Authors: Jensen-Dahm, Christina | Christensen, Ane Nørgaard | Gasse, Christiane | Waldemar, Gunhild
Article Type: Research Article
Abstract: 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. Show more
Keywords: Antipsychotic, behavioral symptoms, dementia, drug use, opioid, pain
DOI: 10.3233/JAD-190787
Citation: Journal of Alzheimer's Disease, vol. 73, no. 1, pp. 259-267, 2020
Authors: Jensen-Dahm, Christina | Zakarias, Johanne Købstrup | Gasse, Christiane | Waldemar, Gunhild
Article Type: Research Article
Abstract: Background: We recently reported frequent use of opioids among elderly with dementia. Discrepancies in clinical practice may in part explain the higher use of opioids in elderly with dementia, which geographical variation may be able to clarify. Objective: To investigate geographical variation in opioid use in elderly with dementia compared to elderly without dementia. Methods: Register-based cross-sectional study in the entire elderly (≥65 years) population of Denmark in 2015. Data included place of residence, prescriptions, and discharge diagnoses from hospital contacts. Prevalence of opioid use among elderly with (n = 36,014) and without dementia (n = 1,011,787) was compared nationwide across the …five Danish regions using logistic regression analysis and for the 98 municipalities using age and sex standardization. Results: 32.5% of elderly with dementia and 16.9% without were treated with an opioid in 2015. For home-living elderly with dementia, there was a 4-fold difference in opioid use (9.4 to 36.8%) between municipalities compared to a 1.6-fold (12.7 to 20.2%) difference for elderly without. In nursing home residents there was a 2-fold difference (dementia: 26.5 to 55.2%; no dementia: 31.8 to 60.4%). Differences between the five regions were minor. Conclusion: Opioid use in elderly with dementia was frequent and almost twice as high compared to elderly without dementia, which may challenge patient safety. The pronounced geographical variations at municipality level, particularly among elderly with dementia, indicate differences in the approach to treatment of chronic pain in primary care. Our study suggests that more guidance on treatment of pain in elderly with dementia is needed. Show more
Keywords: Analgesics, dementia, elderly, opioid, pain
DOI: 10.3233/JAD-190413
Citation: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1209-1216, 2019
Authors: Kristensen, Rachel Underlien | Jensen-Dahm, Christina | Gasse, Christiane | Waldemar, Gunhild
Article Type: Research Article
Abstract: Background: Studies have shown declining use of potentially inappropriate medication (PIM), medication where risks associated with use outweigh potential benefits in older people. However, the trend in people with dementia remains unknown. Objective: To test the hypothesis that the use of PIM has decreased in people with dementia in line with the declining use in the general older population. Methods: Repeated cross-sectional register-based study of the entire Danish population aged ≥65 years (2000: N = 802,106; 2015: N = 1,056,476). PIM was identified using the Danish “Red-yellow-green list”. Changes in the use of PIM were examined by calculating the annual prevalence of filling prescriptions …for at least one PIM in older people with and without dementia. Characteristics of the study population were examined annually including comorbidity. Results: From 2000 to 2015, the prevalence of PIM use decreased from 54.7%to 43.5%in people with dementia and from 39.5%to 28.8%in people without dementia; the decrease was significant across all age groups and remained so in a sensitivity analysis where antipsychotics were removed. During the same period, comorbidity scores increased in people with and without dementia. Conclusion: The declining use of PIM in people with dementia from 2000 to 2015 parallels the trend in the general older population. The use of PIM decreased despite increasing levels of comorbidity and was not solely attributable to the decreasing use of antipsychotics in people with dementia. However, PIM use remained more widespread in people with dementia who may be more vulnerable to the risks associated with PIM. Show more
Keywords: Dementia, inappropriate prescribing, pharmacoepidemiology, potentially inappropriate medication, time trend
DOI: 10.3233/JAD-200627
Citation: Journal of Alzheimer's Disease, vol. 79, no. 4, pp. 1459-1470, 2021
Authors: Kristensen, Rachel Underlien | Nørgaard, Ane | Jensen-Dahm, Christina | Gasse, Christiane | Wimberley, Theresa | Waldemar, Gunhild
Article Type: Research Article
