INTRODUCTION. The rates of cognitive decline in patients with Alzheimer's disease show variations due to various factors. AIM. To determine the influence of age, education, gender, activities of daily living (ADL) and acetylcholinesterase inhibitors (IAChE) and memantine in the rhythm and rate of cognitive decline. PATIENTS AND METHODS. Retrospective study of a sample of 383 patients with Alzheimer's disease, with neuropsychological assessments over three years. Cognitive measure was used as the Cambridge Cognitive Examination (CAMCOG). Patients were grouped according to their rate of annual decline (RAD) and performed a bivariate and multivariate regression analysis using as dependent variable the difference in scores on the CAMCOG (baseline-final). RESULTS. The younger age (beta = -0.23; p < 0.001), more educated (beta = 0.26; p < 0.001) and the greater deterioration of ADL (beta = 0.24; p < 0.001) were associated with a greater decline in all patients. The drugs had a beneficial effect (beta = -0.18; p = 0.011) in the group with lower and slower decline (RAD < 5%). CONCLUSIONS. The lower age, higher education and the deterioration of ADL are associated with a greater cognitive decline. The IAChE and memantine had a beneficial effect, slowing the decline in the group of patients with lower RAD.
Title: Characteristics of patients with Alzheimer's disease who switch to rivastigmine transdermal patches in routine clinical practice Lopez-Pousa S, Arranz FJ Ref: Patient Prefer Adherence, 7:47, 2013 : PubMed
BACKGROUND: The aim of this study was to assess the sociodemographic and clinical characteristics of patients with Alzheimer's disease who switched from any oral cholinesterase inhibitor to rivastigmine patches. METHODS: An observational, retrospective, multicenter study was conducted in patients with a diagnosis of Alzheimer's disease who had switched to rivastigmine patches within the previous year in the routine clinical practice of 150 neurologists. Sociodemographic, clinical, and therapeutic data were collected in one office visit. Stepwise logistic regression models were used to find associations. RESULTS: Data were obtained from a total of 1022 patients and their caregivers, and showed a mean age of 78.4 +/- 6.62 years, 62.61% being women, and mostly having a family caregiver. The switch to rivastigmine patches was mainly instigated on the initiative of the physician (82.39%) or on request of the caregiver (21.23%) or patient (10.37%). Reasons for the switch included improving ease of administration (56.65%), tolerability (36.79%), efficacy (31.60%), and adherence (18.59%). Prior treatment with oral rivastigmine versus donepezil or galantamine increased the probability of switching in order to improve ease of administration (odds ratio, oral rivastigmine versus donepezil 4.20, P < 0.0001; odds ratio, oral rivastigmine versus galantamine 3.55, P < 0.0001). Conversely, previous treatment with donepezil or galantamine produced an approximate four-fold increase in the odds of switching due to lack of efficacy. A higher level of education as well as more concomitant diseases increased the probability of switching because of intolerance. CONCLUSION: Improved ease of administration was the main reason for switching to transdermal rivastigmine. Other reasons involved in the decision to switch to rivastigmine patches included sociodemographic and clinical characteristics, including the educational level of patients and caregivers, number of concomitant diseases, and previous treatment for Alzheimer's disease.
INTRODUCTION: Clinical evidence indicates that acetylcholinesterase inhibitors (AChEIs) are not efficacious to treat frontotemporal lobar degeneration (FTLD). The British Association for Psychopharmacology recommends avoiding the use of AChEI and memantine in patients with FTLD. METHODS: Cross-sectional design using 1092 cases with Alzheimer's disease (AD) and 64 cases with FTLD registered by the Registry of Dementias of Girona. Bivariate analyses were performed, and binary logistic regressions were used to detect variables associated with antidementia drugs consumption. RESULTS: The AChEIs were consumed by 57.6% and 42.2% of the patients with AD and FTLD, respectively. Memantine was used by 17.2% and 10.9% of patients with AD and FTLD, respectively. Binary logistic regressions yielded no associations with antidementia drugs consumption. CONCLUSIONS: There is a discrepancy regarding clinical practice and the recommendations based upon clinical evidence. The increased central nervous system drug use detected in FTLD requires multicentric studies aiming at finding the best means to treat these patients.
