Acetylcholinesterase Inhibitors Therapy Research Articles

Potential cardioprotective effects of acetylcholinesterase inhibitors in patients with Alzheimer's disease

Abstract Background In patients with mild to moderate Alzheimer's disease (AD), acetylcholinesterase inhibitors (AChE-I) are commonly employed to improve cognitive function. They increase the amount of acetylcholine (ACh) in the neuronal synapses, but bradycardia, cardiac electrical conduction blocks and hypotension due to muscarinic M2 receptor stimulation are potential side effects. However, whether these "side effects" could play a potential protective effect on cardiovascular (CV) events is not yet well defined. Purpuses To evaluate potential beneficial cardiac effects of AChE-Is in patients with AD, in terms of reduction of major adverse cardiovascular events (MACEs). Methods We conducted a retrospective, monocentric, observational cohort study in patients referred to our hospital. Two groups were considered: the interventional group included AD patients treated with AChE-I. The control group enrolled a cohort of subjects matched for age and comorbidities, recruited between caregivers of intervention group subjects that were cognitively unimpaired and not taking AchE-I. The primary endpoint was a composite of hospitalization for heart failure (HF), non-fatal acute myocardial infarction (AMI), myocardial revascularization, hospitalization for cardiovascular (CV) causes, cardiovascular mortality and occurrence of stroke and/or TIA during total 5 year follow-up period (MACEs). Secondary endpoints were each individual component of the primary end point, total deaths, non-cardiovascular death and incidence of pacemaker implant. Results 221 AD patients treated with AChE-I (91 with Donepezil, 130 with Rivastigmine) were included in intervention group and 221 non-AD patients in control group. Groups were homogeneous in terms of age, gender and main cardiovascular risk factors, except for family history of cardiovascular diseases (CVD), which was more frequent in control group. During a median follow-up of 3.1 years the primary endpoint occurred in 24 patients in intervention group (2.1 per 100 patient-years) compared to 56 patients in the control group (5.0 per 100 patient-years). Therefore, AChE-I therapy resulted a protective factor from primary endpoint (HR 0.48, 95% CI 0.24-0.95; p= 0.036). Even not significant, the difference was mainly driven by myocardial revascularization (3.2% in intervention group vs 6.8% in controls) and hospitalization for heart failure (4.5% in intervention group vs 14.5% in controls). Non-CVD mortality was significantly higher in treatment group (13,6% in intervention group vs 2,7% in controls). No significant difference was observed between groups in terms of other secondary outcomes. Conclusions Among patients with AD, use of AChE-I may be protective for CV outcomes, especially reducing HF hospitalisation and myocardial revascularization.Kaplan-Meier of cumulative MACEsNumber of Event/Years

Psychiatric Adverse Events of Acetylcholinesterase Inhibitors in Alzheimer's Disease and Parkinson's Dementia: Systematic Review and Meta-Analysis.

The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia. While these drugs are known to induce classic cholinergic adverse events such as diarrhea, their potential to cause psychiatric adverse events has yet to be thoroughly examined. We sought to determine the risk of psychiatric adverse events associated with the use of AChEIs through a systematic review and meta-analysis of double-blind randomized controlled trials involving patients with Alzheimer's dementia and Parkinson's dementia. A total of 48 trials encompassing 22,845 patients were included in our analysis. Anorexia was the most commonly reported psychiatric adverse event, followed by agitation, insomnia, and depression. Individuals exposed to AChEIs had a greater risk of experiencing appetite disorders, insomnia, or depression compared with those who received placebo (anorexia: odds ratio [OR] 2.93, 95% confidence interval [CI] 2.29-3.75; p < 0.00001; decreased appetite: OR 1.93, 95% CI 1.33-2.82; p=0.0006; insomnia: OR 1.55, 95% CI 1.25-1.93; p < 0.0001; and depression: OR 1.59, 95% CI 1.23-2.06, p=0.0004). Appetite disorders were also more frequent with high-dose versus low-dose therapy. A subgroup analysis revealed that the risk of insomnia was higher for donepezil than for galantamine. Our findings suggest that AChEI therapy may negatively impact psychological health, and careful monitoring of new psychiatric symptoms is warranted. Lowering the dose may resolve some psychiatric adverse events, as may switching to galantamine in the case of insomnia. The study was pre-registered on PROSPERO (CRD42021258376).

