Background: Quality of life (QoL) in dementia is a complex construct and factors that predict QoL ratings are unclear. We designed this study to determine: (1) the agreement in QoL ratings between community-dwelling patients with mild to moderate dementia and family carers; and (2) the factors associated with self-reported and two types of carer-reported QoL ratings: carer–carer perspective and carer–patient perspective.

Methods: A cross-sectional study was carried out of 80 community-dwelling patients with the diagnosis of probable Alzheimer's disease (AD) of mild or moderate severity according to NINCDS-ADRD criteria, and their 80 family carers. The QoL-AD was the primary outcome measure. We collected patients’ self-reported QoL ratings and two types of carer-reported QoL ratings: carer–patient and carer–carer perspectives. Explanatory variables included demographics, lifestyle, and clinical information from patients and carers, along with cognition, awareness, psychopathology, burden-of-care, and functionality in daily life. Bland-Altman plots guided the interpretation of agreement by visualizing the distribution of all the ratings. Univariate and multivariate regression analyses were conducted to examine the contribution of candidate explanatory factors.

Results: Patients and their carers showed good agreement in their QoL ratings, although the total scores of carers (regardless of perspective) were lower than the scores of patients. Depression, insight and use of anti-dementia agents were associated with QoL self-ratings, whereas cognitive function was directly associated and depression inversely associated with carers’ QoL ratings.

Conclusion: Mild to moderate community-dwelling AD patients and their carers (with different perspectives) agree within an acceptable range in QoL ratings but the ratings are driven by different factors, and consequently are not interchangeable but complementary. They provide valuable information when used separately, not in a composite score.

Background: Behavioral and psychological symptoms, such as verbal or physical aggression, aberrant motor behaviors, psychotic symptoms, anxiety, depressive symptoms and apathy are common among people with dementia. The aim of the present study was to compare the one-week prevalence of behavioral and psychological symptoms and psychotropic drug treatment among people with cognitive impairment living in institutional care, in two large, comparable samples from 2000 and 2007.

Methods: A comparison was made between two cross-sectional samples, collected in 2000 and 2007, comprising 4054 participants with cognitive impairment living in geriatric care units in the county of Västerbotten, Sweden. The Multi-Dimensional Dementia Assessment Scale (MDDAS) was used to assess cognitive impairment and behavioral and psychological symptoms. The use of psychotropic drugs was recorded.

Results: Between 2000 and 2007, 15 out of 39 behavioral or psychological symptoms had become less common and no symptoms had become more common, after controlling for demographic changes. Four out of six behaviors within the cluster of aggressive behaviors had declined in prevalence. Patients prescribed anti-dementia drugs increased from 5.1% to 18.0% and antidepressant drug use increased from 43.2% to 49.1%, while anxiolytic, hypnotic, sedative and antipsychotic drug use remained largely unchanged.

Conclusion: The prevalence of many behavioral symptoms had declined from 2000 to 2007, and among these changes, the decline in aggressive behaviors probably has the greatest clinical impact.

There is considerable evidence that pro-cholinergic agents can cause depressed mood. However, there are also published case reports of a rare association between cholinesterase inhibitors and mood elevation in patients with pre-existing major functional psychiatric disorders, or organic disorders other than dementia. This report adds to the literature by describing a case of mood elevation in a patient without pre-existing psychiatric disorder.

Background: Cholinesterase inhibitors (ChEIs) are being used for increasingly long periods of time, even in patients with severe Alzheimer's disease. Because there is little data to help clinicians to decide on when it is safe and appropriate to discontinue ChEIs after long-term use, practices may vary widely.

Methods: An internet-based survey was undertaken of Canadian dementia experts (geriatric psychiatrists, neurologists, geriatricians) involved in clinical trial research. Recommendations for ChEI discontinuation were determined based on responses to questions dealing with patient/caregiver preference, administrative considerations, effectiveness, and adverse events.

Results: There was reasonable consensus that ChEIs should be discontinued based on patient and caregiver preference, and in the presence of severe bothersome adverse events. There was much less consensus on issues related to effectiveness – in particular, what constitutes greater than expected decline. There was a general reluctance to rely on any single measure of cognition, function and/or behavior, and in particular, the MMSE was seen as unhelpful for making decisions about discontinuation.