BACKGROUND: Limited information exists regarding the consumption of psychopharmaceuticals for non-Alzheimer's degenerative dementias (n-ADDs), despite the fact that the treatment of neuropsychiatric symptoms of these diseases is an important challenge for clinicians. OBJECTIVE: The aim of this study was to describe sociodemographic and clinical data from 235 patients with various subtypes of n-ADD, together with the level of consumption of pharmaceuticals with central nervous system activity. METHODS: A descriptive, observational, cross-sectional study was conducted using the data registered by the Registry of Dementias of Girona, northeast Catalunya, Spain. All drugs were categorized according to the Anatomical Therapeutic Chemical Classification System. RESULTS: The results showed a high level of psychopharmaceutical prescription: 48.9 % of the n-ADD patients used acetylcholinesterase inhibitors and 9.8 % used memantine. Antipsychotics and benzodiazepines were prescribed to 45.5 and 46.8 % of the patients, respectively. Antidepressants were consumed by 70.2 % of the registered cases. CONCLUSIONS: High levels of psychopharmaceutical prescribing were observed in our study and many of these prescriptions lacked specific indications for n-ADDs. It is necessary to consider the risk-benefit relationship before prescribing pharmaceuticals. Specific training programmes will be necessary to improve the use of pharmaceuticals in n-ADD patients.
INTRODUCTION: Metabolic syndrome (MS) results in an increased risk of developing Alzheimer's disease (AD), but its implications when the disease is already well established remain unknown. AIM. To assess the influence of MS in the clinical manifestations and its effect on mortality among AD patients treated with anti-Alzheimer drugs. PATIENTS AND METHODS: We conducted a retrospective cohort study with 751 outpatients from a dementia clinic who were diagnosed with AD and who had been prescribed cholinesterase inhibitors and/or memantine. Data was collected in a standardised manner from the patients' medical records. RESULTS: The mean follow-up time was 27.52 +/- 12.15 months. Frequency of MS was 24.6% (n = 185). The mortality rate throughout the period of study was 14.0% (n = 105). Patients with MS are younger and present lower degrees of cognitive and functional impairment, with greater organic comorbidity at the expense of heart diseases. They take more medicines and are given fewer atypical antipsychotics at the expense of olanzapine, above all. When age, sex, the basic activities of daily living and conduct disorders subscales from the Blessed scale (BDRS), the Cumulative Illness Rating Scale (CIRS) for heart disease and the Folstein Mini-Mental State Examination (MMSE) were included in the model, MS did not increase the risk of mortality. CONCLUSIONS: Patients with MS are diagnosed with AD at an earlier age despite having a lower degree of cognitive and functional impairment. MS does not give rise to an increase in the mortality rate of patients with AD.
AIM: To evaluate the influence of metabolic syndrome (MS) and a history of heart disease on increased mortality rates among patients with Alzheimer's disease (AD) who have been treated with cholinesterase inhibitors or memantine and who received risperidone or olanzapine therapy during the time under study. PATIENTS AND METHODS: Our study involved a sample of 751 patients diagnosed with AD and treated with anti-dementia drugs. Of the total number, 10.2% (n = 77) and 7.7% (n = 58) had been treated with risperidone and olanzapine, respectively, at some time during the follow-up. Twelve (1.6%) had received both substances in different periods of time. RESULTS: Mean follow-up time was 27.52 +/- 12.15 months. Mortality rate stood at 14% (n = 105). The mean maximum dose of olanzapine was 4.3 mg/day (standard deviation, SD = 2.55; range = 2.5-15) and 1.36 mg/day (SD = 0.67; range = 0.25-3.5) in the case of risperidone. Treatment lasted 519.12 (SD = 285.2; range = 90-1045) and 481.68 (SD = 345.22; range = 1-1650) days, respectively. If age, sex, conduct disorders on the Blessed scale, the cumulative heart disease index and the global deterioration scale are included in the model, both olanzapine (relative risk, RR = 8.95; confidence interval, CI 95% = 2.856-28.046) and risperidone (RR = 4.526; CI 95% = 1.816-11.281) increase the risk of death. An interaction between a history of heart disease and risperidone is recorded, which suggests a possible protection of the drug in this group. No evidence was found of an interaction between the two drugs and MS. CONCLUSIONS: Neither the presence of cardiac disorders nor MS allow us to explain the increased mortality rate in patients with dementia who are treated with olanzapine or risperidone.