Acetyl-cholinesterase-inhibitors slow cognitive decline and decrease overall mortality in older patients with dementia

We evaluated the effect of Acetyl-cholinesterase-inhibitors (AChEIs) on cognitive decline and overall survival in a large sample of older patients with late onset Alzheimer’s disease (LOAD), vascular dementia (VD) or Lewy body disease (LBD) from a real world setting. Patients with dementia enrolled between 2005 and 2020 by the "Alzheimer's Disease Research Centers" were analysed; the mean follow-up period was 7.9 years. A 1:1 propensity score matching was performed generating a cohort of 1.572 patients (786 treated [AChEIs +] and 786 not treated [AChEIs-] with AChEIs. The MMSE score was almost stable during the first 6 years of follow up in AChEIs + and then declined, while in AChEIs− it progressively declined so that at the end of follow-up (13.6 years) the average decrease in MMSE was 10.8 points in AChEIs- compared with 5.4 points in AChEIs + (p < 0.001). This trend was driven by LOAD (Δ-MMSE:−10.8 vs. −5.7 points; p < 0.001), although a similar effect was observed in VD (Δ-MMSE:−11.6 vs. −8.8; p < 0.001). No effect on cognitive status was found in LBD. At multivariate Cox regression analysis (adjusted for age, gender, dependency level and depression) a strong association between AChEIs therapy and lower all-cause mortality was observed (H.R.:0.59; 95%CI: 0.53–0.66); this was confirmed also in analyses separately conducted in LOAD, VD and LBD. Among older people with dementia, treatment with AChEIs was associated with a slower cognitive decline and with reduced mortality, after a mean follow-up of almost eight years. Our data support the effectiveness of AChEIs in older patients affected by these types of dementia.

Long-Term Effect of Acetylcholinesterase Inhibitors on the Dorsal Attention Network of Alzheimer's Disease Patients: A Pilot Study Using Resting-State Functional Magnetic Resonance Imaging.

BackgroundAlzheimer’s disease (AD) is the most common condition of all neurodegenerative diseases and is characterized by various cognitive dysfunctions. Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed the physiological dynamics of functionally connected brain networks, which are called resting-state networks (RSNs). Associations between impairments of RSNs and various neuropsychiatric diseases, such as AD, have been reported. Acetylcholinesterase inhibitors (AChEIs) have been used as a pharmacological treatment for mild-to-moderate moderate AD, and short-term improvements in cognitive functions and RSNs in restricted areas have been reported.ObjectiveWe aimed to characterize AChEI-related RSN changes by acquiring two sets of rs-fMRI data separated by approximately 3 to 6 months.MethodsSeventeen patients with AD and nine healthy subjects participated in this study. Independent component analysis was performed on the rs-fMRI data of AChEI-responsive and non-responsive AD patients, stratified according to change in Mini-Mental State Examination (MMSE) scores after 3 to 6 months of AChEI therapy. In addition, a region of interest-based analysis of the rs-fMRI data before therapy was performed to explore the functional connectivity (FC) changes associated with AchEI therapy.ResultsResponders showed a significantly greater increase in MMSE scores, especially for orientation for time, than that of non-responders following AChEI therapy. A subtraction map of MMSE score differences (responders minus non-responders) in the independent component analysis revealed higher FC of the dorsal attention network in responders compared with that in non-responders. Moreover, in the region of interest analysis of untreated status data, the dorsal attention network showed significant negative FC with the right planum temporale, which belongs to the ventral attention network, proportional to MMSE score change.ConclusionThe negative correlation of the FC of the dorsal attention network and right planum temporale before AChEI therapy and MMSE score change may be a biomarker of the therapeutic effect of AChEIs for AD.

Association between human paraoxonase 2 protein and efficacy of acetylcholinesterase inhibiting drugs used against Alzheimer's disease.

