Use Of Acetylcholinesterase Inhibitors Research Articles

Do Acetylcholinesterase Inhibitors Prevent or Delay Psychotropic Prescribing in People With Dementia? Analyses of the Swedish Dementia Registry

ObjectivesTo investigate whether acetylcholinesterase inhibitor (AChEI) use prevents or delays subsequent initiation of psychotropic medications in people with Alzheimer's disease (AD) and Lewy body dementia (LBD). MethodsCohort study of 17,763 people with AD and LBD, without prior psychotropic use at time of dementia diagnosis, registered in the Swedish Dementia Registry from 2007 to 2015. Propensity score-matched regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent AChEI use and risk of psychotropic initiation. ResultsCompared with matched comparators, AChEI users had a lower risk of antipsychotic (HR: 0.85, 95%CI: 0.75–0.95) and anxiolytic (HR: 0.76, 95%CI: 0.72–0.80) initiation. In subanalyses, this association remained significant at higher AChEI doses, and in AD but not LBD. There were no associations between AChEI use and initiation of antidepressants or hypnotics. ConclusionAChEI use may be associated with lower risk of antipsychotic and anxiolytic initiation in AD, particularly at higher doses. Further investigation into aceytylcholinesterase inhibitors in behavioral and psychological symptoms of dementia management in LBD is warranted.

Acetylcholinesterase inhibitors in Alzheimer's disease influence Zinc and Copper homeostasis

BackgroundAlzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored. ObjectivesThe aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use. Methods and Results84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI naïve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI naïve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1β concentration and lower Zip2 lymphocytic expression vs. naïve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time. ConclusionOur data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.

Nicotine-like discriminative stimulus effects of acetylcholinesterase inhibitors and a muscarinic receptor agonist in Rhesus monkeys

Acetylcholinesterase (AChE) inhibitors and positive allosteric nicotinic acetylcholine receptor (nAChR) modulators are potential pharmacotherapies for nicotine dependence. Because some smoking cessation aids (e.g. varenicline) appear to work by mimicking the effects of nicotine, we used drug discrimination to examine whether AChE inhibitors and nAChR allosteric modulators mimic the effects of nicotine. Rhesus monkeys discriminated 1.78 mg/kg of nicotine s.c. under an FR5 schedule of stimulus-shock termination. Nicotine and the AChE inhibitors donepezil and galantamine dose-dependently increased responding on the nicotine-appropriate lever with ED50 values of 0.35, 0.22, and 0.77 mg/kg, respectively. Donepezil (0.56 mg/kg) produced nicotine-like effects for at least 6 h, whereas the duration of action of galantamine (1.78 mg/kg) was less than 3 h. The positive allosteric nAChR modulator PNU-120596 (up to 10 mg/kg) and midazolam (up to 1.0 mg/kg) produced no more than 22% nicotine-lever responding. Oxotremorine, a muscarinic acetylcholine receptor agonist that was used to explore the extent to which muscarinic receptor agonism might contribute to the effects of AChE inhibitors, produced 94% nicotine-lever responding (ED50 value 0.013 mg/kg). The muscarinic antagonist atropine significantly antagonized the effects of both oxotremorine and nicotine; however, the dose of atropine antagonizing oxotremorine was smaller than the dose required to antagonize nicotine. Collectively, these results suggest that AChE inhibitors can mimic the effects of nicotine by indirectly stimulating both nicotinic and muscarinic receptors. Inasmuch as some smoking cessation aids work by exerting nicotine-like effects, the current results are consistent with the potential use of AChE inhibitors as novel smoking cessation aids.

Memantine and Acetylcholinesterase Inhibitor Use in Alzheimer's Disease Clinical Trials: Potential for Confounding by Indication.

