Christina Jensen-Dahm

Background: Opioid use is frequent among older people with dementia. Opioid use has been associated with excess mortality in the general population, but whether this also applies to older people with dementia is unknown. Objective: Investigate if new opioid use compared with no use was associated with excess mortality in older people with dementia. Methods: Matched cohort study using Danish nationwide registries including all residents (age 65+) diagnosed with dementia (including Alzheimer's disease) between 2008–2018. Exposure was defined as first opioid prescription after dementia diagnosis (1 year washout before). Persons exposed to opioids were matched with up to two unexposed persons on age and sex. Outcome was all-cause mortality within 180 days after exposure. Cox proportional hazards models compared rates of death and adjusted for potential confounders. Results: Forty-two percent (31,619/75,471) of older people with dementia initiated a prescription for an opioid after dementia diagnosis. 31,619 exposed persons were matched to 63,235 unexposed. Among the exposed, 8540 (27%) died within 180 days after initiating their first opioid prescription compared with 3803 (6.01%) of the unexposed, yielding a 5-fold excess mortality risk (adjusted Hazard ratio: 5.06 (95% CI, 4.86–5.29)). Transdermal fentanyl use was associated with an 8-fold excess mortality risk (8.26 (7.18–9.51)). Conclusions: Opioid use was associated with excess mortality, which may be due to the opioid, the indication or both. This observation calls for further research into the links between opioid use and excess mortality in elderly with dementia as it could have important implications for patient safety.

Introduction: People with dementia have an increased risk for infection‐related complications, which may be mitigated by common vaccinations. The aim was to investigate the association between influenza vaccination and the rates of all‐cause and influenza‐related hospitalizations and deaths among older adults with dementia. Methods: We followed all Danish residents with dementia aged 65 and above from September 1, 2002, to August 31, 2018. Dementia was defined from records in the Danish national registries (positive predictive value 85.8%). People with dementia were identified on September 1 of each year. On this date, vaccination status was also reset, and the status of covariates was assessed. We used proportional hazard Cox regression to compare rates of all‐cause hospitalization, hospitalization with a respiratory infection, hospitalization with influenza or pneumonia, and all‐cause mortality for vaccinated and unvaccinated. Results: Across the entire study period, we included 134,002 people with dementia. Rates of hospitalization were 9%–10% lower, and the mortality rate 9% lower, for vaccinated compared to unvaccinated among people with dementia. Discussion: Influenza vaccination was associated with lower rates of hospitalization and mortality among people with dementia. Further exploration of the preventive potential of influenza vaccination among people with dementia is important for shaping interventions in this vulnerable group.

Objective: To assess the association between cumulative use of anticholinergic bladder drugs and risk of all cause dementia compared with non-use and use of the β3 agonist bladder drug, mirabegron.Design: Danish nationwide active comparator study.Setting: National Danish registries, 1 January 2000 to 31 December 2022.Participants: 1 29 254 individuals with dementia were matched by age and sex to 646 270 controls without dementia, identified from a cohort of 2.26 million individuals aged 60-75 years between 2000 and 2022 with no previous dementia. Two separate nested case-control populations were studied: the general population and an active comparator population of 58 242 new users of bladder drugs (2198 developed dementia and were matched to 10 990 controls). Information on medication use was based on filled prescriptions and defined daily doses.Main outcome measures: Conditional logistic regression provided incidence rate ratios for associations between anticholinergic bladder drugs and dementia compared with non-use and mirabegron use adjusted for educational level, cardiovascular disease, diabetes, hypertension, dyslipidaemia, and Charlson Comorbidity Index.Results: Compared with non-use, ever use of anticholinergic bladder drugs was associated with an increased risk of dementia, with an incidence rate ratio of 1.44 (95% confidence interval (CI) 1.40 to 1.48). The incidence rate ratio increased with increasing cumulative drug use, from 1.31 (95% CI 1.27 to 1.36) for 1-90 defined daily doses to 1.68 (1.59 to 1.76) for >365 defined daily doses. Compared with non-use, all types of anticholinergic bladder drugs were associated with increased incidence rate ratios for dementia: tolterodine 1.43 (95% CI 1.38 to 1.49), solifenacin 1.37 (1.29 to 1.46), trospium 1.52 (1.37 to 1.67), and fesoterodine 1.48 (1.26 to 1.74). The increased risk of dementia with use of anticholinergic bladder drugs was not seen when compared directly with the use of the β3 agonist mirabegron (incidence rate ratio 0.82, 95% CI 0.74 to 0.92), irrespective of the type of anticholinergic drug.Conclusions: In this study, all types of anticholinergic bladder drugs were associated with an increased risk of dementia compared with non-use, but not when applying the active comparator of the β3 agonist bladder drug mirabegron. These findings highlight the relevance of using an active comparator. Future research should evaluate the risk of cognitive impairment and dementia for both types of bladder drugs.