Conclusion: Recommendations for discontinuing ChEIs after long-term use from a survey of dementia experts are presented. Ideally, clinical practice guidelines based on controlled discontinuation trials are needed.

Background: This study sought to examine the trends in the prescribing of subsidized and unsubsidized cognition enhancing drugs (CEDs) in Australia over five years from 2002 to 2007. Subsidized cholinesterase inhibitor medication could be prescribed to people with mild to moderate Alzheimer's disease (AD) once a specialist physician had confirmed this diagnosis. Memantine was available for use in moderately severe AD but not subsidized.

Methods: We analyzed the Medicare Australia and Drug Utilisation Sub-Committee databases for CED prescription data, 2002–2007, by gender, age and prescriber class. Aggregated prescription data for each medication were converted to defined daily doses (DDD) per 1000 persons per day using national census data.

Results: There were 1,583,667 CED prescriptions dispensed during the study period. CED use increased 58% from 0.91 to 1.56 DDD/1000 persons/day between 2002 and 2007. Peak use was in those aged 85–89 years. Age-adjusted utilization was slightly higher in females than males. Donepezil was the most widely used CED (66%), followed by galantamine (27%) then memantine (4%). General practitioners prescribed the majority of CEDs. Geriatricians exhibited a greater preference for galantamine than other prescribers. CED dispensing peaked towards the end of each calendar year, reflecting stockpiling by patients under the influence of a federal safety net subsidy.

Conclusions: Despite subsidized access to CEDs in Australia, only a minority of people with AD was prescribed these drugs during the period of the study. It is likely that the combination of complex prescribing rules and negative perceptions about efficacy or cost-effectiveness might have contributed to these findings.

Objectives: Since 2002, the treatment with cholinesterase inhibitors (CHEIs) for Alzheimer's disease (AD) has been paid for by the public health system of the Brazilian Ministry of Health for any patient that fulfills clinical criteria established by an evidence-based guideline developed and published by the Ministry. The aim of this study was to evaluate compliance of prescription patterns to the national guideline for use of CHEIs’ in the southern Brazilian state of Rio Grande do Sul.

Methods: We created a regional expert-committee reference center to review all prescriptions of CHEIs and to send feedback to physicians whenever prescriptions without compliance to the guideline were noted. One thousand three hundred ninety-nine (1,399) CHEI prescriptions presented to the public health system from 2005 to 2007 were evaluated by an expert team of neurologists and psychiatrists. Clinical history, performance on mental status screening by Mini Mental State Examination (MMSE), Clinical Dementia Rating scale (CDR), laboratory results, and neuroimaging findings were evaluated in relation to the adherence to the national guideline's recommendations. If the prescription was rejected because of lack of adherence to the criteria of the guideline, a written response was sent by the expert committee to physicians concerning the request.

Results: The majority of the requests (n = 1,044; 75 percent) did not meet the AD guideline's criteria, either for diagnosis or for treatment, and were not granted. A diagnostic mistake was evident in 64.3 percent of cases. Findings of vascular or Parkinson's dementia or severe AD were the main reasons for rejection. Rivastigmine was the most prescribed cholinesterase inhibitor, used in 86 percent of cases. Of note was the reduction in the number of CHEIs prescriptions in the years following this intervention.

Conclusions: The public health strategy of using expert-review of prescriptions and their compliance to national guideline revealed a low rate of rational use of CHEIs for dementia. Such a strategy is relevant for protecting patients from unproven medical interventions and for reducing waste of resources.

Background: Delirium is common in the elderly and is associated with high mortality and negative health outcomes. Reduced activity in the cholinergic system has been implicated in the pathogenesis of delirium. Cholinesterase inhibitors, which increase cholinergic activity, may therefore be beneficial in the treatment of delirium.

Methods: This is a double-blind, placebo-controlled randomized pilot study of the treatment of delirium with a cholinesterase inhibitor of patients admitted to hospital medical wards. Patients over the age of 65 years were identified as having delirium by the Confusion Assessment Method (CAM). Patients with delirium were randomized to receive rivastigmine 1.5 mg once a day increasing to 1.5 mg twice a day after seven days or an identical placebo (two tablets after seven days).