Serum Paraoxonase 2 (PON2) level is a potential biomarker owing to its association with a number of pathophysiological conditions such as atherosclerosis and cardiovascular disease. Since cholinergic deficiency is closely linked with Alzheimer’s disease (AD) progression, acetylcholinesterase inhibitors (AChEIs) are the treatment of choice for patients with AD. However, there is a heterogenous response to these drugs and mostly the subjects do not respond to the treatment. Gene polymorphism, the simultaneous occurrence of two or more discontinuous alleles in a population, could be one of the important factors for this. Hence, we hypothesized that PON2 and its polymorphic forms may be hydrolyzing the AChEIs differently, and thus, different patients respond differently. To investigate this, two AChEIs, donepezil hydrochloride (DHC) and pyridostigmine bromide (PB), were selected. Human PON2 wildtype gene and four mutants, two catalytic sites, and two polymorphic sites were cloned, recombinantly expressed, and purified for in vitro analysis. Enzyme activity and AChE activity were measured to quantitate the amount of DHC and PB hydrolyzed by the wildtype and the mutant proteins. Herein, PON2 esterase activity and AChE inhibitor efficiency were found to be inversely related. A significant difference in enzyme activity of the catalytic site mutants was observed as compared to the wildtype, and subsequent AChE activity showed that esterase activity of PON2 is responsible for the hydrolysis of DHC and PB. Interestingly, PON2 polymorphic site mutants showed increased esterase activity; therefore, this could be the reason for the ineffectiveness of the drugs. Thus, our data suggested that the esterase activity of PON2 was mainly responsible for the hydrolysis of AChEI, DHC, and PB, and that might be responsible for the variation in individual response to AChEI therapy.

The Pupil Diameter as a Possible Indicator of Neurodegenerative Diseases and Response to Acetylcholinesterase Inhibitors Therapy: In-Depth Measurements Following Topical Administration of Tropicamide and Pilocarpine.

The aim of this study is to assess whether pupillary modifications following ocular anticholinergic and cholinergic drugs can identify subjects with neurodegenerative diseases from early stages. 51 subjects were divided into 3 groups, according to different neurodegenerative diseases, and compared with a control group of 10 patients. Pupil diameter has been measured at different times after topical administration of tropicamide 0.01% in the right eye. Then, topical administration of pilocarpine 0.06% has been performed, followed by pupillary constriction measurement. Pupillary response rates were stratified according to acetylcholinesterase inhibitors intake. Observed mydriasis and pupillary constriction was similar in all study groups at all evaluation times. Patients without acetylcholinesterase inhibitors intake presented greater mydriasis. Although it was not possible to observe significant differences among groups in terms of pupillary response, the analysis of pupillary features may become an useful tool to detect efficacy of acetylcholinesterase inhibitors.

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.

Cardiovascular Outcomes of Cholinesterase Inhibitors in Individuals with Dementia: A Meta-Analysis and Systematic Review.

To evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementia DESIGN: Systematic review and meta-analysis. Two authors independently searched major electronic databases from inception until June 17, 2017, for longitudinal (without a control group) and cohort (with a control group) studies reporting CV outcomes in relation to AChEIs. Randomized controlled trials were excluded because they included relatively healthy subjects. Individuals with dementia and controls. Changes in CV parameters were summarized using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Event rates were used to assess incidence of hypertension and bradycardia. Incidence of CV events in demented patients versus in healthy controls were compared using hazard ratios (HRs). Of 4,588 initial hits, 31 studies including 258,540 individuals with dementia and 2,246,592 controls were analyzed. In longitudinal and open-label studies, AChEIs were associated with a significantly greater incidence of hypertension (n=1,573, 4%, 95% CI=2-8%, I2 =47%) and bradycardia (n=13,703, 2%, 95% CI=1-6%, I2 =98%). AChEIs were associated with a decrease in heart rate (SMD=-1.77, 95% CI=-3.58-0.03, I2 =78%) and an increase in PR interval (SMD=0.10, 95% CI=0.008-0.19, I2 =3%) from baseline. During a median follow-up of 116 weeks, AChEIs were associated with a significantly lower risk of CV events (stroke, acute coronary syndrome, CV mortality; HR=0.63, 95% CI=0.45-0.88, I2 =18%), without a significantly greater risk of bradycardic events (HR=1.40, 95% CI=0.76-2.59, I2 =98%). AChEI therapy may be associated with negative chronotropic and hypertensive effects but also with lower risk of CV events.

