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Psychosis is common among individuals with neurocognitive disorders, is difficult to manage, and causes considerable burden and stress to patients and caregivers. Developing effective treatments is a substantial unmet medical need but research has been slowed by the need for updated consensus diagnostic criteria. To address this need, the International Psychogeriatrics Association initiated a process to develop criteria for clinical use, research, and treatment development efforts. The process included clinical, regulatory, and industry stakeholders as well as input from a global network of experts in geriatric psychiatry responding to two surveys (N = 336). Results from the consensus process confirmed that clinicians wanted elaboration of aspects of the definition proposed by Jeste and Finkel in 2000 to ensure that the criteria are applied appropriately. Based on discussions, the survey, and emerging research, criteria were revised to apply to psychosis occurring with all major and mild neurocognitive disorders. Other important changes include providing examples of hallucinations and delusions and clarifying time course, impact, and exclusionary criteria. This definition of psychosis in major and mild neurocognitive disorders can be used to advance many types of research including development of much needed pharmacologic and nonpharmacologic interventions for psychosis in patients with neurocognitive disorders.

Introduction: Alzheimer's disease is the most common form of dementia worldwide. Aducanumab, a monoclonal antibody targeting amyloid-beta, became the first disease-modifying treatment for mild cognitive impairment due to Alzheimer's disease (AD) and mild AD dementia and suggested that removing amyloid from the brain, especially in early AD, might make a difference in slowing cognitive decline. Areas covered: In this review, the authors outline aducanumab's clinical efficacy as shown through key clinical trials and discuss its approval by the Food and Drug Administration under the accelerated pathway, which sparked both hope and controversy. We also discuss the importance of amyloid-related imaging abnormalities as a major side effect of aducanumab and all subsequent monoclonal antibodies targeting amyloid-beta. Expert opinion: Aducanumab, became the first monoclonal antibody that provided at least partial support for the amyloid hypothesis by demonstrating slowed cognitive decline by removing amyloid from the brain, although full FDA approval now seems unlikely due to discontinuation of its development. Its introduction raised awareness of ARIA, highlighted the significant costs and need for informed consent in treatment, and emphasized the importance of long-term, diverse, and combination therapy data for future AD treatments targeting amyloid and tau. [ABSTRACT FROM AUTHOR]

In July 2023, the U.S. Food and Drug Administration (FDA) granted full approval to lecanemab for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD dementia. Considering the limited treatment options for AD, the approval of lecanemab offers hope and opens the door for other disease-modifying therapies in the pipeline. In this review, the authors summarize the FDA treatment guidelines, other anti-amyloid agents, and drug information relevant to prescribers, such as pharmacology and pharmacokinetics. Relevant clinical trial outcomes are discussed along with their significance and controversies. While questions remain about the magnitude of lecanemab's clinical impact, its approval signifies major progress in addressing the underlying pathology of AD. The authors have confidence in lecanemab as a promising treatment option and foresee exciting advancements on the 5-year horizon. Yet, further research is needed regarding trials beyond 18 months, post-marketing surveillance, and lecanameb in combination with existing treatments and lifestyle interventions. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are commonly used for gastroesophageal reflux disease. Previous studies have raised concerns about the impact of PPIs on cognition in older adults, but the evidence supporting this concern is lacking. This article aims to analyse the available data regarding the impact of long-term PPI use on cognition in older adults. We searched PubMed for relevant studies conducted between 2015 and 2022. Seventeen such studies were identified. Limitations to available research data include the fact that studies are mainly observational, use heterogeneous study methods and do not account for confounding variables such as B12 deficiency, Helicobacter pylori infection, and thyroid dysfunction. Overall, this search did not find a compelling association between PPI use and cognitive decline. [ABSTRACT FROM AUTHOR]

The drug memantine may benefit Alzheimer patients who are also taking donepezil, according to a study of 404 patients. Patients who took memantine had higher scores on tests of cognition and ability to perform activities of daily living compared to those who took a placebo, or inactive substance. Memantine is an NMDA receptor antagonist.