Abstract: Background: Polypharmacy, the use of multiple medications, has become increasingly widespread. Information on time trends in polypharmacy in people with dementia is limited, although they may be more susceptible to risks associated with polypharmacy. Objective: To examine changes in the prevalence of polypharmacy and excessive polypharmacy in people with dementia compared to changes in people without dementia. Methods: Repeated cross-sectional study of the entire Danish population aged≥65 from 2000 (n = 790,717) to 2014 (n = 1,028,377) using linked register data on diagnoses, filled prescriptions, and demographic data. Multivariate analyses were performed to explore changes in the prevalence of polypharmacy and excessive …polypharmacy (≥5 and≥10 different prescription drugs). This was done before and after 2011 to examine whether increasing awareness of potential problems associated with polypharmacy has altered the trend. Estimates for people with and without dementia were compared. Results: In people with dementia, the prevalence of polypharmacy increased from 47.3% to 69.4% from 2000 to 2011 and excessive polypharmacy from 7.4% to 20.9%. In people without dementia, polypharmacy increased from 22.7% to 36.1% and excessive polypharmacy from 3.5% to 7.7%. The increase was significantly more marked in people with dementia across all age groups. From 2011 to 2014, the prevalence of polypharmacy and excessive polypharmacy remained relatively stable: Polypharmacy decreased negligibly from 69.4% to 68.1% in people with dementia and from 36.1% to 35.2% in people without dementia. Conclusion: Although the increasing trend has halted, polypharmacy remains widespread in people with dementia. Further research is needed to explore possible implications. Show more
Keywords: Dementia, inappropriate prescribing, pharmacoepidemiology, polypharmacy
DOI: 10.3233/JAD-180427
Citation: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 949-960, 2019
Authors: Stevnsborg, Lea | Jensen-Dahm, Christina | Nielsen, Thomas R. | Gasse, Christiane | Waldemar, Gunhild
Article Type: Research Article
Abstract: Background: Previous studies demonstrated lower quality diagnostic assessment of dementia in immigrant populations, but knowledge about the quality of treatment and care for dementia is still lacking. Objective: To conduct a nationwide registry-based study to determine whether inequality exists regarding access to anti-dementia treatment and care between immigrant and Danish-born patients with dementia. Methods: A cross-sectional register-based study was conducted in the entire elderly (60≥years) population with dementia in Denmark in 2012 (n = 34,877). The use of anti-dementia drugs and residency in a nursing home were compared among Danish-born and Western and non-Western immigrants with dementia. Logistic regression analysis was …done with adjustment for age, sex, comorbidity, marital status, basis of inclusion, and time since dementia diagnosis. Results: Immigrant background was associated with a significantly lower likelihood of receiving anti-dementia drug therapy (odds ratio (OR) [95% confidence interval (CI)]): non-Western = 0.70 [0.56–0.87]; Western = 0.74 [0.63–0.87]). No significant differences were found in type or amount of anti-dementia medication dispensed between the population groups (proxy measure for adherence). Non-Western immigrants were significantly less likely to live in a nursing home (0.52 [0.41–0.65]). Conclusion: This nationwide registry-based study indicated a worrisome difference in access to anti-dementia treatment and care for dementia patients with an immigrant background, but similar levels of adherence compared with the Danish-born population. Further research is necessary to pinpoint barriers to access to suitable healthcare among elderly immigrants with dementia but also to identify and develop culturally sensitive methods for their treatment and care. Show more
Keywords: Dementia, drug therapy, emigrants and immigrants and, healthcare disparities, medication adherence, nursing homes
DOI: 10.3233/JAD-160124
Citation: Journal of Alzheimer's Disease, vol. 54, no. 2, pp. 505-514, 2016
Authors: Kristensen, Rachel Underlien | Nørgaard, Ane | Jensen-Dahm, Christina | Gasse, Christiane | Wimberley, Theresa | Waldemar, Gunhild
Article Type: Research Article