Cardiovascular effects of drugs used to treat Alzheimer's disease.

Drugs that are used to treat Alzheimer's disease include the acetyl cholinesterase inhibitors (ACHIs) donepezil, rivastigmine and galantamine and the NMDA receptor antagonist memantine. Adverse cardiovascular events with these drugs are very uncommon. However, there is evidence that ACHI therapy is associated with a small but significant increase in the risk of syncope and bradycardia. There are also a few reports that these drugs may occasionally be associated with QT prolongation and torsades de pointes ventricular tachycardia. Adverse cardiovascular effects of ACHIs including syncope and bradycardia are less common than their adverse gastrointestinal effects, but they remain important considerations in susceptible individuals. In contrast, animal studies and some observational studies suggest that ACHIs may reduce myocardial infarction and cardiovascular mortality and have favourable effects on hemodynamics and survival in heart failure. Further research is required to confirm these potential beneficial effects. Little is known about the cardiovascular effects of memantine but there have been reports of bradycardia and reduced cardiovascular survival associated with its use.

Cholinesterase inhibitor use is associated with increased plasma levels of anti-Abeta 1–42 antibodies in Alzheimer's disease patients

Acetyl-cholinesterase inhibitors (AChEI) are drugs frequently prescribed for the treatment of Alzheimer's disease (AD), exerting an effect on cognition, as well as on behavioural and psychological symptoms of dementia and activities of daily living. The efficacy of AChEI may be ascribed not only to the activation of cholinergic transmission, but also to other mechanisms, among which a putative regulation of the immune response has already been hypothesized. In the present study, we evaluated, in a cross-sectional sample of 66 AD patients and 48 healthy controls, the putative influence of AChEI on anti-Abeta 1–42 antibody plasma levels by ELISA assay. AD patients receiving AChEI therapy showed increased plasma levels of anti-Abeta 1–42 antibodies respect to untreated AD patients and antibodies levels similar to those of healthy controls, both before and after normalization by total IgG values. Our results support a potential role of AChEI in the modulation of the immune response against Abeta. We suggest that a strategy aimed at increasing the endogenous response against this peptide might represent an interesting therapeutic target to be further investigated.

A randomized controlled trial of rivastigmine in patients with cognitive impairment no dementia because of cerebrovascular disease

The safety and efficacy of early acetylcholinesterase inhibitors therapy in patients with cognitive impairment no dementia (CIND) after a cerebrovascular accident have not been examined. In this study, we investigated the safety and efficacy of rivastigmine in cognition, particularly executive function in patients with CIND because of cerebrovascular disease. This study was a 24-week, double-blind, randomized, placebo-controlled trial of ischemic stroke patients seen at a tertiary hospital who had cognitive impairment no dementia because of cerebrovascular disease. The intervention was either rivastigmine or placebo up to 9 mg/day. The primary outcome of interest was mean change from baseline in the Ten-Point Clock Drawing and Color Trails 1 and 2. Fifty patients were randomized into rivastigmine (n = 25) and placebo (n = 25) arms. Patients in the rivastigmine group showed statistically significant improvement (1.70 vs 0.13, P = 0.02) on the animal subtask of the verbal fluency measure compared with placebo. There was also a trend (non-significant) towards improvement in Color Trails II. In this pilot study, we demonstrated that rivastigmine was well tolerated in patients with CIND because of cerebrovascular disease and may potentially improve executive functioning.