An estimated 47 million people live with Alzheimer's disease (AD) and other forms of dementia worldwide. Although no disease-modifying treatments are currently available for AD, earlier diagnosis and proper management of the disease could have considerable impact on patient and caregiver quality of life and functioning. Drugs currently approved for AD treat the cognitive, behavioral, and functional symptoms of the disease and consist of three cholinesterase inhibitors (ChEIs) and the N-methyl-D-aspartate receptor antagonist memantine. Treatment of patients with mild to moderate AD is generally initiated with a ChEI. Patients who show progression of symptoms while on ChEI monotherapy may be switched to another ChEI and/or memantine can be added to the treatment regimen. In recent years, putative disease-modifying therapies have emerged that aim to slow the progression of AD instead of only addressing its symptoms. However, many therapies have failed in clinical trials in patients with established AD, suggesting that, once developed, disease-modifying agents may need to be deployed earlier in the course of illness. The goal of this narrative literature review is to discuss present treatment algorithms and potential future therapies in AD. [ABSTRACT FROM AUTHOR]

The relationship between antidepressants and Alzheimer's disease (AD) is very complex, and the literature is mixed regarding the effect of these medications on the trajectory of the disease. This paper reviews findings from relevant clinical studies that have assessed the impact of antidepressants on AD onset and disease progression. To date, these medications seem to attenuate the risk of developing the disease without affecting the rate of progression. However, most evidence stems from observational studies that are subject to methodological bias. Serotonergic antidepressants are thought to affect AD pathophysiology by reducing β-amyloid (Aβ) plaque formation and promoting hippocampal neurogenesis. However, the mechanisms underlying their effect need to be examined further, especially in humans. Moreover, more robust clinical studies in terms of design (randomized controlled trials) and longer duration of follow-up are needed. Variables, including depression timeline/onset and its clinical course, apolipoprotein E4 (APOE4) genotype status, sex, dose/duration of antidepressant treatment, and AD biomarkers need to be incorporated in future trials to better elucidate the effect of antidepressants on AD risk. [ABSTRACT FROM AUTHOR]

Cholinergic synapses are ubiquitous in the human central nervous system. Their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions. Several lines of research suggest additional roles for cholinergic systems in overall brain homeostasis and plasticity. As such, the brain's cholinergic system occupies a central role in ongoing research related to normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. The cholinergic hypothesis of Alzheimer's disease centres on the progressive loss of limbic and neocortical cholinergic innervation. Neurofibrillary degeneration in the basal forebrain is believed to be the primary cause for the dysfunction and death of forebrain cholinergic neurons, giving rise to a widespread presynaptic cholinergic denervation. Cholinesterase inhibitors increase the availability of acetylcholine at synapses in the brain and are one of the few drug therapies that have been proven clinically useful in the treatment of Alzheimer's disease dementia, thus validating the cholinergic system as an important therapeutic target in the disease. This review includes an overview of the role of the cholinergic system in cognition and an updated understanding of how cholinergic deficits in Alzheimer's disease interact with other aspects of disease pathophysiology, including plaques composed of amyloid-β proteins. This review also documents the benefits of cholinergic therapies at various stages of Alzheimer's disease and during long-term follow-up as visualized in novel imaging studies. The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression. [ABSTRACT FROM AUTHOR]

Background/Rationale: This report describes a quality improvement continuing medical education activity designed to enhance the recognition and treatment of residents with Alzheimer’s disease (AD) or other dementias in skilled-nursing facilities (SNFs). Methods: Charts were compared in 6 areas prior to and following (stages A and C) a live, faculty-led workshop (stage B). Four SNFs completed stages A (n = 67 residents) and B, and 3 SNFs completed stage C (n = 52 residents). All charts came from residents with AD or a diagnosis of dementia or dementia-like symptoms. Results/Conclusion: The SNFs had >95% baseline performance in both the frequency of cognitive assessments and documented medication reviews. The percentage of residents who received a quality-of-life assessment and those who had a mental health care plan in place represent areas for improvement. As part of this activity, a toolkit was developed to help guide facilities and clinicians in instituting care improvements for residents with AD/dementia. [ABSTRACT FROM AUTHOR]