Acetylcholinesterase inhibitors (AChEIs) and memantine are commonly prescribed medications for Alzheimer's disease (AD). Their concurrent use in AD randomized clinical trials (RCTs) is generally allowed but their effect in outcome measures is unsettled. To evaluate whether use of AChEIs and/or memantine across AD RCTs are associated with different rates of cognitive/functional decline. We pooled data from 5 RCTs of mild to moderate AD conducted by the Alzheimer's Disease Cooperative Study (ADCS) between 2002-2013. 1,423 participants with MMSE of 14-26 and completion of 12-18 months follow-up visits were analyzed. Trials did not randomize with respect to AChEIs or memantine. We defined 4 groups: AChEI (27%), memantine (16%), AChEIs+memantine (46%), and non-users (11%). Outcome measures were change in ADAS-cog-11, ADCS-ADL, and MMSE from baseline to 18 months. Fisher's exact test, Wilcoxon signed rank, and Spearman's tests were used to identify confounding variables. Mixed model repeated measures were used for adjustments and pairwise tests for comparing change in scores. Age, apolipoprotein E, and initial MMSE were identified as covariates. Memantine and/or AChEIs users had greater impairment at entry than non-users. There was a significant decline on the ADAS-cog-11 in the memantine (estimate -4.2 p < 0.0001) and AChEIs+memantine groups (estimate -3.5 p < 0.0001) than non-users, while there was significantly more decline in MMSE (estimate 2.5 p < 0.0001) and ADCS-ADL in the AChEIs+memantine group (estimate 4.3 p < 0.0001)Conclusion: Memantine monotherapy or combined with AChEIs are associated with more rapid cognitive and functional decline than non-users. We postulated a potential selection bias by indication.

Patterns of Dementia Treatment and Frank Prescribing Errors in Older Adults With Parkinson Disease

Dementia is common in Parkinson disease, but few data exist on dementia treatment patterns or the concurrent use of acetylcholinesterase inhibitors (ACHEIs) and anticholinergic medications, a frank prescribing error. To describe dementia treatment patterns, and to determine the extent to which the concurrent use of ACHEIs and drugs with strong anticholinergic activity occurs among individuals with Parkinson disease in the United States. This cross-sectional analysis included adult Medicare beneficiaries (aged 65 years or older) with Parkinson disease diagnosis with 12 consecutive months of inpatient, outpatient, and prescription drug coverage from January 1, 2014, through December 31, 2014. Beneficiaries with other parkinsonian syndromes were excluded. Demographic, geographic, prescription claims, and other data were extracted from the 2014 Carrier, Beneficiary Summary, and Prescription Drug Event research identifiable files of the Centers for Medicare & Medicaid Services. Data analysis was conducted from August 1, 2017, to November 30, 2017. Primary outcomes were use of dementia drug, specific dementia medication, and concurrent exposure to a high-potency anticholinergic drug and an ACHEI. Descriptive analyses and multivariable logistic regression models determined the extent to which patient characteristics and comorbid conditions were associated with dementia treatment or with a high-potency anticholinergic and ACHEI never event. Of 268 407 Medicare beneficiaries with Parkinson disease (mean [SD] age, 78.9 [7.5]; 134 575 male [50.1%]), most were identified in the files as white (232 831 [86.7%]), followed by black (14 629 [5.5%]), Hispanic (7176 [2.7%]), Asian (7115 [2.7%]), and Native American (874 [0.3%]). Among these beneficiaries, 73 093 (27.2%) were given a prescription for at least 1 antidementia medication. The most commonly prescribed medication was donepezil hydrochloride (46 027 [63.0%] users), followed by memantine hydrochloride (30 578 [41.8%] users) and rivastigmine tartrate (19 278 [26.4%] users). Dementia drugs were more likely to be prescribed to black (adjusted odds ratio [AOR], 1.33; 95% CI, 1.28-1.38) and Hispanic (AOR, 1.28; 95% CI, 1.22-1.35) beneficiaries and less likely for Native American beneficiaries (AOR, 0.62; 95% CI, 0.51-0.74). Women were less likely than men to be given a prescription for dementia medication (AOR, 0.85; 95% CI, 0.84-0.87). Of the 64 017 beneficiaries receiving an ACHEI, 28 495 (44.5%) experienced at least 1 high-potency anticholinergic-ACHEI event. Hispanic (AOR, 1.11; 95% CI, 1.00-1.23) and women (AOR, 1.30; 95% CI, 1.25-1.35) beneficiaries had greater odds of experiencing this never event. Statistically significant clusters of the prevalence of this prescribing error were observed across the United States (Moran I = 0.24; P < .001), with clusters of high prevalence in the southern and midwestern states. Dementia medication use by persons with Parkinson disease varies by race/ethnicity and sex; potentially inappropriate prescribing is common among those being treated for cognitive impairment and varies by race/ethnicity, sex, and geography. These findings may serve as national and local targets for improving care quality and outcomes for persons with Parkinson disease.

