APOE and Progression of AD–Combining Clinical and Research Data

Waleed Fawzi, Gayan Perera, Mizanur Khondoker, Tatjana Boitsova, Gerome Breen, Robert Stewart

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives
Cognitive decline in Alzheimer’s disease (AD) is inevitable, but the rate of this decline varies markedly between patients. Identifying a marker for the rate-of-decline can help in predicting prognosis and allocating resources and charting the course of care with patients and their families. Apolipoprotein E gene (APOE) is an important risk factor for late-onset AD and the presence of the genotype is the most significant genetic risk factor. However, establishing a role for APOE in predicting the rate of decline has proved elusive.

Methods
Patients with AD, living in the four boroughs of London covered by South London and Maudsley NHS Trust (SLAM), were identified from our research databases. The Case Register Interactive Search Tool (CRIS) (Stewart et al., 2009) , developed by the Biomedical Research Centre at SLAM was used to collect longitudinal MMSE data from anonymised clinical patient files. The patients selected had given consent for their clinical files to be accessed and provided samples for genetic analysis in the Dementia Case Register and the Addneuromed database at the Institute of Psychiatry. The search terms used on the CRIS clinical database were MMSE, mini-mental state examination, and AD. All clinical MMSE scores during the course of clinical care were collected and combined with data collected by the research teams. Decline slopes were charted and a linear mixed - effects model fit was used.

Results
69 overlapping patients were identified by the researchers. 23 patients had an APOE status of 23 or 33 and 46 patients were APOE 44 or 34. 569 MMSE assessments (average 8.24 / patient) were collected in total. The mean duration of follow up was 1280.67 days (3.5 years). APOE 34 and 44 patients showed significantly higher rates of decline. The findings remained significant after adjusting for the effect of sex, level of education and treatment with an acetyl choline esterase inhibitor.

Conclusions
This is a proof of concept study and our findings support the use of clinical databases for research purposes. Using data collected routinely for clinical care is cost effective and can produce statistically significant findings when large databases are used. This is even more significant for rare psychiatric conditions and where research funding is limited.
Original languageEnglish
Article numberN/A
Pages (from-to)719-720
Number of pages2
JournalNeurobiology of Aging
Volume35
Issue number3
DOIs
Publication statusPublished - 1 Mar 2014

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