Subjective cognitive impairment (SCI) refers to concerns regarding one's cognitive functioning in the absence of objective evidence of impairment, and may represent an early stage of Alzheimer's disease. However, as not all individuals with SCI cognitively decline, there is growing interest in the early identification of those individuals with SCI who are most at risk of developing Alzheimer's disease. One promising method of early identification involves the use of biomarkers that are known to be associated with the pathophysiology of the disease; in particular, markers of amyloid and tau accumulation. While there has been substantial research on amyloid and tau biomarkers in the context of mild cognitive impairment (MCI), only recently has attention shifted to SCI, which may represent an even earlier stage in the disease course. The purpose of this paper is to qualitatively review the literature on amyloid and tau biomarkers in SCI. A brief discussion of non-amyloid/tau biomarkers is also included. Not surprisingly, we found that amyloid and tau biomarker profiles become increasingly abnormal from SCI, to MCI, to Alzheimer's disease. Additionally, although amyloid and tau biomarkers appear to be unable to differentiate between SCI and healthy controls, there is some evidence to suggest that they may be able to differentiate between those individuals with SCI who cognitively decline over time and those who do not. While this finding has potential clinical implications, achieving optimal predictive value will likely require further research into the use of numerous biomarkers in combination. [ABSTRACT FROM AUTHOR]

Psychosis is relatively common in later life and can present in a wide variety of contexts, including early-onset and late-onset schizophrenia, delusional disorder, mood disorders, and various dementias. It can also occur as the result of numerous medical and neurological diseases and from the use of certain medications. Although identifying the cause of psychosis in older patients can be challenging, the unique clinical features associated with the different disorders can help inmaking the diagnosis. Accurate diagnosis of psychosis in older populations is essential, as its treatment varies depending on the context in which it appears. Despite the safety concerns regarding the use of antipsychotics in older patients, certain pharmacological treatments appear to be both efficacious and reasonably safe in treating psychosis in older populations. Additionally, although research is limited, numerous psychosocial therapies appear promising. This review summarizes the literature on the epidemiology, clinical characteristics, neuroimaging, and treatment of psychosis in later life, and serves as an update to past reviews on this topic. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a prevalent and currently incurable brain disease whose impact will continue to rise as the population ages. With limited treatment options, a variety of experimental therapies are currently in clinical trials. EVP-6124 (encenicline) is an α7 nicotinic acetylcholine receptor partial agonist under investigation for the symptomatic treatment of AD. EVP-6124 activates the α7 nicotinic acetylcholine receptor at low nanomolar brain concentrations and improves memory performance in rats. Treatment with EVP-6124 in Phase I and II trials involving patients with mild-to-moderate AD was well tolerated and showed statistically significant improvements compared with placebo on cognitive and functional measures. Two Phase III trials under the title COGNITIV AD will assess the efficacy and tolerability of EVP-6124 in patients with mild-to-moderate AD. Based on the completed clinical trials and proposed mechanism of action, EVP-6124 would appear to be a good candidate for therapy in combination with cholinesterase inhibitors. [ABSTRACT FROM AUTHOR]

Aims The 24-week, prospective, randomized, double-blind ACTION study investigated the efficacy, safety, and tolerability of 13.3 versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease ( AD). Methods Patients had probable AD and Mini-Mental State Examination scores ≥3-≤12. Primary outcome measures were as follows: Severe Impairment Battery ( SIB) and AD Cooperative Study-Activities of Daily Living scale-Severe Impairment Version ( ADCS- ADL- SIV). Secondary outcomes were as follows: ADCS-Clinical Global Impression of Change ( ADCS- CGIC), 12-item Neuropsychiatric Inventory ( NPI-12), and safety/tolerability. Results Of 1014 patients screened, 716 were randomized to 13.3 mg/24 h (N = 356) or 4.6 mg/24 h (N = 360) patch. Baseline characteristics/demographics were comparable. Completion rates were as follows: 64.3% (N = 229) with 13.3 mg/24 h and 65.0% (N = 234) with 4.6 mg/24 h patch. The 13.3 mg/24 h patch was significantly superior to 4.6 mg/24 h patch on cognition ( SIB) and function ( ADCS- ADL- SIV) at Week 16 ( P < 0.0001 and P = 0.049, respectively) and 24 (primary endpoint; P < 0.0001 and P = 0.025). Significant between-group differences (Week 24) were observed on the ADCS- CGIC ( P = 0.0023), not NPI-12 ( P = 0.1437). A similar proportion of the 13.3 mg/24 h and 4.6 mg/24 h patch groups reported adverse events ( AEs; 74.6% and 73.3%, respectively) and serious AEs (14.9% and 13.6%). Conclusions The 13.3 mg/24 h patch demonstrated superior efficacy to 4.6 mg/24 h patch on SIB and ADCS- ADL- SIV, without marked increase in AEs, suggesting higher-dose patch has a favorable benefit-to-risk profile in severe AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive, degenerative brain disease. The mainstay of current management of patients with AD involves drugs that provide symptomatic therapy. Two classes of medications have been approved by the US FDA for the treatment of AD: the cholinesterase inhibitors (ChEIs), which include galantamine and rivastigmine (both approved for use in mild to moderate AD) and donepezil (approved for use in mild to severe AD); and the non-competitive NMDA receptor antagonist memantine (approved for use in moderate to severe AD). The European and Asian regulatory bodies have also approved ChEIs as monotherapy in mild to moderate AD. Future research directions are mostly focusing on disease modification and prevention. This review covers key studies of the efficacy, safety and tolerability of combination therapy in AD, defined as a combination of the NMDA receptor antagonist memantine with any of the ChEIs (donepezil, galantamine or rivastigmine) for the treatment of AD. Relevant studies were identified via a PubMed search. This review shows that combination therapy for AD seems to be safe, well tolerated and may represent the current gold standard for treatment of moderate to severe AD and possibly mild to moderate AD as well. [ABSTRACT FROM AUTHOR]

