Ian Maidment

Anticholinergic medication use and cognitive impairment in the older population:the medical research council cognitive function and ageing study

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative.

The cognitive impact of anticholinergics:a clinical review

Context: The cognitive side effects of medications with anticholinergic activity have been documented among older adults in a variety of clinical settings. However, there has been no systematic confirmation that acute or chronic prescribing of such medications lead to transient or permanent adverse cognitive outcomes. Objective: Evaluate the existing evidence regarding the effects of anticholinergic medications on cognition in older adults. Data sources: We searched the MEDLINE, OVID, and CINAHL databases from January, 1966 to January, 2008 for eligible studies. Study selection: Studies were included if the anticholinergic activity was systematically measured and correlated with standard measurements of cognitive performance. Studies were excluded if they reported case studies, case series, editorials, and review articles. Data extraction: We extracted the method used to determine anticholinergic activity of medications and its association with cognitive outcomes. Results: Twenty-seven studies met our inclusion criteria. Serum anticholinergic assay was the main method used to determine anticholinergic activity. All but two studies found an association between the anticholinergic activity of medications and either delirium, cognitive impairment or dementia. Conclusions: Medications with anticholinergic activity negatively affect the cognitive performance of older adults. Recognizing the anticholinergic activity of certain medications may represent a potential tool to improve cognition.

Impact of anticholinergics on the aging brain: a review and practical application

Objective: in an effort to enhance medication prescribing for older adults and reduce the burden of cognitive impairment, this paper reviews the literature regarding the negative impact of anticholinergics on cognitive function and provides clinicians with a practical guidance for anticholinergic use in older adults. Methods: a Medline search identified studies evaluating the use of anticholinergics and the relationship between anticholinergics and cognitive impairment. Results: prescribing anticholinergics for older adults leads to acute cognitive impairment and, possibly, chronic cognitive deficits. Assessing anticholinergic burden with a simple scale may represent a useful noninvasive tool to optimize geriatric pharmacotherapy. Conclusion: more studies are needed to validate the Anticholinergic Cognitive Burden scale and establish therapeutic guidelines in the presence of cognitive anticholinergic adverse effects.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review

OBJECTIVES to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes. DESIGN electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible. RESULTS forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good. CONCLUSION medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes.

Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial.

Background Agitation in Alzheimer’s disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD. Methods and Findings We recruited 153 participants with AD and clinically significant agitation from care-homes or hospitals for a double-blind randomised-controlled trial and 149 people started the trial of memantine versus placebo. The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes were: 12 weeks CMAI; 6 and 12 weeks Neuropsychiatric symptoms (NPI), Clinical Global Impression Change (CGI-C), Standardised Mini Mental State Examination, Severe Impairment Battery. Using a mixed effects model we found no significant differences in the primary outcome, 6 weeks CMAI, between memantine and placebo (memantine lower −3.0; −8.3 to 2.2, p = 0.26); or 12 weeks CMAI; or CGI-C or adverse events at 6 or 12 weeks. NPI mean difference favoured memantine at weeks 6 (−6.9; −12.2 to −1.6; p = 0.012) and 12 (−9.6; −15.0 to −4.3 p = 0.0005). Memantine was significantly better than placebo for cognition. The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD. Conclusions Memantine did not improve significant agitation in people with in moderate-to-severe AD. Future studies are urgently needed to test other pharmacological candidates in this group and memantine for neuropsychiatric symptoms. Trial Registration ClinicalTrials.gov NCT00371059 Trial Registration International Standard Randomised Controlled Trial 24953404

Efficacy of Memantine on Behavioral and Psychological Symptoms Related to Dementia: A Systematic Meta-Analysis

Background: The behavioral and psychological symptoms related to dementia (BPSD) are difficult to manage and are associated with adverse patient outcomes. Objective: To systematically analyze the data on memantine in the treatment of BPSD. Methods: We searched MEDLINE, EMBASE, Pharm-line, the Cochrane Centre Collaboration, www.clinicaltrials.gov, www.controlled-trials.com, and PsycINFO (1966–July 2007). We contacted manufacturers and scrutinized the reference sections of articles identified in our search for further references, including conference proceedings. Two researchers (IM and CF) independently reviewed all studies Identified by the search strategy. We Included 6 randomized, parallel-group, double-blind studies that rated BPSD with the Neuropsychiatric Inventory (NPI) in our meta-analysis. Patients had probable Alzheimers disease and received treatment with memantine for at least one month. Overall efficacy of memantine on the NPI was established with a t-test for the average difference between means across studies, using a random effects model. Results: Five of the 6 studies identified had NPI outcome data. In these 5 studies, 868 patients were treated with memantine and 882 patients were treated with placebo. Patients on memantine improved by 1.99 on the NPI scale (95% CI –0.08 to –3.91: p = 0.041) compared with the placebo group. Conclusions: Initial data appear to indicate that memantine decreases NPI scores and may have a role in managing BPSD. However, there are a number of limitations with the current data; the effect size was relatively small, and whether memantine produces significant clinical benefit is not dear.

