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Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study

Research output: Contribution to journalArticlepeer-review

Shanquan Chen, Annabel Price, Rudolf Cardinal, Sinéad Moylett, Anne D. Kershenbaum, James FitzGerald, Christoph Mueller, Robert Stewart, John T. O'Brien

Original languageEnglish
JournalPLoS Medicine
DOIs
Accepted/In press14 Oct 2022
Published6 Dec 2022

Documents

  • journal.pmed.1004124

    journal.pmed.1004124.pdf, 1.57 MB, application/pdf

    Uploaded date:08 Dec 2022

    Version:Final published version

    Licence:CC BY

King's Authors

Abstract

Background
Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality
than Alzheimer’s disease (AD). The reasons for this are unclear, but antidementia drugs
(including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit
people with DLB and might improve outcomes. We investigated whether AChEIs and/or
memantine were associated with reduced hospital admissions and mortality.
Methods and findings
We performed a retrospective cohort study of those diagnosed with DLB between 1 January
2005 and 31 December 2019, using data from electronic clinical records of secondary care
mental health services in Cambridgeshire and Peterborough NHS Foundation Trust
(CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as
linked records from national Hospital Episode Statistics (HES) data. Eligible patients were
those who started AChEIs or memantine within 3 months of their diagnosis (cases) and
those who never used AChEIs or memantine (controls). Outcomes included admission,
length of stay, and mortality. Cox proportional hazard and linear regression models were
used.
Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only,
and 273 took both AChEIs and memantine. The cohorts were followed up for an average of
896 days, 981 days, and 1,004 days, respectively. There were no significant differences in
the cohorts’ baseline characteristics, except for socioeconomic status that was lower in
patients who never took AChEIs or memantine (χ2 = 23.34, P = 0.003). After controlling for
confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic
status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity,
anticholinergic burden, and global health performance, compared with patients who never
took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly
lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02;
adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs
or both AChEIs and memantine had significantly shorter periods of unplanned hospital
admission for physical disorders (adjusted coefficient −13.48, 95% CI = [−26.87, −0.09], P =
0.049; adjusted coefficient −14.21, 95% CI = [−24.58, −3.85], P = 0.007, respectively), but
no difference in length of stay for planned admissions for physical disorders, or for admissions
for mental health disorders. No significant additional associations of memantine on
admission, length of stay, and mortality were found (all P > 0.05). The main limitation was
that this was a naturalistic study and possible confounds cannot be fully controlled, and
there may be selection bias resulting from nonrandom prescription behaviour in clinical practice.
However, we mimicked the intention-to-treat design of clinical trials, and the majority of
baseline characters were balanced between cohorts. In addition, our series of sensitivity
analyses confirmed the consistency of our results.
Conclusion
In this study, we observed that use of AChEIs with or without memantine in DLB was associated
with shorter duration of hospital admissions and decreased risk of mortality. Although
our study was naturalistic, it supports further the use of AChEIs in DLB.

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