BACKGROUND AND OBJECTIVE:
To study the effect of clinical and demographic variables on mortality in patients with probable Alzheimer's disease treated with the cholinesterase inhibitor galantamine.
PATIENTS AND METHOD:
This retrospective cohort study reviewed 172 medical records, gathering information such as demographic and clinical variables, adverse events, number of withdrawals and duration of treatment with galantamine.
RESULTS:
Of 172 patients, 18.6% had adverse events. Galantamine was well tolerated in 15.4% of patients but they abandoned the treatment because of several reasons after a median duration of treatment of 13.3 months and an average dose of 15.0 mg/day. The overall rate of mortality was 12.5%, being, 19.0% for those who abandoned the treatment and 11.3% for those who dit not. The univariate analysis showed that patients who died were older, had had more antipsychotic medications, had a higher total Blessed score and had suffered from more episodes of heart failure. The associated variables in the multivariate analysis using a binary logistic regression were mortality, sex, age, hypertension, heart failure, arrhythmia, antipsychotic treatment and greater cognitive impairment.
CONCLUSIONS:
The duration and the dose of treatment with galantamine were not associated with increased mortality. Related variables were an advanced age, male sex, cardiovascular diseases and antipsychotic treatment.
BACKGROUND: few studies have analysed the effect of the long-term use of cholinesterase inhibitors (ChEIs) on mortality. OBJECTIVE: to compare the long-term effects of galantamine and donepezil treatment on the mortality rate in Alzheimer's disease (AD) patients. DESIGN: a retrospective cohort study. SETTING AND SUBJECTS: 404 patients referred by primary care centres to a Memory Clinic who were diagnosed with probable AD and who were prescribed treatment with donepezil or galantamine. METHODS: standardised review of the patient's medical records. RESULTS: 14.5% of the patients showed intolerance to the treatment with ChEIs during the first 15 days. Of those patients who initially tolerated the treatment, 18.5% gave it up after a mean duration of 13.36 months and a mean dose of 7.5 mg/day of donepezil or 14.3 mg/day of galantamine. The mean duration of the treatment in patients who did not abandon the treatment was 25.4 months and the mean dose was 8.1 mg/day of donepezil or 20.0 mg/day of galantamine. There were no differences in the mortality rate between patients treated with donepezil or galantamine (13.7 versus 12.2; P = 0.75). The multivariate analysis through binary logistic regression showed that the variables associated with mortality were male gender, older age, heart failure, treatment with antipsychotic drugs and a high score on the Global Deterioration Scale. CONCLUSIONS: the duration and the dose of donepezil or galantamine are not related to an increase in mortality. The related variables were advanced age, the severity of the dementia, being male, heart failure and treatment with antipsychotic drugs.
There are various anticholinesterase inhibitors (AChEIs) for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). All AChEIs have shown greater efficacy than placebo in randomized, double-blind, parallel-group clinical trials. No differential studies have yet been made of the efficacy between all AChEIs. The study aims to determine the differential efficacy of the AChEIs with respect to a historical sample of patients with AD that were not treated with AChEIs. An open-label, prospective, observational study with a retrospective control group was undertaken to examine the evolution of the cognitive function over a 6-month period. The patients were assessed with the Mini-Mental State Examination (MMSE) at study entry and at 6 months. A general linear model was applied for repeated measurements with the MMSE score as the dependent variable, treatment type as an independent variable and the severity of the deterioration, age and the MMSE baseline score as covariables. Of the sample of 147 patients, 40 initiated treatment with donepezil, 32 with galantamine, 30 with rivastigmine and 45 were part of a historical sample of the memory clinic patients between 1991 and 1996 that had not been treated with AChEIs. The average age was 73.7 years (SD = 6.9; range = 52-86), 67.3% were women, 78.2% of the cases were mild and the MMSE baseline score was 18.1 points (range = 11-27). No significant intergroup differences were observed in these variables. The average doses of donepezil, galantamine and rivastigmine were 5.87 mg/day (SD = 1.92), 14.81 mg/day (SD = 6.25) and 6.41 mg/day (SD = 1.82), respectively. At 6 months, the difference in the MMSE score with respect to the untreated group was 1.6 points for donepezil (95% CI 0.79-2.37; p < 0.001), 0.99 points for galantamine (95% CI 0.14-1.85; p = 0.01) and 0.90 points for rivastigmine (95% CI 0.05-1.74; p = 0.03). No significant differences were observed in the efficacy among the groups treated with AChEIs (p > 0.05). Treatment with AChEIs significantly delays the global cognitive impairment associated with AD for at least 6 months. Our study found no significant differences in efficacy between donepezil, galantamine and rivastigmine. Further studies in the context of daily clinical practice will determine the clinical significance of the changes observed. An important variability of the response to the treatment was observed in treated patients.
