For whom and for what the definition of severe dementia is useful: an EDCON consensus.

The European Dementia Consensus Network (EDCON) is a special project of the Madariaga Foundation located in Brussels. The Madariaga Foundation seeks to facilitate collaboration between European countries and between the public and private sector. This paper will review the differences in the definitions of Severe Dementia and summarise the EDCON consensus on their implications for management. EDCON recommends that:--The attributes of the person suffering from dementia should be given as much attention (and are as important for care) as the severity of cognitive decline in dementia;--The dementia syndrome (particularly in it's severe form) is inadequately defined by criteria which only includes the domain of cognition;--Physical, legal, social and cultural factors defining the environment of patients and their families should be carefully examined and that the results of this examination should be used in conjunction with the results of the somatic and psychiatric assessment in planning care and placement of the patient;--patients with severe dementia should have access to palliative care; - family members should be included in the care plans for those with severe dementia who are in institutional care.

Metrifonate for Alzheimer's disease.

BACKGROUND: Metrifonate is a long-acting irreversible cholinesterase inhibitor, originally used to treat schistosomiasis. Its potential to enhance central nervous system cholinergic neurotransmission led to clinical trials for the treatment of people with Alzheimer's disease (AD). Although low incidence of serious side effects occurred during short-term use as an antihelmintic, in studies of the treatment of AD extending over 6 months, 20 patients experienced respiratory paralysis and problems with neuromuscular transmission. These findings have led to a halt to trials of metrifonate for AD and Bayer, the pharmaceutical company, has withdrawn its FDA application. OBJECTIVES: 1) To establish the efficacy of metrifonate for patients with Alzheimer's disease, in terms of cognition, global impression, functional activity, non cognitive symptoms, rate of institutionalization and mortality.2) Assess the safety and tolerability of metrifonate. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 5 December 2005 using the term metrifonat*. This Register is regularly updated with records from all major health care databases (MEDLINE, EMBASE, CINAHL, PsycINFO) and many trials databases. One of the authors (LS), as member of the Metrifonate Study Group has had the opportunity to contact other metrifonate trialists to obtain data from potentially non published data of metrifonate clinical trials. SELECTION CRITERIA: All unconfounded, randomized double-blind clinical controlled trials comparing metrifonate to placebo in people with AD. DATA COLLECTION AND ANALYSIS: Data were extracted by the two reviewers, cross-checked, and pooled when appropriate and possible. MAIN RESULTS: Most studies assessed changes in cognitive function, global function, activities of daily living, behavioural problems, severity of disease and adverse events. Occasionally the results were not reported in sufficient detail to allow extraction of data for the meta-analyses. The treatment regimens were varied: loading doses were used in some trials. The range of maintenance doses and studies were not pooled unless the treatment regimens were considered comparable. The lengths of treatment varied from 6 to 26 weeks and studies were not pooled unless the treatment duration was similar. The results are derived from the ITT populations. Metrifonate at various doses, fixed and loading doses, was associated with significant cognitive improvement compared to placebo, except for weekly doses where there was no difference from placebo: MMSE (metrifonate 60-80 mg/day with initial loading at 26 weeks; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD 1.85, 95% CI 1.06 to 2.64, p<0.00001); ADAS-Cog (metrifonate 60-80 mg/day with initial loading at 26 weeks MD -3.24, 95% CI -4.40 to -2.08, p<0.00001)In most trials, there was improvement in clinical global impression: CIBIC-Plus (metrifonate 30-55 mg/day, approximately 0.65 mg/kg body weight, with initial loading at 26 weeks MD -0.25, 95% CI -0.41 to -0.09 p=0.002; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD -0.20, 95% CI -0.39 to -0.01, p=0.04). There were generally-significant drug-placebo differences in activities of daily living but this often depended on sample size and the characteristics of the instrument used: DAD (metrifonate 30-55 mg/day, 0.65 mg/kg body weight, with initial loading at 26 weeks MD 2.72, 95% CI 0.66 to 4.77, p=0.01; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD 4.07, 95% CI 0.29 to 7.85, p=0.03)Also there were differences associated with metrifonate compared with placebo for different doses of metrifonate in scores on a behavioural symptom scale, caregiver burden scale, and severity of disease scale. Adverse events occurring more often with metrifonate included abdominal pain, bloating, bradycardia, diarrhoea, leg cramps, nausea and rhinitis and were described as mostly mild and transient, but occasionally moderately severe, and infrequently severe and serious. Analysis of the number of patients suffering at least one mild, moderate, severe or serious adverse event before the end of treatment showed that there was usually no difference between placebo and metrifonate. AUTHORS' CONCLUSIONS: Metrifonate given once per day appears to be related to clinical response in cognition, global improvement, and activities of daily living in patients with mild to moderate Alzheimer's disease. Tolerability is good with adverse events as expected from a cholinesterase inhibitor, but with a low incidence of neuromuscular dysfunction and respiratory failure, too low to be detected in this review. It has been withdrawn from further development.

