Anticholinergic burden and risk of stroke and death in people with different types of dementia

Background. Anticholinergic burden is associated with poorer cognitive and functional outcomes in people with dementia. However, the impact of anticholinergics on significant adverse outcomes such as stroke has not been studied previously. Objective. To investigate the association between total anticholinergic cognitive burden (ACB) and risk of stroke and death in people with different dementia subtypes. Methods. This was a cohort study of 39107 people with dementia and no prior history of stroke registered in the Swedish Dementia Registry (SveDem) from 2008 – 2014. Data were extracted from the Swedish Prescribed Drug Register, the Swedish National Patient Register and the Swedish Total Population Register. Competing risk regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-varying ACB score and risk of stroke and all-cause mortality. Results. During a mean follow-up period of 2.31 (standard deviation 1.66) years, 11224 (28.7%) individuals had a stroke or died. Compared with non-users of anticholinergic medications, ACB score of 1 (HR 1.09, 95%CI 1.04 – 1.14) and ACB score of ≥2 (HR 1.20, 95%CI 1.14 – 1.26) increased the risk of developing the composite outcome of stroke and death. When stratifying by dementia disorder, the association remained significant in Alzheimer’s disease, mixed dementia and vascular dementia. Conclusions. The use of anticholinergic medicines may be associated with an increased risk of stroke and death in people with dementia. A dose-response relationship was observed. Careful consideration should be made when prescribing medications with anticholinergic properties to people with dementia.FORTEAccepte

Drug Treatment in Older People before and after the Transition to a Multi-Dose Drug Dispensing System - A Longitudinal Analysis

Tverrsnittstudie, undersøker assosiasjonen mellom multidose og polyfarmasi hos eldre.Background: an association has been found between multi-dose drug dispensing (MDD) and use of many drugs. The aim of this study was to investigate the nature of this association, by performing a longitudinal analysis of the drug treatment before and after the transition to MDD. Methods: inclusion critera in this register-based study were inhabitants in Region Västra Götaland, Sweden, who, at ≥65 years of age and between 1st July 2006 and 30th June 2010, filled their first MDD prescription. For each individual, prescribed drugs were estimated at three month intervals before and after (maximum 3 years, respectively) the first date of filling an MDD prescription (index date). Results: a total of 30,922 individuals matched the inclusion criteria (mean age: 83.2 years; 59.9% female). There was a temporal association between the transition to MDD and an increased number of drugs: 5.463.9 and 7.563.8 unique drugs three months before and after the index date, respectively, as well as worse outcomes on several indicators of prescribing quality. When either data before or after the index date were used, a multi-level regression analysis predicted the number of drugs at the index date at 5.76 (95% confidence limits: 5.71; 5.80) and 7.15 (7.10; 7.19), respectively, for an average female individual (83.2 years, 10.8 unique diagnoses, 2.4 healthcare contacts/three months). The predicted change in the number of drugs, from three months before the index date to the index date, was greater when data before this date was used as compared with data after this date: 0.12 (0.09; 0.14) versus 0.02 (20.01; 0.05). Conclusions: after the patients entered the MDD system, they had an increased number of drugs, more often potentially harmful drug treatment, and fewer changes in drug treatment. These findings support a causal relationship between such a system and safety concerns as regards prescribing practices

Choosing Wisely? Measuring the Burden of Medications in Older Adults near the End of Life: Nationwide, Longitudinal Cohort Study

Abstract Background The burden of medications near the end of life has recently come under scrutiny, because several studies suggested that people with life-limiting illness receive potentially futile treatments. Methods We identified 511,843 older adults (>65 years) who died in Sweden between 2007 and 2013 and reconstructed their drug prescription history for each of the last 12 months of life through the Swedish Prescribed Drug Register. Decedents' characteristics at time of death were assessed through record linkage with the National Patient Register, the Social Services Register, and the Swedish Education Register. Results Over the course of the final year before death, the proportion of individuals exposed to ≥10 different drugs rose from 30.3% to 47.2% ( P Conclusion Polypharmacy increases throughout the last year of life of older adults, fueled not only by symptomatic medications but also by long-term preventive treatments of questionable benefit. Clinical guidelines are needed to support physicians in their decision to continue or discontinue medications near the end of life

Antidepressant Use and Suicide Rates in Adults Aged 75 and Above: A Swedish Nationwide Cohort Study