Background and Objective: Psychotropic drug use is common in older adults, with off‐label use reported despite limited understanding of the safety outcomes compared to on‐label use. Incomplete recordings of treatment indications in the Danish National Prescription Register (DNPR) raise concerns about potential off‐label medication use, particularly among older adults. We, therefore, investigated the association between psychotropic prescriptions with non‐registered indications in DNPR and the 1‐year all‐cause mortality in older adults, including subgroups with any psychiatric disorders, depression, or dementia.Methods: Register‐based cohort study following all older adults (≥ 65) who redeemed a first‐time (since 1995) prescription of either antidepressants, antipsychotics, or benzodiazepine during 2006–2017. Redemption of a prescription with non‐registered indications in the DNPR was the exposure. The outcome, 1‐year all‐cause mortality was analyzed using Poisson regression, estimating incidence rate ratios with 95% confidence intervals, adjusting for socio‐demographics and clinical factors.Results: 32% of prescriptions filled by 202,067 individuals for antidepressants, 37% of 97,387 for antipsychotics, and 22% of 130,471 for benzodiazepines had non‐registered indications. No significant differences in mortality rates were found for antidepressants and antipsychotics with non‐registered indications, while higher mortality rates were associated with benzodiazepines, mitigated when excluding individuals receiving intravenous administrations representing end‐of‐life treatment. The results remained consistent in subgroup analyses in patients with any psychiatric disorders, depression, or dementia and further stratified analyses by sex and age.Conclusions: We found that while psychotropic prescriptions with non‐registered indications in DNPR were prevalent in older adults, they were not associated with excess mortality.

Background and Purpose: Previous studies have reported conflicting results regarding the association between influenza vaccination and dementia. This association was investigated in a nationwide register‐based cohort study.Methods: Using nationwide registries, dementia‐free adults aged ≥65 years in Denmark from 2002 to 2018 without previous influenza vaccinations were included. Poisson regression facilitated confounder‐adjusted comparisons of dementia rates for ever versus never vaccinated, number of vaccinations and within/after 5 years from first vaccination. Sensitivity analyses included stratification on age and sex.Results: Vaccination during follow‐up was associated with a slightly higher rate of dementia when adjusted for sociodemographic factors and comorbidities, both within and after the first 5 years from first vaccination (incidence rate ratio [IRR] 1.04; 95% confidence interval [CI] 1.03–1.05). The rate of dementia decreased with increasing number of vaccinations. The highest rate was amongst those with only one vaccination (IRR 1.14; 95% CI 1.12–1.17) and the rate of dementia was only decreased amongst those with six or more vaccinations (IRR 0.95; 95% CI 0.93–0.97). Applying the same models to control outcomes of hip fracture and cancer resulted in higher rates amongst vaccinated people of 6% and 7%, respectively. Vaccinated people also had a 10% higher mortality rate.Discussion: Our results do not support the case for a preventive effect of influenza vaccination on the risk of dementia in the general population, as reported by some previous studies. However, the higher dementia rate amongst vaccinated people found in this study is probably due to residual confounding, indicated by a higher rate for control outcomes and mortality.

Background: Opioids are used with increasing frequency. Elderly with dementia are prescribed opioids more frequent than elderly without. One possible explanation is that opioids may be used not only to treat pain but also behavioral symptoms. Objective: To test the hypothesis that strong opioid use, especially transdermal formulations, had increased, especially in elderly with dementia, in parallel with a decrease in antipsychotic use. Methods: Population-based cross-sectional study conducted using nationwide Danish registers with data on Denmark’s entire elderly population age ≥65 (2000: n = 802,106; 2015: n = 1,056,476). The registers were used to identify elderly with and without dementia and filled prescriptions for opioids and antipsychotics. Annual prevalence of opioid and antipsychotic use from 2000–2015 was calculated. Results: Prevalence of opioid use increased by 35% (24.2 to 32.5%) among elderly with dementia and by 13% among elderly without (14.9 to 16.8%) from 2000–2015. The disproportionate increase in opioid use among elderly with dementia was mainly driven by an increase in strong opioids (dementia: 11.7 to 23.1%; without dementia: 5.9 to 7.4%). Use of antipsychotics decreased during the same period (dementia: 31.3 to 19.3%; no dementia: 4.5 to 2.7%). Conclusion: From 2000–2015, use of opioids among the elderly increased with a disproportionately higher increase among elderly with dementia. The parallel decrease in the use of antipsychotics may suggest that opioids to some extent have replaced antipsychotics in managing behavioral symptoms, despite safety concerns and lack of evidence for effect of opioids. Future research should focus on potential risks associated with increased opioid use.