Alivio del dolor como parte de los cuidados al final de la vida / Pain relief as part of end-of-life care

Los cuidados al final de la vida deben formar parte de un proceso asistencial que, partiendo de la Valoración Geriátrica Integral y de la elaboración de una detallada Lista de Problemas, permita compatibilizar el tratamiento adecuado y riguroso de las enfermedades crónicas y sus procesos intercurrentes con cuidados paliativos de calidad. Hasta el 25-50% de los mayores que viven en su domicilio y el 45-80% de los que viven en residencias presentan dolor persistente, y hasta el 80% de los pacientes con cáncer presentan dolor. Con tratamiento adecuado podemos lograr el alivio del dolor en el 75-90% de los pacientes, si bien este porcentaje no se obtiene en la práctica clínica habitual. Con herramientas teóricamente a nuestro alcance: atención sectorizada y coordinada, trabajo interdisciplinario y continuidad de cuidados, que incluyan medidas no farmacológicas y tratamiento farmacológico, podríamos hacer una utilización más eficiente de los recursos y al mismo tiempo conseguir nuestro objetivo: el alivio del dolor

End-of-life care must be part of a process, based on comprehensive geriatric assessment and a detailed checklist of clinical problems, that allows appropriate and rigorous treatment of chronic diseases and their intercurrent processes to be combined with high quality palliative care. Up to 25-50% of the community-dwelling elderly population and 45-80% of nursing home residents have persistent pain, and up to 80% of cancer patients suffer pain. Appropriate treatment can ameliorate pain in approximately 75-90% of patients, although this percentage is far from that achieved in routine clinical practice. Tools that are theoretically within our reach, such as sectorised and coordinated healthcare, interdisciplinary approaches and continuity of care, as well as pharmacological and non-pharmacological management, could lead to more efficient resource use and help us reach our main objective: pain relief

Alimentación y cáncer / Diet and cancer

El cáncer es la segunda causa de muerte en los países desarrollados. Su incidencia aumenta con la edad y la dieta es la causante en al menos un 30% de los casos. El riesgo es menor en poblaciones con un alto consumo de alimentos de origen vegetal. Es importante que reconozcamos que el cáncer, como otras enfermedades crónicas, se puede prevenir para reducir los años potenciales de vida perdidos y las tasas de incapacidad. Para conseguirlo disponemos de las guías alimentarias. Cuando la enfermedad se presenta podemos indicar modificaciones dietéticas para mejorar el estado nutricional del paciente, y en la fase terminal debemos respetar su opinión

Cancer is the second cause of death in the developed world. Its incidence increases with age and diet is responsible for at least 30% of cases. The risk is lower in populations with a high consumption of foods of vegetable origin. To reduce the number of potential years of life lost and disability rates, it is important that we recognise that cancer, like other chronic diseases, can be prevented. To achieve this, dietary recommendations are available. When the disease develops, dietary modifications to improve the patient's nutritional status can be indicated. In the terminal phase of the disease, the patient's opinion should be respected

Diarrea crónica y colitis microscópica: ¿una asociación frecuente en medicina geriátrica? / Chronic diarrhoea and microscopic colitis: a frequent association in geriatric medicine?

