajectory. Heterogeneous response to AChEIs treatment found during first 6 months of AChEI drug initiation. Non-white ethnic groups who received AChEI treatment responded significantly better than patients from white population. Patients with Alzheimer’s disease recorded at some point responded better to AChEI than those without this diagnosis, and patients with vascular dementia recorded at any point responded less well than those without this diagnosis. Finally, considering pharmacotherapy, patients who received antipsychotics, gastrointestinal drugs and anti-platelet, fibrinolytic and anticoagulant agents at any point in follow-up were found to have a weaker response to AChEIs.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2013

Author dc:creator

• Perera, Gayan

Advisors dc:contributor.advisor

• Stewart, Robert James
• Breen, Gerome Daniel

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/f05e4b62-b389-457f-b86b-5d8c764e1517

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/f05e4b62-b389-457f-b86b-5d8c764e1517