Background: The treatment of depression is a main strategy for suicide prevention in older adults. We aimed to calculate suicide rates by antidepressant prescription patterns in persons aged ≥ 75 years. A further aim was to estimate the contribution of antidepressants to the change in suicide rates over time. Methods: Swedish residents aged ≥ 75 years (N = 1,401,349) were followed between 2007 and 2014 in a national register-based retrospective cohort study. Biannual suicide rates were calculated for those with selective serotonin reuptake inhibitor (SSRI) single use, mirtazapine single use, single use of other antidepressants and use of ≥ 2 antidepressants. The contribution of antidepressants to the change in biannual suicide rates was analyzed by decomposition analysis. Results: There were 1,277 suicides. About one third of these were on an antidepressant during their last 3 months of life. In the total cohort, the average biannual suicide rate in non-users of antidepressants was 13 per 100,000 person-years. The corresponding figure in users of antidepressants was 34 per 100,000 person-years. These rates were 25, 42 and 65 per 100,000 person-years in users of SSRI, mirtazapine and ≥ 2 antidepressants, respectively. In the total cohort, antidepressant users contributed by 26% to the estimated increase of 7 per 100,000 in biannual suicide rates. In men, biannual suicide rates increased by 11 suicides per 100,000 over the study period; antidepressant users contributed by 25% of the change. In women, those on antidepressant therapy accounted for 29% of the estimated increase of 4.4 per 100,000. Conclusion: Only one third of the oldest Swedish population who died by suicide filled an antidepressant prescription in their last 3 months of life. Higher suicide rates were observed in mirtazapine users compared to those on SSRIs. Users of antidepressants accounted for only one quarter of the increase in the suicide rate. The identification and treatment of suicidal older adults remains an area for prevention efforts.This study was funded by the Swedish Research Council (VR) 2016-01590, the Swedish Research Council for Health, Working Life and Welfare (Forte) 2016-07097, and ALFGBG433511 (Grants to MW). The sponsors had no role in the study design; collection, analysis, and interpretation of the data; writing of the report; or decision to submit the paper for publication. Söderström-König Foundation (to KH, Grant number 844351

Association between Multi-Dose Drug Dispensing and Quality of Drug Treatment – A Register-Based Study

BACKGROUND: In the elderly in Scandinavia, multi-dose drug dispensing (MDD) is a common alternative to ordinary prescriptions (OP). MDD patients receive their drugs in unit bags, one for each dose occasion. The prescribing procedure differs between MDD and OP. The aim of the present study was to investigate the association between MDD and quality of drug treatment (QDT). METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was performed of all inhabitants in Region Västra Götaland alive on December 31st 2007, aged ≥65 years, with ≥1 prescribed drug and ≥2 health care visits for ≥2 diagnoses for obstructive pulmonary disease, diabetes mellitus, and/or cardiovascular disease in 2005-2007 (n = 24,146). For each patient, drug treatment on December 31st 2007 was estimated from drugs registered in the Swedish Prescribed Drug Register. QDT was evaluated according to established quality indicators (≥10 drugs, Long-acting benzodiazepines, Drugs with anticholinergic action, ≥3 psychotropics, and Drugs combinations that should be avoided). Logistic regression, with adjustments for age, sex, burden of disease, and residence, was performed to investigate the association between MDD and QDT. Mean age was 77 years, 51% were females, and 20% used MDD. For all quality indicators, the proportion of patients with poor QDT was greater in patients with MDD than in patients with OP (all P<0.0001). Unadjusted and adjusted odds ratios (95% confidence intervals) for poor QDT (MDD patients vs. OP patients) ranged from 1.47 (1.30-1.65) to 7.08 (6.30-7.96) and from 1.36 (1.18-1.57) to 5.48 (4.76-6.30), respectively. CONCLUSIONS/SIGNIFICANCE: Patients with MDD have poorer QDT than patients with OP. This cannot be explained by differences in age, sex, burden of disease, or residence. These findings must be taken into account when designing alternative prescribing systems. Further research is needed to evaluate causative factors and if the findings also apply to other dose dispensing systems

Comparing estimated cost per patient for dementia care: Two municipalities and Swedish national population data