La diarrea es un problema clínico frecuente que puede ser expresión de enfermedades sistémicas, intestinales o bien estar en relación con formas de colitis de descripción relativamente reciente que pueden plantear dificultades de diagnóstico diferencial, por lo que se debe estar preparado para reconocerlas. En este sentido, la colitis microscópica es una causa no excesivamente infrecuente de diarrea crónica en el paciente geriátrico con colonoscopia normal y que requiere biopsias colónicas para llegar al diagnóstico. Esta entidad tiene dos subtipos, colitis colágena y linfocítica, según la presencia o ausencia de una banda colágena subepitelial engrosada, y que posiblemente correspondan a variantes de la misma enfermedad, con una clínica similar en ambas. Aunque un escaso porcentaje de pacientes presenta remisión espontánea, la evolución es por lo habitual intermitente y destaca que, a pesar del escaso número de ensayos terapéuticos controlados, dispone de un tratamiento eficaz para el control sintomático. (AU)

Hipotiroidismo e hipertiroidismo subclínicos en el anciano / Subclinical thyroid dysfunction in the elderly

La disfunción tiroidea, tanto clínica como subclínica, es frecuente en ancianos y el diagnóstico es difícil, ya que muchos de los síntomas pueden simular los efectos producidos por el envejecimiento u otras enfermedades. Por ello, en bastantes ocasiones se recurre al cribado sistemático. Los resultados de las pruebas de función tiroidea son con frecuencia anormales, pero su trascendencia clínica y la necesidad de tratamiento son muy variables. El hipotiroidismo y el hipertiroidismo manifiestos siempre precisan tratamiento, pero no está claro qué debe hacerse en casos de anomalías subclínicas de la función del tiroides (AU)

Nimodipine for primary degenerative, mixed and vascular dementia.

BACKGROUND: Dementia is an age-associated syndrome most commonly due to Alzheimer's disease (AD) and/or cerebrovascular disease. Calcium has an important role in regulating brain functions. Calcium ions link membrane excitation to subsequent intracellular molecular responses. Age-associated changes in calcium homoeostasis have possible repercussions on higher cortical functions. Nimodipine is an isopropyl calcium channel blocker which readily crosses the blood-brain barrier. Its primary action is to reduce the number of open calcium channels in cell membranes, thus restricting influx of calcium ions into cells. The usefulness of nimodipine in patients with Alzheimer's disease and vascular dementia and unspecified dementia is still controversial. In spite of the uncertainties about its efficacy in dementia, nimodipine is currently frequently prescribed for cognitive impairment and dementia in several continental European countries. OBJECTIVES: To assess the clinical efficacy of nimodipine for the manifestations of dementia, in unclassified disease and in the major subtypes - Alzheimer's disease, cerebrovascular disease, and mixed Alzheimer's and cerebrovascular disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register - which contains reports of trials from all major medical databases and many trial databases - was last searched on 3 August 2001 using the term 'nimodipin*'. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with nimodipine was administered for more than a day and compared with placebo in patients with dementia, of unclassified type or attributable to Alzheimer's disease, cerebrovascular disease, or mixed Alzheimer's and cerebrovascular disease. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and the odds ratio (95%CI) or the average difference (95%CI) were estimated. Both intention-to-treat and on-treatment results were extracted. MAIN RESULTS: Fourteen trials were included which tested two treatment regimes, 90 and 180 mg/day of nimodipine for 12 and 24 weeks. Two trials included only patients with Alzheimer's disease (AD), 9 trials included only patients with cerebrovascular dementia (CVD), and three trials included patients with AD, CVD and mixed disease. Available outcome data from 9 trials (2492 patients) cover the domains of cognitive function, activities of daily living, global clinical state, safety and tolerability. By pooling available data from all trials, whatever the diagnosis of the patients included, this review found benefit associated with nimodipine (90 mg/day at 12 weeks) compared with placebo on the SCAG scale ( WMD -7.59, 95% CI -9.87 to -5.31, P<0.00001) on clinical global impression (WMD -0.87, 95% CI -1.07 to -0.67, P<0.00001) and cognitive function (SMD 0.61, 95% CI 0.42 to 0.81, P<0.00001) but not on scales assessing activities of daily living. When the AD trials and the VD trials were pooled separately similar significant results were found for the 90mg/day dose of nimodipine at 12 weeks. Drop-out rates were low in the trials, affecting similar proportions of treatment and placebo groups. Nimodipine is well tolerated with a low rate of adverse effects similar to that associated with placebo. There were slightly more adverse cerebrovascular events, and adverse events due to blood problems, associated with placebo than with nimodipine, and adverse autonomic events were slightly more common with nimodipine than with placebo. REVIEWER'S CONCLUSIONS: Nimodipine can be of some benefit in the treatment of patients with features of dementia due to unclassified disease or to Alzheimer's disease, cerebrovascular disease, or mixed Alzheimer's and cerebrovascular disease. It appears to be well tolerated with few side effects. Data were not available from several trials, a total of more than 500 patients. A meta-analysis of individual patient data from all trials is desirable. Dementia is a chronic disorder and the short-term benefits of nimodipine demonstrated in the trials reviewed do not justify its use as a long-term anti-dementia drug. New research must focus on longer term outcomes.