Objective: In Alzheimer’s disease (AD), rivastigmine has demonstrated statistically significant efficacy versus placebo on cognition and activities of daily living (ADL). The aim of this retrospective analysis was to further evaluate the treatment effects of rivastigmine on individual ADL items. Methods: This exploratory analysis focused on the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) outcome from a large, international, 24-week, controlled trial of rivastigmine once-daily transdermal patch and twice-daily capsules in AD (CENA713D2320, NCT00099242). Percentages of patients ‘‘improving’’ or ‘‘not worsening’’ on individual ADL items were calculated and changes from baseline with rivastigmine versus placebo were evaluated. Results: Patients received rivastigmine patch (9.5 mg/24 h; n=247), capsule (12 mg/day; n=254), and placebo (n=281). Statistically significant changes from baseline in composite ADCS-ADL scores in both rivastigmine treatment groups versus placebo ( p<0.05) had previously been reported. In this responder analysis of the subset of patients who showed baseline functional impairments on each item, statistically significant differences favoring rivastigmine were seen on the following functions: bathing, clearing dishes, obtaining a beverage, garbage disposal, traveling, shopping, writing, using household appliances, and talking about current events. A responder analysis of emergence of ADL impairment was not as sensitive to treatment effects. Conclusions: These findings suggest that rivastigmine may benefit specific ADL, particularly in patients who are already exhibiting functional impairment. Further research is required to improve understanding of how drugs such as rivastigmine exert their clinical effects. Copyright # 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive, degenerative brain disease. Currently available US FDA-approved pharmacological management options for AD are cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N-methyl-D-aspartate receptor antagonist (memantine). These treatment options may provide symptomatic benefits. Medication adherence is one of the many problems faced by the caregivers of patients with dementia. The currently available FDA-approved memantine immediate-release (IR) has been found safe and efficacious at a dose of 10 mg twice daily (20 mg/day) both as monotherapy and in combination with cholinesterase inhibitors in moderate to severe dementia. Memantine extended-release (ER) 28 mg, a new once-daily form at a higher dose, has also been found to be safe and well tolerated in 2 studies: one in 24 healthy volunteers which showed relatively minor fluctuation in plasma levels of memantine during the steady-state dosing interval and second, a multinational multi-center study, comparing memantine ER 28 mg and placebo in patients with moderate to severe AD stable on concurrent cholinesterase inhibitor (ChEI). In this study, memantine ER was found to be an efficacious drug with a good safety and tolerability profile. Both memantine IR 20 mg and memantine ER 28 mg are now FDA-approved for the treatment of moderate to severe AD, either alone, or in combination with a ChEI. Both are efficacious, safe, and well tolerated. Medication adherence with the ER preparation should improve because of once-daily dosing. There is a possibility of superior efficacy of the higher dose memantine ER (28 mg) over the currently approved dosage of memantine IR (20 mg). However, further randomized, controlled, double-blind comparator studies of memantine ER 28 mg vs memantine IR 20 mg and/or 30 mg in single and/or divided doses are required to assess the possible benefits of memantine ER over memantine IR. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) patients treated with rivastigmine transdermal patch have shown statistically significant differences versus placebo on the AD Assessment scale-cognitive subscale (ADAS-cog). In this retrospective analysis of a double-blind, placebo- and active-controlled, 24-week clinical trial, the specific effects of rivastigmine patch on individual ADAS-cog items and cognitive domains (memory, language, and praxis) were explored. The mean baseline to week 24 changes were calculated for each ADAS-cog item and domain in this exploratory, hypothesis-generating analysis. Patients on 9.5 mg/24 h rivastigmine patch, 17.4 mg/24 h rivastigmine patch, and 3 to 12 mg/d rivastigmine capsules showed improvements over placebo on the memory and praxis ADAS-cog subscales. The rivastigmine patch groups also showed improvements on the language subscale. Significant differences versus placebo were seen on several individual item scores in the rivastigmine-treated groups. Rivastigmine patch was associated with improvements on the memory, praxis, and language domains of cognition in patients with mild-to-moderate AD. [ABSTRACT FROM PUBLISHER]