A RETROSPECTIVE PILOT STUDY ON THE DEVELOPMENT OF COGNITIVE, BEHAVIORAL AND FUNCTIONAL DISORDERS IN A SAMPLE OF PATIENTS WITH EARLY DEMENTIA OF ALZHEIMER TYPE

This pilot study retrospectively analyzes the evolution of cognitive-behavioral symptoms and functional autonomy in a sample of patients with early diagnosis of probable Alzheimer's disease (AD). One hundred patients with early mild cognitive impairment (MCI) were considered and submitted to a multidimensional evaluation: the 53% presented probable AD. These 53 subjects were evaluated for cognitive performance by using the mini mental examination (MMSE), behavioral functions by the neuropsychiatric inventory (NPI) and functional dependence by the activities of daily living (ADL) and the instrumental ADL (IADL) scales at basal time and after 6–12 months. Results were analyzed according to the duration of therapy with acetyl-cholinesterase inhibitors (ACHEI) and to the timing of the beginning with respect to the diagnosis. AD patients treated with ACHEI at the moment of the diagnosis, showed a statistically significant improvement in MMSE (2.7 ± 1.5) after 6 months (p = 0.012) which was maintained even after 12 months. Subjects beginning ACHEI at the visit of 6 months showed a statistically worsened MMSE, even after 6 months of therapy (−2.8 ± 1.7, p = 0.026). We conclude that the timing of administration of ACHEI therapy in mild AD is essential to obtain beneficial effects on cognitive decline.

Treatment of ocular symptoms in myasthenia gravis

The choice between acetyl-cholinesterase inhibitors (AChE-Is) and steroids as symptomatic therapy for ocular symptoms in myasthenia is controversial. Thirty-five patients with myasthenia and ocular symptoms were evaluated by a single investigator. The ocular-quantitative myasthenia gravis (QMG) score was determined at each visit. The longitudinal construct validity of the ocular-QMG was assessed. Treatment epochs on AChE-I therapy alone or on steroids were defined for each patient. Changes in ocular-QMG scores between the start and end of each treatment epoch as well as the proportion of subjects achieving remission of symptoms were documented. The frequency of steroid-induced side effects was documented. The longitudinal construct validity was favorable and comparable to that for the total QMG score. Eight patients were treated with AChE-I therapy alone, 6 were initially treated with AChE-I followed by steroids, and 21 received steroids ab initio. There were 14 epochs of AChE-I treatment and 27 epochs of steroid treatment. The mean improvement in ocular-QMG score was greater during the steroid epoch (3.6 +/- 2.4) than during the AChE-I epoch (1.1 +/- 1.9) (p = 0.0021). Complete resolution of ocular symptoms occurred in 29% of AChE-I treatment epochs and in 70% of steroid treatment epochs. The most common steroid-induced side effects observed were impaired glucose tolerance (67%) and reduced bone mineral density (20%). The ocular-quantitative myasthenia gravis score may be a useful tool for monitoring ocular symptom severity in myasthenia. Steroids appear to be more effective than acetyl-cholinesterase inhibitors. These findings warrant a more formal evaluation in a randomized controlled trial.

How long can patients with mild or moderate Alzheimer’s dementia maintain both the cognition and the therapy of cholinesterase inhibitors: a national population‐based study

The aims of this study were to evaluate the duration of acetylcholinesterase inhibitors (AChEI) utilization as well as the patients' cognition maintenance. This study was using panel data from the Bureau of National Health Insurance (BNHI) of Taiwan from 2001 to 2004. Patients with mild or moderate AD were prescribed AChEI (donepezil, rivastigmine, or galantamine). By the regulation of BNHI, if the score of Mini-Mental Status Examination worsened by more than two points or clinical dementia rating (CDR) worsened by one or more grades in the follow-up every half year, the AChEI treatment would be terminated. Kaplan-Meier product-limit method was used to estimate duration of drug utilization. Regression model was performed to analyse the factors affecting the discontinuation of AChEI treatment. Our results showed female are more and younger than male in mild to moderate Alzheimer's dementia. The mean duration of use of AChEI was 432 days. Only 9.6% of patients maintained stable cognition tests results with continued drug refill for more than 3 years. Discontinuation rate in older patients (age > or =76 years) was higher than those in younger age (P = 0.0009). The average duration for AChEI therapy is around 14 months. The elderly are at high risk for treatment discontinuation.