Corticosteroids for acute ischaemic stroke.

BACKGROUND: Much of the brain swelling in ischaemic stroke is due to cytotoxic oedema, which is related to cell membrane dysfunction. Early treatment with corticosteroids may help reduce the swelling and improve the outcomes after a stroke. OBJECTIVES: The objective of this review was to assess the effect of corticosteroids in acute presumed ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched: 10 April 2001) and contacted investigators in the field. SELECTION CRITERIA: Published randomised trials comparing corticosteroids with placebo or control in people with acute (presumed or definite) ischaemic stroke. Trials were included if treatment began within 48 hours of stroke onset and if clinical outcome was assessed. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data. MAIN RESULTS: Seven trials involving 453 people were included. Details of trial quality that may relate to bias were not available from most trials. No difference was shown in the odds of death within one year (odds ratio 1.08, 95% confidence interval 0.68 to 1.72). Treatment did not appear to improve functional outcome in survivors. Six trials reported neurological impairment but pooling the data was impossible because no common scale or time interval was used. The results were inconsistent between individual trials. The only adverse effects reported were small numbers of gastrointestinal bleeds, infections and deterioration of hyperglycaemia across both groups. Results unchanged since last update. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate corticosteroid treatment for people with acute presumed ischaemic stroke. Conclusions unchanged since last update.

Thiamine for Alzheimer's disease.

BACKGROUND: Vitamin B1 (thiamine) plays an important role in Wernicke-Korsakoff syndrome (a form of amnesia caused by brain damage occurring in long-term alcoholics who rely mainly on alcohol for nutrition). The acute syndrome is normally reversible but may proceed to profound dementia, although its progress can be stopped by a timely injection of a large dose of thiamine. There have been suggestions that thiamine may have a beneficial effect in Alzheimer's disease. OBJECTIVES: The objective of this systematic review is to evaluate the efficacy of thiamine for people with Alzheimer's disease. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Issue 3:2000), the CDCIG Trials Register and other sources were searched for this update in July 2000 using the terms 'alzheimer*', thiamin* and vitamin B1'. In addition bibliographies of published reviews, and conference proceedings were searched and pharmaceutical companies and trials investigators were contacted. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with thiamine was administered for more than a day and compared with placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and the odds ratios (95% CI) or the average differences (95% CI) were estimated. MAIN RESULTS: There are three included studies, but few results were reported that could be included. The cross-over studies did not report results from the first phase. It was not possible to pool any results for a meta-analysis. Nolan 1991 reports results that show no evidence of an effect on MMSE at 3, 6, 9 and 12 months for thiamine compared with placebo for those who completed the trial. Meador 1993a noted that 3/8 on thiamine compared with 6/9 on placebo were worse as measured on the ADAS-Cog at 3 months compared with baseline, but the difference is not statistically significant. Blass 1988 and Nolan 1991 reported that no significant side-effects were noted during the study, and Meador 1993a did not mention side-effects. Blass 1988 noted that 5/16 and Nolan 1991 that 5/15 did not complete the study, but neither mentioned the groups to which these people belonged. REVIEWER'S CONCLUSIONS: It is not possible to draw any conclusions from this review. The number of people included in the studies if less than 50 and the reported results are inadequate.

Efficacy and safety of nicotine on Alzheimer's disease patients.