Abstract Aim: To evaluate a collaborative dementia program for its influence on cost and in which dementia care specialists and primary care centres collaborate with the municipality and, thereby, effect direct cost of dementia care. Methods: The cost of illness (COI) study investigated the cost of dementia care to the municipality, specifically on the Municipality of Kalmar. Municipal costs in the Municipality of Älvsjö and national cost figures for Sweden were used as comparisons. The major costs related to dementia care, such as the cost of home care, day-care centers, and nursing home placement were extracted from municipality records. Results: The yearly municipal cost per person with dementia in Kalmar ranged from 14,206 C to 26,334 C (17,684 USD to 32,780 USD) as compared to Älvsjö 10,610 C to 30,464 C (13,207 USD to 37,921 USD), and Swedish national figures showing costs from 23,600 C to 36,459 C (29,378 USD to 45,384 USD), per patient, annual cost. In Kalmar, 60% of the patients with dementia received help from the municipality as compared to 69% in Älvsjö. Conclusions: Implementation of such a dementia program is a recommendation that would not increase the cost for dementia care in the Municipality of Kalmar

Caffeine Modulates Food Intake Depending on the Context That Gives Access to Food: Comparison With Dopamine Depletion

Caffeine is a methylxanthine consumed in different contexts to potentiate alertness and reduce fatigue. However, caffeine can induce anxiety at high doses. Caffeine is also a minor psychostimulant that seems to act as an appetite suppressant, but there are also reports indicating that it could stimulate appetite. Dopamine also is involved in food motivation and in behavioral activation. In the present series of experiments, we evaluated the effects of acute administration of caffeine on food consumption under different access conditions. CD1 male adult mice had access to highly palatable food (50% sucrose) in a restricted but habitual context, under continuous or intermittent access as well as under anxiogenic, or effortful conditions. Caffeine (2.5-20.0 mg/kg) increased intake at the highest dose under familiar continuous and intermittent access. However, this high dose reduced food intake in the dark-light paradigm. In contrast, a dopamine-depleting agent, tetrabenazine (TBZ; 1.0-8.0 mg/kg) did not affect food intake in any of those experimental conditions. In the T-maze-barrier task that evaluates seeking and taking of food under effortful conditions, caffeine (10.0 mg/kg) decreased latency to reach the food, but did not affect selection of the high-food density arm that required more effort, or the total amount of food consumed. In contrast, TBZ (4.0 mg/kg) reduced selection of the high food density arm with the barrier, thus affecting amount of food consumed. Interestingly, a small dose of caffeine (5.0 mg/kg) was able to reverse the anergia-inducing effects produced by TBZ in the T-maze. These results suggest that caffeine can potentiate or suppress food consumption depending on the context. Moreover, caffeine did not change appetite, and did not impair orientation toward food under effortful conditions, but it rather helped to achieve the goal by improving speed and by reversing performance to normal levels when fatigue was induced by dopamine depletion

Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study

<p>Abstract</p> <p>Background</p> <p>Previous studies have found associations between the use of central nervous system medication and the risk of cognitive decline in the aged. Our aim was to assess whether the use of a single central nervous system (CNS) medication and, on the other hand, the combined use of multiple CNS medications over time are related to the risk of cognitive decline in an older (≥ 65 yrs) population that is cognitively intact at baseline.</p> <p>Methods</p> <p>We conducted a longitudinal population-based study of cognitively intact older adults. The participants were 65 years old or older and had Mini-Mental State Examination (MMSE) sum scores of 24 points or higher. The study included a 7.6-year follow-up. The use of benzodiazepines and related drugs (BZDs), antipsychotics (APs), antidepressants (ADs), opioids (Ops), anticholinergics (AChs) and antiepileptics (AEs) was determined at baseline and after a 7.6-years of the follow-up period. Cognitive functioning was used as an outcome variable measured with MMSE at baseline and at the mean follow-up of 7.6 years. Control variables were adjusted with analyses of covariance.</p> <p>Results</p> <p>After adjusting for control variables, the use of Ops and the concomitant use of Ops and BZDs as well as the use of Ops and any CNS medication were associated with cognitive decline. The use of AChs was associated with decline in cognitive functioning only in men.</p> <p>Conclusions</p> <p>Of all the CNS medications analyzed in this study, the use of Ops may have the greatest effect on cognitive functioning in the ageing population. Due to small sample sizes these findings cannot be generalized to the unselected ageing population. More studies are needed concerning the long-term use of CNS medications, especially their concomitant use, and their potential cognitive effects.</p