ACETYLCHOLINESTERASE INHIBITOR THERAPY IN MILD COGNITIVE IMPAIRMENT: YES OR NO?

Acetylcholinesterase inhibitors (AChEI) are frequently prescribed for the symptomatic treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. AChEIs use, genetic, biological and neurological outcomes data were collected during the three phases of the Alzheimer Disease Neuroimaging Initiative (ADNI1, ADNIGO, ADNI2). Linear regression models were used to compare the treatment effect - on changes in MMSE and CDR-SB scores during a time course of 2 years. MCI subjects treated with AChEIs showed a greater decline in MMSE and a greater rise in CDR-SB after 2-year compared to non-treated ones. Examining the data further, we found a significant association between treatment duration and AChEIs on MMSE decline in the treated group. A similar association between duration of therapy and increased CDR-SB was observed. Our findings thus indicate a faster decline in MMSE and faster rise CDR-SB scores in subjects treated with AChEIs compared to the untreated group. We then stratified by APOE4 genotypes and found a trend for steeper cognitive changes in treated APOE4 carriers compared to treated non-carriers. In a sub-group of MCI treated subjects, we also found that cerebrospinal fluid AD biomarkers (i.e. amyloid-beta and p-tau) were significantly different at baseline compared to the non-treated MCIs. This indicates that the worsening in cognitive decline observed in the treatment group may not be only associated with the use of AChEIs but also due to the natural history of the disease progression. Our findings have an important implication for MCI management. Thus, it opens up the discussion of the off-label use of AChEIs in MCI and the evaluation of the risks versus the benefits of such treatment approach if there is no alternative to AChEIs.

Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia

IntroductionThe aim of this study was to investigate the association between acetylcholinesterase inhibitor (AChEI) use and risk of ischemic stroke and death in people with dementia. MethodsA cohort study of 44,288 people with dementia registered in the Swedish Dementia Registry from 2007 to 2014. Propensity score-matched competing risk regression models were used to compute hazard ratios and 95% confidence intervals for the association between time-dependent AChEI use and risk of stroke and death. ResultsCompared with matched controls, AChEI users had a lower risk of stroke (hazard ratio: 0.85, 95% confidence interval: 0.75–0.95) and all-cause death (hazard ratio: 0.76, 95% confidence interval: 0.72–0.80). After considering competing risk of death, high doses (≥1.33 defined daily doses) of AChEI remained significantly associated with reduced stroke risk. DiscussionThe use of AChEIs in people with dementia may be associated with reduced risk of ischemic stroke and death. These results call for a closer examination of the cardiovascular effects of AChEIs.

Trends in the Prescription and Long-Term Utilization of Antidementia Drugs Among Patients with Alzheimer's Disease in Spain: A Cohort Study Using the Registry of Dementias of Girona.