BACKGROUND: Nicotine is a cholinergic agonist that also has a presynaptic effect in releasing acetylcholine. In animal model has been shown to reverse spatial memory deficits produced by lesions in the medial septal nucleus of rats, and in aged monkeys nicotine administration improves memory and alertness to visual stimuli. Observational studies have claimed a protective effect of smoking against Alzheimer's disease (AD), but recent studies have called this into question. Smoking is a risk factor for stroke and so, possibly, for vascular dementia. Because nicotine has adverse effects, it is important to conduct a systematic review to assess the clinical efficacy and safety of nicotine for patients with AD OBJECTIVES: To evaluate the efficacy and safety of nicotine, administered in any way or form, for people with Alzheimer's disease. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 24 January 2001 using the term nicotine. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with nicotine patches or administration of nicotine intravenously or in any other way or form was administered for more than a day and compared with placebo for people with Alzheimer's disease. DATA COLLECTION AND ANALYSIS: The one included trial did not present results suitable for inclusion in the review. MAIN RESULTS: The poor quality of trials did not allow any synthesis of data across studies. REVIEWER'S CONCLUSIONS: This review is not able to provide any evidence that nicotine is a useful treatment for Alzheimer's disease.

Corticosteroids for acute ischaemic stroke.

BACKGROUND: Much of the brain swelling in ischaemic stroke is due to cytotoxic oedema, which is related to cell membrane dysfunction. Early treatment with corticosteroids may help reduce the swelling and improve the outcomes after a stroke. OBJECTIVES: The objective of this review was to assess the effect of corticosteroids in acute presumed ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register and contacted investigators in the field. SELECTION CRITERIA: Published randomised trials comparing corticosteroids with placebo or control in people with acute (presumed or definite) ischaemic stroke. Trials were included if treatment began within 48 hours of stroke onset and if clinical outcome was assessed. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data. MAIN RESULTS: Seven trials involving 453 people were included. Details of trial quality that may relate to bias were not available from most trials. No difference was shown in the odds of death within one year (odds ratio 1.08, 95% confidence interval 0.68 to 1.72). Treatment did not appear to improve functional outcome in survivors. Six trials reported neurological impairment but pooling the data was impossible because no common scale or time interval was used. The results were inconsistent between individual trials. The only adverse effects reported were small numbers of gastrointestinal bleeds, infections and deterioration of hyperglycaemia across both groups. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate corticosteroid treatment for people with acute presumed ischaemic stroke.

Nimodipine for primary degenerative, mixed and vascular dementia.

BACKGROUND: Dementia is an age-related condition in which Alzheimer's disease (AD) and cerebrovascular disease account for the bulk of cases. The role played by calcium in regulating brain functions is well known - the calcium ion links membrane excitation to subsequent intracellular enzymatic response. Change in calcium homeostasis is one important effect of aging with repercussions on higher cortical functions. Nimodipine is an isopropyl calcium channel blocker which can easily cross the blood brain barrier. Its primary action is to reduce the number of open channels, thus restricting influx of calcium ions into the cell. The usefulness of nimodipine in patients with Alzheimer's disease and vascular dementia and unspecified dementia is still controversial with mixed results. In spite of the uncertainties about its efficacy in dementia, nimodipine is currently a frequently prescribed drug for cognitive impairment and dementia in several European countries. This review will be conducted in two phases; the current review is based on evidence from published data only. The second phase will be based on individual-patient data analysed centrally and added to this review in due course. OBJECTIVES: To determine the clinical efficacy of nimodipine for the symptoms of dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'nimodipine' and 'isopropyl (2-methoxy-ethyl) 1,4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate'. SELECTION CRITERIA: All unconfounded, double-blind, randomised trials in which treatment with nimodipine was administered for more than a day and compared to placebo in patients with dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and the odds ratio (95%CI) or the average difference (95%CI) were estimated. Both intention-to-treat and on-treatment results were extracted. MAIN RESULTS: This review produced no clear results. Many of the data published were not capable of being sensibly pooled. The data were compatible with nimodipine producing improvement, no change or even harm for those with Alzheimer's disease, vascular dementia, or mixed Alzheimer's and vascular dementia. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analysis, based on one study only, failed to detect any difference between nimodipine and placebo (OR 0.53; 95%CI 0.25 - 1.13). An on-treatment analysis, based on one study only, produced a statistically significant difference in favour of nimodipine (SMD 4.4; 95%CI 3.9 - 5.0). For cognitive function, the effect of nimodipine was statistically significantly different from placebo for the Mini Mental State Examination score (0-30; high =good) (SMD 0.9; 95%CI 0.59 - 1.22) and there was a statistically significant effect in favour of treatment for the Wechsler Memory Scale (SMD 0.47; 95%CI 0.17 - 0.77). These analyses were based only on those who completed the study and not intention-to-treat analyses. There were no results presented in a form suitable for pooling for functional autonomy, behaviour, quality of life dependency (eg institutionalization), effect on carer, death, acceptability of treatment (as measured by withdrawal rate, safety (as measured by the incidence of adverse effects, including side effects, leading to withdrawal). REVIEWER'S CONCLUSIONS: This review provides no convincing evidence that nimodipine is a useful treatment for the symptoms of dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. (ABSTRACT TRUNCATED)