AIM The cognitive deficiency of Alzheimer's disease is attributed to a dysfunction in the cerebral cholinergic systems. Current drug treatments are directed at stimulating cholinergic transmission. The aim of this study was to evaluate the latest cholinergic drugs available an those about to appear in the market.
METHODS:
A review of the most recent studies published regarding the physiopathology of Alzheimer disease and the results following treatment with donepezil, rivastigmine and metriphonate was carried out.
RESULTS:
Donepezil is a specific, reversible acetylcholinesterase inhibitor of close to 100% absorption and a half-life of 70 h, achieving stable concentrations at approximately 3 weeks. Patients treated with a single daily dosis of 5 or 10 mg improve in the ADAS-Cog scale. The medication is initiated with a dosis of 5 mg/day. Rivastigmine is a competitive, pseudoirreversible inhibitor with a half-life of 2 h, although it acts for approximately 10 h. The Adas-Cog scale and the CIBIC-Plus improve in patients treated with a daily dosis of 6 or 12 mg taken in two doses. Administration should be initiated at low doses (3 mg/day) which are progressively increased. Metriphonate is a prodrug of short life which inhibits acetylcholinesterase through a metabolite (DDVP) with a half-life in the circulation of 2 h. Improvement is observed in the ADAS-Cog scale and the CIBIC-Plus and in behavior disorders at doses of 0.3 and 0.65 mg/kg/day. Doses between 30 and 60 mg/day are effective.
CONCLUSIONS:
Different studies carried out with the acetylcholinesterase inhibitors donepezil, rivastigmine and metriphonate have been effective in the control of the cognitive symptoms of Alzheimer disease in the initial or moderate phases of the disease.
OBJECTIVES To review the classical treatment for non cognitive symptoms in Alzheimer's disease and to estimate the possible future contributions.
DEVELOPMENT:
The non cognitive symptoms, with a high frequency in dementia, mean a larger clinical severity, an increment of institutionalization and a larger carer's emotional burden. Several treatment frequently used has been reviewed (antipsychotic, antidepressant, antianxiety, anticonvulsive...) and the response for some of this symptoms is relatively narrow and side effects are frequent and intense. New drugs, as cholinesterase inhibitors and cholinergic agonist, that have demonstrated their efficacy for the cognitive symptoms, seem to be also effective for non cognitive ones.
CONCLUSION:
The relative low effectivity of classical treatment and the frequency and intensity of side effects open new possibilities to cholinesterase inhibitors in the treatment of non cognitive symptoms in Alzheimer's disease.
To review the drugs commercially available at present and in the near future in relation to the evolution of Alzheimer disease, bearing in mind the possible psychiatric disorders which may be associated with the disease.
DEVELOPMENT:
The therapeutic approach is planned according to the different phases of the disease. In the preclinical phase, anti-inflammatory drugs and estrogens in post-menopausal women have been effective. In the initial phase current recognition therapy is directed basically towards correcting the break-down of acetylcholine (tacrine, donepezil, SB202026, SDZ ENA 713). For depressive symptoms serotonin levels are corrected using selective inhibitors of serotonin uptake.
CONCLUSIONS:
Drug treatment should be considered with the association of drugs which activate the malfunctioning circuits and/or pathways. It would also be useful to design clinical studies using pharmacological combinations of cholinergic agonists, estrogens, anti-inflammatory drugs, seligiline and/or new anti-cholinesterase drugs amongst others.