Acetylcholinesterase inhibitors (AChEIs) and the N-methyl D-aspartate-antagonist memantine are indicated for the symptomatic treatment of Alzheimer's disease (AD). Our aims were to describe the baseline characteristics of patients with AD according to prescription of these treatments after the diagnostic work-up to describe long-term trends in the use of these medications and to identify baseline characteristics associated with the frequency of use of each treatment. This was a cohort study with a sample of 2992 patients with AD recorded in the Registry of Dementias of Girona (ReDeGi) between 2007 and 2014. Consumption of AChEIs and memantine was assessed using the Pharmacy Unit database from the Public Catalan Healthcare Service. We used generalized estimating equation analyses to identify the baseline characteristics associated with the consumption of AChEIs and memantine over time. Most of the patients (70.4%; 95% confidence interval [CI] 68.7-72.0) were prescribed antidementia medication at the time of diagnosis. Of these, 75.0% (95% CI 73.1-76.8) were prescribed AChEIs, 14.7% (95% CI 13.2-16.3) were prescribed an AChEI plus memantine, and 10.3% (95% CI 9.0-11.6) were prescribed memantine. Advanced age reduced the likelihood of AChEI consumption. Mild dementia severity increased the use of AChEIs, and moderate-advanced dementia increased the likelihood of memantine consumption. After diagnosis, the likelihood of AChEI consumption decreased from the first year until the fifth, whereas the likelihood of memantine consumption, either alone or in combination with AChEIs, increased. Antidementia drug use in this study showed the initial use of AChEIs alone with later use of AChEIs in combination with memantine and memantine alone in older patients with severe AD. Our findings are in agreement with current clinical practice guidelines for the pharmacological treatment of AD.

Comedication and Treatment Length in Users of Acetylcholinesterase Inhibitors

Background/Aims: Reduced clinical effect on cognitive decline in dementia by acetylcholinesterase inhibitors (AChEIs) may be due to concurrent use of drugs with anticholinergic properties. The aim was to analyze the incidence of AChEI use and comedication with drugs with anticholinergic properties and other potential unfavorable effects. Methods: A prospective study applying drug use data from the Norwegian Prescription Database. Anticholinergic Drug Scale (ADS) scores were used as a measure of overall anticholinergic burden. Results: Patients with high ADS scores were more frequently discontinuing treatment early. Coprescribing of antipsychotics was strongly associated with early discontinuation of AChEI treatment. Conclusion: Coprescribing with potentially unfavorable medications was common. A high ADS score was associated with early discontinuation of treatment.

Effects of acetylcholinesterase inhibitors on cognitive function in patients with chronic traumatic brain injury: A systematic review.

To undertake a systematic review of the evidence for the effect of acetylcholinesterase inhibitors (AChEIs) on cognition late after moderate or severe traumatic brain injury. Cognitive impairment after traumatic brain injury has significant consequences for the individual and society. Cholinergic pathways play an important role in cognitive processing and a hypocholinergic state exists in the chronic phases after traumatic brain injury. AChEIs are already used off-label to treat patients with traumatic brain injury. PubMed, CINAHL, PsycINFO, the Cochrane Collaboration and Web of Science were searched with pre-specified criteria between 1999 and June 2015. A total of 153 studies were identified. None met pre-specified criteria. The criteria were revised in order to identify studies that may provide useful information despite some risk of bias. Three studies met the revised criteria and were evaluated by 2 reviewers using the Swedish Council on Health Technology Assessment grading system, based on GRADE. Key findings and limitations were tabulated. One study found no effect and 2 found limited effect. Large randomized controlled studies are needed to establish whether AChEIs are effective for cognition late after moderate or severe traumatic brain injury. Clinicians should be aware of the weak evidence base when considering the off-label use of AChEIs.

Impact of acetylcholinesterase inhibitors on the occurrence of acute coronary syndrome in patients with dementia.