The article presents a study on Alzheimer's disease (AD) and long-term care. It reviews the natural history of the AD and who is at risk while describing early signs and symptoms of the disease that one should be aware of in residents of long-term care (LTC) facilities. It stresses the importance of recognizing the early signs and symptoms of AD in LTC facilities for proper diagnosis, care, and treatment of residents, improving their quality of life.

Circadian Rhythm Disturbances (CRDs) affect as many as a quarter of Alzheimer's disease (AD) patients during some stage of their illness. Alterations in the suprachiasmatic nucleus and melatonin secretion are the major factors linked with the cause of CRDs. As a result, the normal physiology of sleep, the biological clock, and core body temperature are affected. This paper systematically discusses some of the causative factors, typical symptoms, and treatment options for CRDs in patients with AD. This paper also emphasizes the implementation of behavioral and environmental therapies before embarking on medications to treat CRDs. Pharmacotherapeutic options are summarized to provide symptomatic benefits for the patient and relieve stress on their families and professional care providers. As of today, there are few studies relative to CRDs in AD. Large randomized trials are warranted to evaluate the effects of treatments such as bright light therapy and engaging activities in the reduction of CRDs in AD patients. [ABSTRACT FROM AUTHOR]

Memantine is a moderate-affinity, uncompetitive antagonist of N-methyl-D-aspartate receptors, approved for the treatment of moderate to severe Alzheimer’s disease (AD). Available data suggest that, in addition to its benefits on cognition, function, and global status, memantine treatment may also help alleviate behavioral symptoms. This article provides an overview of the prevalence, assessment, and treatment of behavioral disturbances in AD, and summarizes current knowledge regarding the effects of memantine on the behavior of community-dwelling patients. We searched EMBASE and PubMed (January 1992 to October 2008) for reports on memantine trials that involved outpatients with moderate to severe AD. All previously unpublished data were obtained from Forest Laboratories, Inc. Behavioral outcomes were assessed in three completed, double-blind, placebo-controlled trials.Overall, patients who received memantine performed better on behavioral measures than those treated with placebo. Post-hoc analyses suggest that memantine treatment was associated with a reduced severity or emergence of specific symptoms, particularly agitation and aggression. Prospective, well-designed trials are warranted to evaluate the efficacy of memantine in patients with significant behavioral symptoms. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Progressive deterioration in cognitive function and the ability to perform activities of daily living are the hallmarks of Alzheimer's disease (AD). As the disease progresses and behavioural/neuropsychiatric symptoms become more predominant, carers of AD patients themselves encounter a raft of physical, emotional, social and financial problems. Appropriate therapeutic management of AD patients, particularly their behavioural symptoms, may reduce the burden placed on family and professional caregivers. Preservation of cholinergic neuro- transmission by cholinesterase inhibitors is the mainstay of pharmacological therapy for AD. Rivastigmine, a dual inhibitor of acetylcholinesterase and butyrylcholinesterase, has pharmacological properties that appear particularly favourable regarding the behavioural symptoms of AD. In addition to its beneficial effects on cognitive and global function, rivastigmine treatment in mild-to- moderate AD is associated with improvements in behavioural symptoms, a decreased requirement for antipsychotic drugs and delays in nursing home placement; reductions in caregiver burden, caregiver time and costs have also been reported. Rivastigmine treatment has also demonstrated improvements in behavioural symptoms and reductions in psychotropic medication usage in nursing home residents with moderate-to-severe AD, and may be associated with a reduction in professional caregiver burden. In summary, the positive effects of rivastigmine on functional and behavioural symptoms of AD help to reduce the time, stress and overall burden associated with caregiving, both in the informal home care and nursing home environments. [ABSTRACT FROM AUTHOR]