Acetylcholinesterase Inhibitors and Sleep Architecture in Patients with Alzheimer???s Disease

Studies suggest that some acetylcholinesterase inhibitors (AChEIs) increase rapid eye movement (REM) sleep and nightmares in patients with Alzheimer's disease (AD) but few have studied their effect on other sleep parameters. The objective of this study was to examine differences in sleep architecture in AD patients taking different AChEIs. 76 participants (51 men, 25 women) [mean age = 78.2 years; SD = 7.7] with mild to moderate AD underwent medication history screening as well as polysomnography to determine the percentage of each sleep stage. Participants were divided into groups based on AChEI used: donepezil (n = 41), galantamine (n = 15), rivastigmine (n = 8) or no AChEI (n = 12). General univariate linear model analyses were performed. AChEI therapy had a significant effect on the percentage of stage 1 (p = 0.01) and stage 2 (p = 0.03) sleep. Patients in the donepezil group had a significantly lower percentage of stage 1 sleep than patients in the galantamine group (mean = 17.3%, SD = 11.7 vs 29.2%, SD = 15.0, respectively; p = 0.01), but there was no significant difference between the donepezil group and the rivastigmine (mean = 25.0%, SD = 12.3) or no AChEI groups (mean = 27.6%, SD = 17.7) in this respect. No significant differences in percentage of stage 1 between other groups were seen. Patients in the donepezil group also had a significantly higher percentage of stage 2 sleep than patients in the no AChEI group (mean = 63.6%, SD = 14.4 vs 51.4%, SD = 16.9, respectively; p = 0.04), but there was no significant difference between the donepezil group and either the galantamine group (mean = 56.5%, SD = 8.7) or the rivastigmine group (mean = 59.9%, SD = 8.4). There were no significant differences between groups in terms of percentage REM sleep or other sleep parameters. Subgroups of AD patients (classified according to AChEI treatment) in this study differed with respect to the amount of stage 1 and stage 2 sleep experienced, with the donepezil-treated group having the lowest percentage of stage 1 sleep and the highest percentage of stage 2 sleep. There was no significant difference in the amount of REM sleep between the groups. Our data suggest that sleep architecture may be affected by the use of donepezil in patients with AD. Although not elicited in this study because of the small sample size, there may be a class effect of AChEIs on sleep architecture. Double-blind, placebo-controlled studies are needed to better understand causality and the effect of each AChEI on sleep architecture in patients with AD.

Acetylcholinesterase inhibitors for the treatment of dementia in Alzheimer’s disease: do we need new inhibitors?

Acetylcholinesterase inhibitors (AChEIs) have been shown to produce a small, but significant, improvement in cognition in patients with Alzheimer’s disease. However, not all patients respond equally, and cognitive benefit may be of limited duration. Although new AChEIs continue to be developed, more recent studies have been aimed at developing inhibitors that have additional actions separate from AChE inhibition. Importantly, new treatments that target the underlying pathogenic mechanism of Alzheimer’s disease (statins, secretase inhibitors, vaccination) may eventually emerge. These new treatments could make AChEI therapy less relevant for treatment of Alzheimer’s disease.

Clinical predictors of response to Acetyl Cholinesterase Inhibitors: experience from routine clinical use in Newcastle.

Acetyl Cholinesterase Inhibitors (AChEIs) have been in clinical use for the past five years in the UK for the symptomatic treatment of Alzheimer's disease (AD). There are few data on the patterns and predictors of response to AChEI therapy in routine clinical practice. We therefore investigated clinical variables that may distinguish between AChEI responders and non-responders. A retrospective sample of 160 consecutive patients with dementia who were treated on clinical grounds with an AChEI was studied. Treatment response was defined in two ways: (a) A clinical response was achieved when there was no deterioration or there was an improvement on a global clinical assessment (CGI) and (b) a Mini-Mental-State-Examination (MMSE) response when there was an improvement of 2 or more MMSE points. A total of 62 (45%) patients achieved an MMSE response. A diagnosis of dementia with Lewy Bodies (DLB) and Parkinson's disease+Dementia (PDD) was associated with a MMSE response, as were hallucinations, and lower MMSE scores at baseline. 125 (78%) patients achieved a CGI response for which there were no clinical predictors. Severity of illness, a diagnosis of DLB and PDD, and presence of hallucinations at baseline were predictive of a MMSE response. Non-AD dementia and severe dementia responded equally well to AChEI treatment and results of further randomised, placebo-controlled studies are needed to clarify the role of AChEI in the treatment of these disorders.