The study aimed to investigate the association of acetylcholinesterase inhibitors (AChEIs) use with the risk of acute coronary syndrome (ACS). We conducted a population-based retrospective cohort study of dementia patients during 1 January 1999 to 31 December 2008 using the National Health Insurance Database in Taiwan. New AChEI users during the study period were matched with AChEI nonusers in age-matched and gender-matched cohorts. The risk of ACS associated with use of AChEIs was analyzed using modified Kaplan-Meier analysis and Cox proportional hazard models after adjustment for competing death risk. Use of AChEIs was associated with a lower incidence of ACS (212.8/10,000 person-years) compared to the matched reference cohort (268.7/10,000 person-years). The adjusted hazard ratio for ACS in patients with dementia treated with AChEIs was 0.836 (95% confidence interval, 0.750–0.933; P < 0.001). Further sensitivity analysis of different study populations demonstrated consistent results. A statistical dose–response relationship for AChEI use and ACS risk was significant for the patients with dementia. In patients with dementia, AChEI treatment was associated with decreased risk of ACS.

Challenges in the Pharmacological Management of Nursing Home Residents with Overactive Bladder or Urinary Incontinence.

To determine the proportion of nursing home (NH) residents (NHR) with overactive bladder (OAB) or urinary incontinence (UI) with potential pharmacodynamic contraindications to antimuscarinic treatment because of concomitant anticholinergic medications or acetylcholinesterase inhibitors (AChEIs) and nonpharmacological limitations to antimuscarinic treatment. Cross-sectional retrospective analysis. U.S. skilled nursing facilities. Nursing home residents with a diagnosis of OAB or UI. Linked and deidentified pharmacy claims and Minimum Data Set (MDS) 3.0 records (October 1, 2010 to September 30, 2012). Of NHRs, 71.3% received at least one anticholinergic medication. Medications that can cause or worsen UI were used commonly. AChEIs and antimuscarinic treatment were prescribed concurrently in 24% of NHRs with OAB or UI. NHRs with OAB or UI were more likely to have concurrent moderate to severe cognitive impairment (MSCI) (70.1%) than those without (29.9%) (P < .001). NHRs with or without OAB or UI and with MSCI were more likely to be treated with an anticholinergic medication than those without MSCI (P = .001). When NHRs with MSCI, severe mobility impairment (SMI), and anticholinergic medication and AChEI use were excluded, only a small proportion of NHRs were potential candidates for antimuscarinic treatment (6.6% with OAB or UI, 6.2% with UI). This study advances understanding of the challenges in prescribing antimuscarinic treatment safely and appropriately in elderly NHRs with a high prevalence of drug interactions, underlying MSCI, and SMI.

Use of anti-dementia drugs in home care and residential care and associations with neuropsychiatric symptoms: a cross-sectional study.

BackgroundThe number of people with dementia is increasing alongside the aging population, and most of these patients manifest with neuropsychiatric symptoms (NPS). The objective of this study was to investigate anti-dementia drug use and its associations with NPS.MethodsQuestionnaires on demographic information, current drug use, activities of daily living and NPS were sent to all municipal home care producers and to all institutions providing long-term residential care in the South Savo Hospital District, Finland.ResultsThe study population comprised 2821 persons. Their mean age was 81 years and 68 % were female. Dementia had been diagnosed in 31 % (n = 410) in home care and in 56 % (n = 774) in residential care. Anti-dementia drugs were used by 69 % of patients with dementia. Hyperactivity symptoms were common in residential care patients (n = 456, 33 %), while problems with mood and apathy dominated in home care patients (n = 486, 54 %). In multivariate regression analysis, the mood symptoms and apathy subgroup was associated with use of an acetylcholinesterase inhibitor (AChEI) (OR 1.44; 95 % Cl 1.03–2.02), memantine (OR 1.77, 95 % Cl 1.15–2.72) or their combinations (OR 1.56, 95 % Cl 1.03-2.34). Hyperactivity symptoms were associated with combination therapy of this type (OR 2.03, 95 % Cl 1.36–2.34).ConclusionsThe use of anti-dementia drugs was common in both care settings. The use of any anti-dementia drug or combination was associated with the mood and apathy subgroup. The hyperactivity subgroup was associated with combination use of memantine and AChEI.