The article discusses diagnostic and referral issues in Alzheimer's disease (AD). It stresses the importance of early diagnosis, aggressive therapy and specialized care of AD. It reveals that AD is the most common cause of dementia in the elderly. Steps in identifying dementia are outlined. It cites the growing importance of multidisciplinary care of AD.

Disability, characterised by the loss of ability to perform activities of daily living (ADL), is a defining feature of dementia that results in growing caregiver burden and the eventual need for alternative care or nursing home placement. Functional decline in patients with dementia can also result from causes other than dementia, such as comorbid medical and psychiatric illnesses and sensory impairment. ADL consists of instrumental ADL (IADL) [complex higher order skills, such as managing finances] and basic ADL (BADL) [self-maintenance skills, such as bathing]. Assessment of IADL and BADL is recommended to establish a diagnosis of dementia. Functional assessment also helps the healthcare provider to offer appropriate counselling regarding safety concerns and need for custodial care. Functional capacity measures have been used increasingly in pharmacological trials of patients with Alzheimer's disease (AD) and related dementias, although at the present time these measures are generally not primary outcome measures. Functional impairment is not a uniform construct; rather, it is multifaceted and can be measured with various clinical instruments. Many scales have been validated for use in patients with AD for characterising functional impairment and evaluating the efficacy of treatment. Research to date indicates that cholinesterase inhibitors have the potential for modest but meaningful beneficial effects on ADL in patients with mild-to-moderate AD. Memantine also has promising beneficial effects on functional abilities in persons with moderate-to-severe AD. Assessment of ADL as a primary efficacy measure using a validated scale that is non-gender biased and cross-nationally relevant is recommended in new treatment trials of patients with AD and related dementias. [ABSTRACT FROM AUTHOR]

Background: Cholinesterase (ChE) inhibitors currently used in the treatment of Alzheimer''s disease (AD) are the acetylcholinesterase (AChE)-selective inhibitors, donepezil and galantamine, and the dual AChE and butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic and pharmacodynamic properties, and these differences could significantly impact on safety, tolerability, and efficacy.Objective: The aim of this article was to provide an overview of the ChE inhibitors widely used in AD, focusing on key pharmacologic differences among agents and how these may translate into important differences in safety, tolerability, and efficacy in clinical practice.Methods: Using published literature collected over time by the author, a review was conducted, focusing on the pharmacology and clinical data of donepezil, galantamine, and rivastigmine.Results: All ChE inhibitors have the potential to induce centrally mediated cholinergic adverse events (AEs), such as nausea and vomiting, if the dose is increased too rapidly or in increments that are too large. These AEs, which are most likely to occur during the “getting on,” or dose-escalation, phase of treatment, may result in patients discontinuing treatment early without achieving optimum therapeutic benefit. To reduce the incidence of these AEs, a slow dose-escalation schedule has been established in clinical practice, consisting of a “start low, go slow” procedure with a minimum of 4 weeks between dose increases. After “getting on” treatment, maintaining treatment in the long term, or “staying on,” may be achieved with good safety, tolerability, and sustained symptomatic efficacy across the key symptom domains (activities of daily living, behavior, and cognition).Conclusions: ChE inhibitors provide symptomatic benefit in AD across key symptom domains. Factors influencing the safety, tolerability, and efficacy of these agents in clinical practice include ChE enzymes inhibited, brain and brain-region ChE selectivity, and metabolism route. Class-specific cholinergic AEs can be minimized using slow, flexible dose escalation. [Copyright &y& Elsevier]

Talks about management of Alzheimer's disease (AD). Counseling regarding specific issues in AD; Pharmacotherapy of AD; Treatment of behavioral and psychological symptoms of AD; Nonpharmacological interventions.