Abstract: Background: Polypharmacy (use of ≥5 different medications) and potentially inappropriate medication (PIM) are well-known risk factors for numerous negative health outcomes. However, the use of polypharmacy and PIM in people with dementia is not well-described. Objective: To examine the prevalence of polypharmacy and PIM in older people with and without dementia in a nationwide population. Methods: Cross-sectional study of the Danish population aged ≥65 in 2014 (n = 1,032,120) based on register data, including information on diagnoses and dispensed prescriptions. Polypharmacy and PIM use among people with (n = 35,476) and without dementia (n = 994,231) were compared, stratified by living situation and …adjusted for age, sex, and comorbidity. The red-yellow-green list from the Danish Institute for Rational Pharmacotherapy and the German PRISCUS list were used to define PIM. Results: People with dementia were more frequently exposed to polypharmacy (dementia: 62.6% versus no-dementia: 35.1%, p < 0.001) and likewise PIM (red-yellow-green: 45.0% versus 29.7%, p < 0.001; PRISCUS: 24.4% versus 13.2%, p < 0.001). After adjustments for age, sex, and comorbidity, the likelihood of polypharmacy and PIM was higher for community-dwelling people with dementia than without dementia (odds ratio (OR); [95% confidence interval (CI)] polypharmacy: 1.50 [1.45–1.55]; red-yellow-green: 1.27 [1.23–1.31]; PRISCUS: 1.25 [1.20–1.30]). In contrast, dementia slightly decreased the odds of polypharmacy and PIM in nursing home residents. Conclusion: Use of polypharmacy and PIM were widespread in the older population and more so in people with dementia. This could have negative implications for patient-safety and demonstrates the need for interventions to improve drug therapy in people with dementia. Show more
Keywords: Dementia, inappropriate prescribing, pharmacoepidemiology, polypharmacy, potentially inappropriate medication list
DOI: 10.3233/JAD-170905
Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 383-394, 2018
Authors: Nørgaard, Ane | Jensen-Dahm, Christina | Gasse, Christiane | Hansen, Elsebet Steno | Waldemar, Gunhild
Article Type: Research Article
Abstract: Background: Antipsychotics and other psychotropics are frequently used to treat neuropsychiatric symptoms in patients with dementia, even though the evidence for effect is limited. Concerns have been raised about the safety of antipsychotics, but concomitant use of multiple psychotropic drug classes (psychotropic polypharmacy) may also pose a risk for patients. Objective: To investigate the prevalence and predictors associated with use of psychotropic polypharmacy in patients with dementia. Methods: A population-based study using nationwide registers. Patients with dementia were identified among all Danish residents ≥65 years on January 1, 2012. Data on prescriptions and comorbidity was included in the analysis. Overlapping …prescriptions for different psychotropic drug classes were used to determine psychotropic polypharmacy. A multivariable logistic regression analysis was conducted to evaluate factors independently associated with the prescription of other psychotropic drug classes among patients already using antipsychotics. Results: Among all patients registered with dementia (34,553), 25.3% (8,728) used ≥2 psychotropic drugs. Among patients treated with antipsychotics 75.8% (5,403) used at least one other psychotropic drug during the antipsychotic treatment period. Nursing home residency, number of non-psychotropic medications used in 2011, and prior psychiatric diagnosis were associated with psychotropic polypharmacy among antipsychotic drug users. The most frequent combination of psychotropic drugs was antipsychotics and antidepressants. Conclusion: Concomitant use of psychotropic drugs was frequent in dementia patients. Patients living in nursing homes had the highest risk of receiving a combination of antipsychotics and other psychotropic drugs. Concomitant use of psychotropics may cause adverse events, and potential consequences for patients’ safety call for further investigation. Show more
Keywords: Antidepressant drugs, antipsychotic drugs, dementia, pharmacoepidemiology, polypharmacy, psychotropic drugs
DOI: 10.3233/JAD-160828
Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 707-716, 2017
Authors: Nørgaard, Ane | Jensen-Dahm, Christina | Gasse, Christiane | Hansen, Hanne Vibe | Waldemar, Gunhild
Article Type: Research Article
Abstract: Background: Antipsychotics are often used to treat neuropsychiatric symptoms in dementia, but the evidence for effect is limited. Antipsychotics have been associated with increased risk of adverse events and mortality in patients with dementia, leading to safety regulations worldwide. Objective: To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. Methods: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000–2012. Data included prescriptions, discharge diagnoses, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients …with dementia within 4-year age bands were performed. Results: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012. The decreasing use of antipsychotics was accompanied by decreasing use of anxiolytics and hypnotics/sedatives, but an increase in the use of antidepressants from 43.3% in 2000 to 53.8% in 2012. These changes were significant across almost all age groups. Treatment intensity among patients using antipsychotics increased as the annual median number of defined daily doses (DDD) increased from 33.3 to 42.0 DDD. Conclusions: The changing patterns of psychotropic drug use may be caused by warnings against use of antipsychotics. Further research is needed to explore the implications for patient safety. Show more