Acetylcholinesterase inhibitor modifications: a promising strategy to delay the progression of Alzheimer's disease.

Alzheimer's disease (AD), a fatal, progressive, neurodegenerative disorder, is the most common cause of old-age dementia, accounting for 50–75% of dementia patients. Early stages of AD are marked by vocabulary shrinkage, spatial disorientation, depression, apraxia, and deterioration of recent forms of declarative memory. In course of time, the patients require close supervision due to the loss of cognitive and functional abilities, and at the terminal stages of the disease, all forms of memory are severely impaired with the patients needing nursing home care (World Alzheimer Report, 2013).

Use of drugs with anticholinergic properties among nursing home residents with dementia: a national analysis of Medicare beneficiaries from 2007 to 2008.

Older adults with dementia are vulnerable to the central deteriorating effects of drugs with anticholinergic properties (DAPs). These effects include falls and confusion and may exacerbate dementia-related symptoms. Many individuals with dementia also receive acetylcholinesterase inhibitors (AChEIs), indicated for mild to moderate Alzheimer's disease. AChEIs have opposing effects to DAPs and, consequently, concomitant use of DAPs and AChEIs may further impair cognition among patients with dementia. Our objectives were to (1) evaluate the anticholinergic burden among nursing home (NH) residents with dementia; (2) characterize trends in use of DAPs and concomitant use of DAPs and AChEIs among NH residents with dementia; and (3) identify factors associated with the use of DAPs and concomitant use of DAPs and AChEIs. We conducted a retrospective analysis of Medicare data from 2007 to 2008 linked to the Minimum Data Set. During the study period, 53,805 (77%) NH residents with dementia used at least one DAP each month. Sixty-seven percent of residents with dementia used Anticholinergic Cognitive Burden Scale (ACBS) level 1 DAPs, 3% used level 2 DAPs, and 31% used level 3 DAPs. Thirteen percent of NH residents with dementia concomitantly used ACBS levels 2 or 3 DAPs and AChEIs. This study sheds new light on the prevalence of DAP use and concomitant use of DAPs and AChEIs among NH residents with dementia. Clinicians should consider alternatives with lower anticholinergic effects, particularly in patients already taking DAPs.

Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

PurposeAcetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered 11C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands.MethodsThe distribution of 11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight = 220±8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of 11C-DNP (45.0±10.7 MBq). The whole-body distribution of the 11C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs.ResultsThe PET analysis using Vt showed that the adrenal glands had the 2nd highest level of 11C-DNP in the body (following the liver) (13.33±1.08 and 19.43±1.29 ml/cm3, respectively), indicating that the distribution of 11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9±1.6, 83.1±3.0, and 38.5±8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands.ConclusionsWe demonstrated the whole-body distribution of 11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of 11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

Antidementia drug use among community-dwelling individuals with Alzheimer’s disease in Finland

The objective of this study was to investigate the prevalence of acetylcholinesterase inhibitor (AChEI) and memantine use, duration of treatment, concomitant use of these drugs, and factors associated with the discontinuation of AChEI therapy during 2006–2009. We utilized data from a nationwide sample of community-dwelling individuals with a clinically verified Alzheimer’s disease diagnosed during the year 2005 (n=6858) as a part of the MEDALZ-2005 study. During the 4-year follow-up, 84% used AChEI and 47% used memantine. Altogether, 22% of the sample used both drugs concomitantly. The median duration of the first AChEI use period was 860 (interquartile range 295–1458) days and 1103 (interquartile range 489–1487) days for the total duration of AChEI use. Although 20% of the AChEI users discontinued the use during the first year, over half of them restarted later. The risk of discontinuation was higher for rivastigmine [hazard ratio 1.34 (confidence interval 1.22–1.48)] and galantamine users [hazard ratio 1.23 (confidence interval 1.15–1.37)] compared with donepezil users in the adjusted model. In conclusion, median time for AChEI use was over 3 years and every fifth Alzheimer’s disease patient used AChEI and memantine concomitantly during the follow-up. The low rate of discontinuation is consistent with the Finnish Care Guideline but in contrast to the results reported from many other countries.