Thiamine for Alzheimer's disease.

BACKGROUND: Vitamin B1 (thiamine) plays an important role in Wernicke-Korsakoff syndrome (a form of amnesia caused by brain damage occurring in long-term alcoholics who rely mainly on alcohol for nutrition). The acute syndrome is normally reversible but may proceed to profound dementia, although its progress can be stopped by a timely injection of a large dose of thiamine. There have been suggestions that thiamine may have a beneficial effect in Alzheimer's disease. OBJECTIVES: The objective of this systematic review is to evaluate evidence of the effect of thiamine for Alzheimer's disease. SEARCH STRATEGY: The Cochrane Controlled Trials Register and the CDCIG Register were searched using the terms 'thiamine*, alzheimer* and vitamin* B1'. Other sources were also searched. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with thiamine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95% CI) or the average differences (95% CI) were estimated. No intention-to-treat data were available to be used. MAIN RESULTS: Few data were available for review. The data were compatible with thiamine producing harm, no change or improvement. For measures of cognition, the effect of thiamine was non-significantly worse than placebo on the Mini Mental State Examination score (0-30; high=good) at 12 months: WMD -4.3 (95% CI: -14.4 - +5.8) and at time points 3, 6 and 9 months. Change from baseline analyses showed placebo to be significantly better than thiamine at all time points beyond three months; WMD -4.8 (95% CI: -6.0 to -3.6) at 12 months. There was no statistically significant difference in the test of Verbal Fluency and the Boston Naming Test. These analyses were based only on those who completed the study and not on intention-to-treat analyses. There were no results presented for withdrawal by treatment group. Data on measures of functional autonomy, behaviour, quality of life, dependency, or effect on carer were not available. REVIEWER'S CONCLUSIONS: This review finds no evidence that thiamine is a useful treatment for the symptoms of Alzheimer's disease. The data are so poor and sparse that it is difficult to state almost anything of its effect in Alzheimer's disease. Thiamine cannot be recommended for patients with Alzheimer's disease.

Nicotine for Alzheimer's disease.

BACKGROUND: Nicotine is a cholinergic agonist that acts, not only post-synaptically, but also releases pre-synaptic acetylcholine, and in animal models has been shown to reverse spatial memory decline in rats with lesion in the medial septal nucleus and to show recovery on memory in aged monkeys. Nicotine also has effects on other transmitters like serotonin (5HT), dopamine, or GABA. On the other hand, because nicotine has serious adverse effects, especially concerning cardiovascular risks in elderly people, and also on sleep and behavior, there are several important reasons to conduct a systematic review to assess the clinical efficacy and safety of nicotine in patients with AD. OBJECTIVES: The aim of this review is to determine whether there is evidence of beneficial effect, and to assess its safety profile, when nicotine is used for Alzheimer's disease. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Issue 2, 99) was searched using the terms nicotin* and alzheimer*. Three references to trials were deemed suitable for inclusion but are awaiting consideration while the investigators are contacted. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with nicotine patches or administration of nicotine intravenously was administered for more than a day and compared to placebo in people with Alzheimer's disease. DATA COLLECTION AND ANALYSIS: As no trials were suitable for inclusion, no data have been extracted or pooled in a meta-analysis. One trial is awaiting consideration, and if included in an update of this review, any available data will be incorporated. MAIN RESULTS: The poor quality of the trials did not allow any synthesis of results across studies. However, the data available in trials considered are compatible with nicotine producing harm, no change or improvement. REVIEWER'S CONCLUSIONS: This review is not able to provide reliable evidence that nicotine is a useful treatment for Alzheimer's disease.