Alzheimer's disease (AD) is often associated with multiple comorbidities and subsequent polypharmacy. Treatment of AD with acetylcholinesterase (AChE) inhibitors can carry a risk of drug interaction with multiple medications often prescribed for other co-existing illnesses. Rivastigmine is an AChE inhibitor that is enzymatically cleaved by AChE, minimally metabolized by cytochrome P450 enzymes, has low protein binding, has a short plasma half-life, and a relatively short duration of action. Such properties make it ideal for use in this patient population. A pharmacodynamic analysis of rivastigmine administered concomitantly with other medications (22 different therapeutic classes) did not reveal any significant pattern of increase in adverse events that would indicate a drug interaction. In summary, rivastigmine was well tolerated and safely administered to a population receiving multiple medications for ‘real-world’ comorbidities. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Seventy percent to 90% of all nursing home residents have one or more DSM-IV diagnosable psychiatric disorders with the dementias, largely Alzheimer's disease (AD) and its secondary behavioral disturbances. The presence of agitation/aggressivity, psychosis, or mood disturbance in the context of AD is the number one reason for psychiatric consultation in the nursing home. Nearly 80% of AD patients will develop agitation, 40% will experience depression, and 33% will manifest psychotic symptoms. This article will focus on evaluation and management of these disturbances. [ABSTRACT FROM AUTHOR]

Little is known about the drinking habits of individuals who develop Alzheimer's disease. A pilot survey of 84 autopsy­confirmed Alzheimer cases was carried out to explore a possible role of alcohol consumption in the onset and duration of Alzheimer's disease. Information on the drinking habits of deceased patients for a 15-year period prior to the onset of the disease was obtained from a surrogate respondent (next of kin) and from the patients' medical records. Alzheimer patients' drinking patterns were comparable to those of the general population. Patients with a history of alcohol abuse did not develop Alzheimer's disease at an earlier age than abstainers or occasional, light or moderate drinkers. Although not statistically significant, duration of survival in Alzheimer's disease was a few years shorter in patients with a history of alcohol abuse, [ABSTRACT FROM AUTHOR]

The article presents information on Alzheimer's disease (AD). AD is defined as a progressive neurodegenerative disease chararacterized by loss of memory, a decline in activity to perform daily activities and changes in personality, behavior and cognition. It is estimated that about 5 million adults are affected by AD in the U.S. It reveals that AD is the most prevalent form of irreversible dementia.

Provides information on two drugs for treating Alzheimer's disease (AD) or dementia that offer advantages over other therapies.

The article discusses various reports published within the issue, including one on the phenomenon of tau-mediated neurotoxicity and another on evidence-based approaches to preventing Alzheimer's disease.

The search for effective treatments of Alzheimer’s disease (AD) is one of the major challenges facing modern medicine. Acetylcholinesterase (AChE) inhibitors (AChEIs) are effective for the treatment of mild to moderate AD, and memantine, an N-methyl-D-aspartate (NMDA) inhibitor, has been approved for moderate to severe AD. Galantamine is of particular interest because it has a dual mechanism of action: it is postulated to be both an AChEI and an allosteric modulator of nicotinic receptors. Modulation of NMDA and nicotinic receptors by memantine and galantamine may provide an optimal combination therapy for AD. The cholinergic and glutamatergic neurotransmitter systems, which share a close functional relationship, may play a role in the pathogenesis of AD. Close examination of the pharmacology of the 2 compounds suggests that galantamine can augment memantine’s glutamatergic noise suppression while simultaneously enhancing the physiologic glutamatergic signal. The link between these systems suggests that AD therapies, which capitalize on this relationship, may be more effective in improving cognition than approaches focusing on a single system. [ABSTRACT FROM PUBLISHER]