Duration of therapy with acetylcholinesterase inhibitors in patients with mild-to-moderate Alzheimer's disease as reported in the literature.

To review the literature regarding the treatment duration of acetylcholinesterase inhibitor (AChEI) therapy for mild-to-moderate Alzheimer's disease (AD) patients. A literature search was performed using MEDLINE/PubMed, Embase, International Pharmaceutical Abstracts, and Clinical Key (all through May 31, 2013) with the search terms Alzheimer's disease, cholinesterase inhibitors, dementia, treatment and duration, with limits to human, clinical, and observational trials, and English studies; no limits were placed on publication dates. Based on the study selection, 40 studies were identified. The criteria for studies reviewed focused on the duration of AChEIs in patients with mild or moderate AD for a minimum of one year. Based on the selection criteria, five studies were reviewed. These studies evaluated the cognitive efficacy of AChEI after "long-term" (1.5 years) treatment in the clinical trial with follow-up noted in the observational studies of a maximum of "greater than 3 years" (up to 7 years). Cognitive decline was measured by changes in Mini-Mental State Exam scores or Alzheimer's Disease Assessment Scale scores. There were no studies identified that suggested an optimal duration of AChEI therapy for AD patients. Based on the trials reviewed, the duration for AChEI use is very patient-specific; therefore, risk versus benefit of therapy needs to be evaluated regularly in AD patients. The maximum mean duration of follow-up in the clinical study analyzed here was only 1.5 years and observational studies with follow-up "greater than 3 years." Further long-term research is needed.

Duration of Therapy with Acetylcholinesterase Inhibitors in Patients with Mild-to-Moderate Alzheimer's Disease as Reported in the Literature

To review the literature regarding the treatment duration of acetylcholinesterase inhibitor (AChEI) therapy for mild-to-moderate Alzheimer's disease (AD) patients.A literature search was performed using MEDLINE/PubMed, Embase, International Pharmaceutical Abstracts, and Clinical Key (all through May 31, 2013) with the search terms Alzheimer's disease, cholinesterase inhibitors, dementia, treatment and duration, with limits to human, clinical, and observational trials, and English studies; no limits were placed on publication dates.Based on the study selection, 40 studies were identified. The criteria for studies reviewed focused on the duration of AChEIs in patients with mild or moderate AD for a minimum of one year.Based on the selection criteria, five studies were reviewed. These studies evaluated the cognitive efficacy of AChEI after "long-term" (1.5 years) treatment in the clinical trial with follow-up noted in the observational studies of a maximum of "greater than 3 years" (up to 7 years). Cognitive decline was measured by changes in Mini-Mental State Exam scores or Alzheimer's Disease Assessment Scale scores. There were no studies identified that suggested an optimal duration of AChEI therapy for AD patients.Based on the trials reviewed, the duration for AChEI use is very patient-specific; therefore, risk versus benefit of therapy needs to be evaluated regularly in AD patients. The maximum mean duration of follow-up in the clinical study analyzed here was only 1.5 years and observational studies with follow-up "greater than 3 years." Further long-term research is needed.

Trends in the prevalence of antipsychotic drug use among patients with Alzheimer's disease and other dementias including those treated with antidementia drugs in the community in the UK: a cohort study

ObjectiveTo investigate the pattern and trends of use of antipsychotics, antidepressants, hypnotics and anxiolytics in Alzheimer's disease and other dementias and in patients treated with antidementia medications.DesignCohort study with dementia...