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• W2461963945 abstract "To the Editor: Alzheimer's disease (AD) is common in older people. Its pharmacotherapy is based on cholinesterase inhibitors (AChEIs; donepezil, galantamine, rivastigmine) and memantine.1 AChEIs increase the concentration of acetylcholine in cholinergic synapses and slow down progression of the disease. Older people often also use urinary anticholinergics (UAcs) to manage urinary incontinence.2 Urinary incontinence is more prevalent in persons with dementia than in those without.3 Functional incontinence is especially common in individuals with AD because of their cognitive disability and lack of motivation. Individuals with AD have prominent urinary disturbances, but they are uncommon in the early stages of the disease.4 Even though the mechanisms of action of these two drug groups are opposite, and they should therefore not be used together, the concomitant use of AChEIs and UAcs is common (9–10%).3, 5 One of the adverse effects of AChEIs is urinary incontinence, which may account for the use of UAcs, but to the knowledge of the authors, there is no study confirming this link. Therefore, whether the use of UAcs increases after initiation of a cholinesterase inhibitor was investigated. To avoid urinary disturbances caused by AD, periods of 6 and 12 months after initiation of AD medication were focused on. Data from the Medication Use and Alzheimer's Disease Study were used.6 Of 70,718 persons with newly diagnosed AD from 2005 to 2011 in Finland, 65,189 purchased antidementia drugs, 64,567 started use with an AChEI or memantine (concomitant users excluded), and 62,578 were not using UAcs at baseline. Data on drug use and comorbidities were collected from nationwide prescription, special reimbursement, and hospital discharge registers. Follow-up started at initiation of AChEI or memantine use and ended after 6 or 12 months, upon death, more than 90 days of hospitalization or institutionalization, change of antidementia drug group, end of antidementia drug use, or outcome (initiation of UAc use). Cox proportional hazards models were used to measure time to outcome, comparing AChEI users with memantine users. Each covariate and time to UAc initiation was used in unadjusted analyses. An adjusted multivariate Cox model included covariates associated with drug choice and UAc initiation. During the first 6 months after initiation of AD medication, UAc was initiated in 729 persons (1.2% of those using AChEI, 0.8% of those using memantine, P < .001) (Table 1). UAcs were more likely to be initiated in persons taking AChEIs than in those taking memantine (hazard ratio (HR) = 1.42, 95% confidence interval (CI) = 1.22–1.64, adjusted HR (aHR) = 1.47, 95% CI = 1.17–1.86). General practitioners prescribed 41.5% of the initiations of UAc for individuals taking an AChEI, specialists in general practice prescribed 20.0%, surgeons prescribed 14.7%, gynecologists prescribed 9.8%, and geriatricians prescribed 5.9%. During the first year, UAcs were initiated in 1,103 persons (1.8% of AChEI, 1.2% of memantine, P < .001; HR = 1.43, 95% CI = 1.24–1.66, aHR = 1.41, 95% CI = 1.17–1.69). The patterns of prescribing physicians were similar at this time point. There was no difference between donepezil, rivastigmine, and galantamine use in risk of UAc initiation (data not shown). The risk of UAc initiation was greater in AChEI than memantine users. Because of short follow-up, the percentages of persons starting UAc were small, but statistically significant differences were found between AChEI and memantine users. In addition to AChEI use, diabetes mellitus was associated with UAc initiation, which may be related to diabetic neuropathy.7 The reason for the greater risk of UAc initiation associated with antidepressants is unknown, although they may affect detrusor overactivity.8 Alternatively, antipsychotics decreased the risk of UAc initiation, which the anticholinergic properties that they often possess may explain.9 Urinary incontinence is a well-known adverse effect of cholinesterase inhibitors, and these results suggest that UAcs are started to manage these effects rather than urinary problems caused by advanced AD. This combination of drugs may decrease the efficacy of the dementia pharmacotherapy, leading to an unnecessary decrease in cognition and functioning. Primary care providers initiated more than half of the UAcs, and surgeons and gynecologists initiated one-fourth, suggesting that primary care providers, but also physicians with other specialties treating older persons, should be informed that the concurrent use of these two drug groups should be avoided. Urinary incontinence is a great burden of care for family and caretakers, but other methods of treating it are preferred (e.g., mirabegrone, biofeedback, physiotherapy). Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Pasi Lampela received a grant from the Päivikki and Sakari Sohlberg Foundation that did not affect this work in any way. Author Contributions: Lampela, Taipale, Hartikainen: analysis and interpretation of data, preparation of manuscript. Sponsor's Role: None." @default.
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• W2461963945 date "2016-07-01" @default.
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• W2461963945 title "Use of Cholinesterase Inhibitors Increases Initiation of Urinary Anticholinergics in Persons with Alzheimer's Disease" @default.
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• W2461963945 doi "https://doi.org/10.1111/jgs.14220" @default.
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