A combination of cholinergic and glutamatergic dysfunction appears to underlie the symptomatology of Alzheimer’s disease. Therefore, one hypothesis is that treatment strategies should address impairments in both systems. Galantamine is an acetylcholinesterase inhibitor that, unlike other acetylcholinesterase inhibitors, has a postulated dual mode of action as a nicotinic receptor modulator. Galantamine has demonstrated long-term efficacy in improving or maintaining cognition, functionality, and behavior in patients with mild to moderate Alzheimer’s disease. Memantine, a noncompetitive N-methyl-D-aspartate-receptor antagonist, reduces deterioration in cognition and function in patients with moderate to severe Alzheimer’s disease. Pharmacokinetic and pharmacodynamic as well as ongoing observation studies support the concept of adjunctive therapy with memantine in patients with advanced moderate Alzheimer’s disease currently treated with an established galantamine regimen. The potential to modulate both acetylcholine and glutamate pathways in Alzheimer’s disease presents a novel treatment strategy for the management of mild to moderately severe Alzheimer’s disease. [ABSTRACT FROM PUBLISHER]

Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care. Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters. An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health. Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world. This conclusion is in keeping with the position of the United States' Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient's right. The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline. [ABSTRACT FROM AUTHOR]

Agitation and aggression are frequently occurring and distressing behavioral and psychological symptoms of dementia (BPSD). These symptoms are disturbing for individuals with Alzheimer disease, commonly confer risk to the patient and others, and present a major management challenge for clinicians. The most widely prescribed pharmacological treatments for these symptoms-atypical antipsychotics-have a modest but significant beneficial effect in the short-term treatment (over 6-12 weeks) of aggression but limited benefits in longer term therapy. Benefits are less well established for other symptoms of agitation. In addition, concerns are growing over the potential for serious adverse outcomes with these treatments, including stroke and death. A detailed consideration of other pharmacological and nonpharmacological approaches to agitation and aggression in patients with Alzheimer disease is, therefore, imperative. This article reviews the increasing evidence in support of psychological interventions or alternative therapies (such as aromatherapy) as a first-line management strategy for agitation, as well as the potential pharmacological alternatives to atypical antipsychotics-preliminary evidence for memantine, carbamazepine, and citalopram is encouraging. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to determine the prevalence of uncorrected visual disorders in nursing home patients with Alzheimer’s disease (AD) and to determine whether appropriate corrective measures were taken by nursing home staff. This study was conducted at 2 community nursing homes in the St Louis area. Whereas previous studies have shown that visual impairment is common among all residents of nursing facilities, our study was focused specifically on residents with AD. This population is less able to effectively express needs and more likely to endure unaddressed visual deficits. For AD patients, it is important to offer appropriate corrective remedies in order to maintain as much functional independence as possible. Methods: A retrospective cohort study was conducted in 2 private, skilled nursing facilities in St Louis County thought to be representative of community nursing homes in the United States. All subjects were patients with a diagnosis of dementia of probable AD. Demographic information collected included age, sex, and race. Mini-Mental State Examination scores were also obtained. The patients, their families, and nursing staff were interviewed to determine the patients’ visual history, corrective measures, and the usage of corrective eyewear before and after admission to the nursing homes. The data were summarized to demonstrate how many patients suffered from uncorrected errors of refraction and what factors contributed to their visual status. Results: Of the total of 85 patients included in the study, 80 (94.1%) required glasses for correction of presbyopia, myopia, or both. However, 25 of the 80 residents had not actively been using glasses since entering the nursing home. Of these 25 residents not wearing proper eyewear, 9 residents were too cognitively impaired to request them, 8 residents had broken or misplaced them, and 8 residents had prescriptions that were no longer sufficient to correct their vision. Discussion: Our study found that nearly one third of the visually impaired nursing home residents with AD (25 of 80 patients) were not using their required eyewear. These 25 patients were the population of most interest because they were most likely to benefit from intervention. Many of these patients were not using glasses because they had been lost, damaged, or were no longer sufficient to correct their vision. Conclusions: We have presented 3 recommendations intended to prevent uncorrected visual acuity in nursing home residents with dementia: (1) Label eyewear in appropriate patient populations to provide rapid identification in the event of misplacement, (2) recommend that an extra pair of glasses be made available if the current pair would be lost or damaged, and (3) ensure that all residents have annual or biannual eye exams. If adequate steps are taken to prevent unnecessary visual impairment in AD patients, it would limit their dependence on others, reduce the burden on nursing staff, and improve the patients’ overall quality of life. [Copyright &y& Elsevier]