Results: Fifteen patients entered the trial; eight received rivastigmine and seven received placebo. All of the rivastigmine group, but only three of the placebo group, were negative for delirium on the CAM when they left the study and eventually discharged home. There was no significant difference in the duration of delirium between the two groups (rivastigmine group 6.3 days versus placebo group 9.9 days, p = 0.5, 95% confidence interval −15.6–8.4).

Conclusions: The numbers of patients who screened positive for delirium was very small and as a result the sample size was too small to make any meaningful inferences about treatment of delirium. Despite the small numbers included in the study, there are some indicators that rivastigmine may be safe and effective in treating delirium.

Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire from 375 caregivers in Montreal. Sixty-four per cent of caregivers responded (n = 201), and most (≥59%) were willing to continue treatment if persons with Alzheimer's disease suffered from weight loss or loss of appetite. However, most (≥53%) were not willing to continue treatment in the event of headache, dizziness, nausea, diarrhea, vomiting, drop in blood pressure, insomnia, muscle cramps, or stomach bleeding. The use of cholinesterase inhibitors by persons with Alzheimer's disease was positively associated with caregivers' willingness to accept greater numbers of adverse effects (adjusted relative risk = 1.97; 95% CI = 1.11 to 3.61). Caregivers appear to make a risk–benefit assessment when they decide whether or not care-recipients should continue pharmacotherapy in the event of adverse effects.

Background: This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors (SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimer's disease (AD) living at home.

Methods: The study was conducted in two different outpatient neurological clinics. 338 patients with probable AD were treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinician's judgment and were observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1), three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated with SSRIs).

Results: At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change −0.8 ± 2.3 vs 0.04 ± 2.9; p = 0.02) and patients depressed and treated with SSRI (mean change −0.8 ± 2.3 vs 0.1 ± 2.5; p = 0.03).

Conclusions: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition.

Background: The study aim was to conduct a systematic review of the evidence from randomized, placebo controlled trials related to the efficacy of donepezil, rivastigmine and galantamine in the treatment of behavioral and psychological symptoms of Alzheimer's disease.

Methods: Electronic database searches of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were carried out using multiple search terms. Articles included were original publications of randomized, placebo-controlled trials of monotherapy of donepezil, rivastigmine or galantamine that reported a behavioral outcome measure.

Results: 14 studies were identified that matched inclusion criteria. Nine were of donepezil, three of galantamine and two of rivastigmine. Median study treatment length was 24 weeks (range 12–170). Most studies used the Neuropsychiatric Inventory as a behavioral outcome measure although three used specific scales for either agitation or apathy. Four studies were specifically designed to assess behavioral outcomes whilst in the majority of studies behavioral outcomes were only secondary measures. Three studies found statistically significant, albeit modest, differences in the change of NPI total score between drug and placebo. The interpretation of the results of many studies is limited by methodological considerations, including generally low NPI scores at baseline and the investigation of behavioral and psychological symptoms of dementia (BPSD) as secondary outcomes.

Conclusions: The evidence base regarding the efficacy of cholinesterase inhibitors in BPSD is limited, in part due to methodological considerations. In the absence of alternative safe and effective management options, the use of cholinesterase inhibitors is an appropriate pharmacological strategy for the management of BPSD in Alzheimer's disease.

Six individuals with probable Alzheimer’s disease (AD) participated in a phase 1 study employing a repeated measures, parallel baseline design testing the hypothesis that error-free experience during word production practice combined with an acetyl cholinesterase inhibitor would improve confrontation naming ability. While acetyl cholinesterase inhibitors are safe and delay cognition decline associated with AD, improvement over baseline cognition is less evident; clinically significant cognitive deficits persist and progress. Both animal and clinical research strongly implicate acetylcholine in learning, a form of neuroplasticity. In clinical practice, however, people with AD are given cholinergic medications without concomitant systematic/targeted retraining. In this study six participants with probable AD and taking donepezil participated in targeted word production practice using an errorless learning strategy. Results showed that combining behavioral enrichment training and an acetyl cholinesterase inhibitor resulted in significant improvements in verbal confrontation naming of trained items for three of six participants. Differences in baseline dementia severity, living conditions, and medications may have influenced the training response. Detection of substantial treatment effects in 50% of subjects suggests further language treatment studies in AD in combination with an acetyl cholinesterase inhibitor are warranted and provide useful information on inclusion/exclusion criteria for use in subsequent studies. (JINS, 2009, 15, 311–322.)