Keywords: Antidepressant drugs, antipsychotic drugs, dementia, neuropsychiatric symptoms, time trend
DOI: 10.3233/JAD-150481
Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 211-220, 2016
Authors: Zakarias, Johanne Købstrup | Jensen-Dahm, Christina | Nørgaard, Ane | Roos, Peter | Gasse, Christiane | Phung, Thien Kieu Thi | Waldemar, Gunhild
Article Type: Research Article
Abstract: Background: Early and accurate diagnosis of dementia opens the door to appropriate treatment, support, and counseling. Despite availability of evidence-based guidelines for diagnostic evaluation of dementia, the diagnostic rate in people with dementia is low and the quality of dementia diagnoses is unknown. Objective: The overall aim of this register-based study was to analyze the quality of diagnostic evaluation of dementia by assessing nationwide geographical variations in a range of indicators. Methods: A register-based cross-sectional study of the entire Danish population aged 65 years or older in 2015 was conducted. The surrogate indicators for diagnostic quality included 1) prevalence rates …of dementia diagnoses, 2) incidence rates of dementia diagnoses, 3) age at first diagnosis of dementia, 4) medical specialty responsible for diagnosis, 5) diagnostic rate of dementia subtypes, and 6) use of anti-dementia medication. The indicators were compared across the five Danish regions. Results: The national prevalence and incidence of registered dementia diagnoses was 3.0% and 0.5%, respectively. The proportion of patients diagnosed at a dementia specialist department ranged from 60.9% to 90.5% across the five regions, subtype specific diagnosis ranged from 45.3% to 75.5%, and use of anti-dementia medication ranged from 29.2% to 58.3%. Conclusion: The observed geographical variations in dementia diagnoses and treatment indicate inequality in the access to appropriate diagnostic evaluation and care for patients with dementia. Our findings call for more awareness of the benefits of timely diagnosis and for improvement in the quality of diagnostic evaluation of dementia. Show more
Keywords: Dementia, diagnosis, geography, health care quality assessment, register
DOI: 10.3233/JAD-190030
Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 513-520, 2019
Authors: Jensen-Dahm, Christina | Waldemar, Gunhild | Staehelin Jensen, Troels | Malmqvist, Lasse | Moeller, Michelle Mai | Andersen, Birgitte Bo | Høgh, Peter | Ballegaard, Martin
Article Type: Research Article
Abstract: Background: Autonomic function has received little attention in Alzheimer’s disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function. Objective: To investigate autonomic function using standardized techniques in patients with AD and healthy age-matched controls. Method: Thirty-three patients with mild to moderate AD and 30 age- and gender-matched healthy controls, without symptoms of autonomic dysfunction, underwent standardized autonomic testing with deep breathing, Valsalva maneuver, head-up tilt, and isometric handgrip test. Brachial pressure curve and electrocardiogram were recorded for off-line analysis …of blood pressure and beat-to-beat heart rate (HR). Results: AD patients had impaired blood pressure responses to Vasalva maneuver (p < 0.0001) and HR response to isometric contraction (p = 0.0001). A modified composite autonomic scoring scale showed greater degree of autonomic impairment in patients compared to controls (patient: 2.1 ± 1.6; controls: 0.9 ± 1.1, p = 0.001). HR response to deep breathing and Valsalva ratio were similar in the two groups. Conclusion: We identified autonomic impairment ranging from mild to severe in patients with mild to moderate AD, who did not report autonomic symptoms. Autonomic impairment was mainly related to impairment of sympathetic function and evident by impaired blood pressure response to the Vasalva maneuver. The clinical implications of this finding are that AD may be associated with autonomic disturbances, but patients with AD may rarely report symptoms of autonomic dysfunction. Future research should systematically evaluate symptoms of autonomic function and characterize risk factors associated with autonomic dysfunction. Show more
Keywords: Alzheimer’s disease, autonomic function, orthostatic hypotension, tilt test, Valsalva maneuver
DOI: 10.3233/JAD-150169
Citation: Journal of Alzheimer's Disease, vol. 47, no. 3, pp. 681-689, 2015