The impact of anticholinergic burden in Alzheimer's Dementia-the Laser-AD study

OBJECTIVE to examine the effect of medications with anticholinergic effects on cognitive impairment and deterioration in Alzheimers dementia (AD). METHODS cognitive function was measured at baseline and at 6- and 18-month follow-up using the Mini-Mental State Exam (MMSE), the Severe Impairment Battery (SIB) and the Alzheimers Disease Assessment Battery, Cognitive subsection (ADAS-COG) in a cohort study of 224 participants with AD. Baseline anticholinergic Burden score (ABS) was measured using the Anticholinergic Burden scale and included all prescribed and over the counter medication. RESULTS the sample was 224 patients with Alzheimers dementia and 71.4% were women. Their mean age was 81.0 years [SD 7.4 (range 55-98)]. The mean number of medications taken was 3.6 (SD 2.4) and the mean anticholinergic load was 1.1 (SD 1.4, range 0-7). The total number of drugs taken and anticholinergic load correlated (rho = 0.44; P < 0.01). There were no differences in MMSE and other cognitive functioning at either 6 or 18 months after adjusting for baseline cognitive function, age, gender and use of cholinesterase inhibitors between those with, and those without high anticholinergenic load. CONCLUSIONS medications with anticholinergic effect in patients with AD were not found to effect deterioration in cognition over the subsequent 18 months. Our study did not support a continuing effect of these medications on people with AD who are established on them.

Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: A meta-analysis

Objective To determine the efficacy of cholinesterase inhibitors (ChEIs) in improving the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer’s disease (AD). Data sources We searched MEDLINE, Cochrane Registry, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1966 to 2007. We limited our search to English Language, full text, published articles and human studies. Data extraction We included randomized, double-blind, placebo-controlled trials evaluating the efficacy of donepezil, rivastigmine, or galantamine in managing BPSD displayed by AD patients. Using the United States Preventive Services Task Force (USPSTF) guidelines, we critically appraised all studies and included only those with an attrition rate of less than 40%, concealed measurement of the outcomes, and intention to treat analysis of the collected data. All data were imputed into pre-defined evidence based tables and were pooled using the Review Manager 4.2.1 software for data synthesis. Results We found 12 studies that met our inclusion criteria but only nine of them provided sufficient data for the meta-analysis. Among patients with mild to severe AD and in comparison to placebo, ChEIs as a class had a beneficial effects on reducing BPSD with a standard mean difference (SMD) of −0.10 (95% confidence interval [CI]; −0.18, −0.01) and a weighted mean difference (WMD) of −1.38 neuropsychiatry inventory point (95% CI; −2.30, −0.46). In studies with mild AD patients, the WMD was −1.92 (95% CI; −3.18, −0.66); and in studies with severe AD patients, the WMD was −0.06 (95% CI; −2.12, +0.57). Conclusion Cholinesterase inhibitors lead to a statistical significant reduction in BPSD among patients with AD, yet the clinical relevance of this effect remains unclear.

The Use of Antidepressants to Treat Attention Deficit Hyperactivity Disorder in Adults

There is increasing evidence that children continue to experience attention deficit hyperactivity disorder (ADHD) symptoms into adult life. The two main treatments for ADHD are antidepressants and stimulants. Here, the effectiveness data relating to the use of antidepressants in adults with ADHD are reviewed. Four controlled and six open studies were identified. Although, there is only limited data currently available, antidepressants may offer an effective therapy for adult ADHD. Controlled trials have studied desipramine, atomoxetine and bupropion, with most evidence supporting the efficacy of desipramine. The initial data indicate that atomoxetine is less effective than desipramine. The efficacy of bupropion is unclear. Initial published open data suggest a response rate of 50-78% with venlafaxine. Controlled studies are required to confirm this efficacy. Most of the present data are short-term, therefore long-term effectiveness data are required.

A pharmacy led program to review anti-psychotic prescribing for people with dementia

BackgroundAnti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics.MethodsThis project was conducted within primary care in Medway Primary Care Trust (PCT) in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people with dementia prescribed anti-psychotics. Second, a trained specialist pharmacist conducted targeted clinical medication reviews in people with dementia initiated on anti-psychotics by primary care, identified by the data search.ResultsData were collected from 59 practices. One hundred and sixty-one (15.3%) of 1051 people on the dementia register were receiving low-dose anti-psychotics. People with dementia living in residential homes were nearly 3.5 times more likely to receive an anti-psychotic [25.5% of care home residents (118/462) vs. 7.3% of people living at home (43/589)] than people living in their own homes (p < 0.0001; Fisher’s exact test). In 26 practices there was no-one on the dementia register receiving low-dose anti-psychotics.Of the 161 people with dementia prescribed low-dose anti-psychotics, 91 were receiving on-going treatment from local secondary care mental health services or Learning Disability Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or the dosage was reduced, in 43 instances (61.4%) following the pharmacy-led medication review.ConclusionsIn total 15.3% of people on the dementia register were receiving a low-dose anti-psychotic. However, such data, including the recent national audit may under-estimate the usage of anti-psychotics in people with dementia. Anti-psychotics were used more commonly within care home settings. The pharmacist-led medication review successfully limited the prescribing of anti-psychotics to people with dementia.