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

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.

Fig 1. STROBE diagram showing construction of the cohorts.

DLB, dementia with Lewy bodies; AChEIs, acetylcholinesterase inhibitors; LBD, Lewy body disease; DLB, dementia with Lewy body; CPFT, Cambridgeshire and Peterborough NHS Foundation Trust; ICD-10, World Health Organization International Statistical Classification of Diseases and Related Health Problems, 10th revision.

Fig 2. Kaplan-Meier survival curves of admissions and mortality in patients with dementia with Lewy bodies, by medication use.

Panels A, B and C present the recurrent events. P values are calculated from the log-rank test. AChEIs, acetylcholinesterase inhibitors.

Fig 3. Association of antidementia medication use with risk of admission, length of stay, and risk of death among patients with dementia with Lewy bodies.

Hazard ratios (HR), 95% confidence intervals (CI), and p values were estimated from Cox proportional hazards models. Coefficients, 95% confidence intervals (CI), and p values were estimated from linear regression. Adjusted HRs/coefficients were adjusted for age, sex, marital status, ethnicity, socio-economic status (Index of Multiple Deprivation), antipsychotic use, antidepressant use, cognitive status/score, physical comorbidity, anticholinergic burden, and global health performance. The blue lines show the unadjusted HRs/coefficients, the red lines show the adjusted ones, and the grey dotted line shows the cut-off for negative or positive associations (0 for coefficients and 1 for hazard ratios). AChEIs, acetylcholinesterase inhibitors.