Alzheimer Disease: Reichman WE

Fillit HM, Doody RS, Binaso K, Crooks GM, Ferris SH, Farlow MR, Leifer B, Mills C, Minkoff N, Orland B, Reichman WE, Salloway S. · Alzheimer's Drug Discovery Foundation and Institute for the Study of Aging New York, New York 10019, USA. · Am J Geriatr Pharmacother. · Pubmed #17157793 No free full text.

Abstract: BACKGROUND: Alzheimer's disease and related dementias (ADRDs) are increasingly recognized as important causes of impaired cognition, function, and quality of life, as well as excess medical care utilization and costs in the elderly Medicare managed care population. Evidence-based clinical practice guidelines for ADRDs were published in 2001. More recent studies have resulted in the approval of new agents and demonstrated an expanded role for antidementia therapy in various types of dementia, settings of care, stages of disease, and the use of combination therapy. However, these clinical guidelines have not been updated in the past few years. OBJECTIVE: The goal of this article was to provide practical recommendations developed by a panel of experts that address issues of early diagnosis, treatment, and care management of ADRDs. The panel also addressed the societal and managed care implications. METHODS: A panel of leading experts was convened to develop consensus recommendations for the treatment and management of dementia based on currently available evidence and the panel's informed expert opinion. The panel comprised 12 leading experts, including clinical investigators and practitioners in geriatric medicine, neurology, psychiatry, and psychology; managed care medical and pharmacy directors; a health systems medical director; and a health policy expert. In addition, articles were collected based on PubMed searches (2000-2005) that were relevant to the key issues identified. Search terms included Alzheimer's disease, dementia, clinical practice guidelines, clinical trials, screening and assessment, and managed care. RESULTS: ADRDs represent a significant clinical and economic burden to individuals and society, including Medicare managed care organizations (MCOs). Appropriate utilization of antidementia therapy and care management is vitally important to achieving quality of life and care for dementia patients and their caregivers, and for managing the excess costs of Alzheimer's disease. The recommendations address relevant, practical, and timely concerns that are faced on a daily basis by practitioners and by Medicare MCO medical management programs in the care of dementia patients. These consensus recommendations attempt to describe a reasonable current standard for the provision of quality care for patients with dementia. The panel recommendations support the use of screening for cognitive impairment and the use of antidementia therapy for ADRDs in different stages of disease and types of dementia in all clinical settings. The panel members evaluated the use of the 3 marketed cholinesterase inhibitors-donepezil, galantamine, and rivastigmine-as well as the N-methyl-D-aspartate antagonist memantine. Recommendations for using these medications are made with an appreciation of the difficulties in translating the results from investigational clinical trials into clinical practice. CONCLUSIONS: The recommendations of the expert panel represent a clear consensus that nihilism in the diagnosis, treatment, and management of ADRDs is unwarranted, impairs quality of care, and is ultimately not costeffective.

Shah S, Reichman WE. · Correspondence: Shailaja Shah UMDNJ-RobertWood Johnson Medical School, 667 Hoes Lane, Piscataway, NJ 08854, USA. · Clin Interv Aging. · Pubmed #18044110 links to  free full text

Abstract: Alzheimer's disease (AD) is the most common cause of dementia affecting nearly 18 million people around the world and 4.5 million in the US. It is a progressive neurodegenerative condition that is estimated to dramatically increase in prevalence as the elderly population continues to grow. As the cognitive and neuropsychiatric signs and symptoms of AD progresses in severity over time, affected individuals become increasingly dependent on others for assistance in performing all activities of daily living. The burden of caring for someone affected by the disorder is great and has substantial impact on a family's emotional, social and financial well-being. In the US, the currently approved medications for the treatment of mild to moderate stages of AD are the cholinesterase inhibitors (ChEIs). Cholinesterase inhibitors have shown modest efficacy in terms of symptomatic improvement and stabilization for periods generally ranging from 6 to 12 months. There are additional data that have emerged, which suggest longer-term benefits. For the moderate to severe stages of AD, memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist is in widespread use and has shown modest benefit as monotherapy and in combination with ChEIs. The cost effectiveness of the currently available therapeutic agents for AD has undergone great scrutiny and remains controversial, especially outside the US. Neuropsychiatric symptoms such as agitation and psychosis are common in AD. Unfortunately, in the US there are no Food and Drug Administration (FDA)-approved agents for the treatment of these symptoms, although atypical antipsychotics have shown some efficacy and have been widely used. However, the use of these agents has recently warranted special caution due to reports of associated adverse effects such as weight gain, hyperlipidemia, glucose intolerance, cerebrovascular events, and an increased risk for death. Alternative agents used to treat neuropsychiatric symptoms include serotonergic antidepressants, benzodiazepines, and anticonvulsant medications.

Reichman WE. · No affiliation provided · Am J Manag Care. · Pubmed #11142177 links to  free full text

Abstract: Comprehensive treatment of Alzheimer's disease (AD) requires thorough caregiver support and a thoughtful and informed use of medications for cognition enhancement, neuroprotection, and the treatment of disturbed behavior. Current treatments such as the cholinesterase inhibitors donepezil and rivastigmine can slow the progression of cognitive and functional deficits in AD over the short term. Sustained improvement and possible disease modification that result from the use of these medications are being evaluated in long-term studies. Treatment with alpha-tocopherol (vitamin E) has been shown to delay the progression of nursing home admission in patients with mild-to-moderate AD. Although antioxidant, anti-inflammatory, and other treatment strategies are promising, recent studies of the treatment of AD with estrogen or prednisone have produced disappointing results. For managing the behavioral symptoms that commonly accompany AD (e.g., delusions, aggression, depression, anxiety, irritability), various antipsychotics, antidepressants, and anticonvulsants have been effective in carefully selected patients.

Lyketsos CG, Reichman WE, Kershaw P, Zhu Y. · Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Osler 320, 600 North Wolfe Street, Baltimore, MD 21287, USA. · Am J Geriatr Psychiatry. · Pubmed #15353385 No free full text.

Abstract: OBJECTIVE: The authors evaluated the long-term safety, efficacy, and tolerability of galantamine 24 mg/day in the treatment of Alzheimer disease by means of a 12-month, open-label extension of an earlier 5-month, double-blind, placebo-controlled trial with a 6-week withdrawal phase. METHODS: Patients completing two double-blind, placebo-controlled trials (N=699) were escalated to a 24-mg dose (12 mg bid) of galantamine during a period of 2 weeks and treated for 12 months beyond the initial 6.5-month, double-blind period (total treatment duration: 18.5 months). The primary efficacy measure was the change from baseline in the Alzheimer's Disease Assessment Scale (ADAS-Cog/11) score at 18.5 months; secondary endpoints included total scores on the Alzheimer's Disease Cooperative Study of Activities of Daily Living and the Neuropsychiatric Inventory. Standard safety evaluations, including adverse-event monitoring, were performed. RESULTS: Patients taking galantamine continuously throughout the double-blind and open-label studies (N=288) showed sustained cognitive benefits on ADAS-Cog/11 scores at 18.5 months. Patients were maintained close to baseline cognitive ability for 12 months, and safety was as expected and documented in other large studies of galantamine. Analysis of the subgroup of patients (N=113) who completed the entire 18.5 months of galantamine treatment showed that cognitive function was maintained up to 14 months. CONCLUSIONS: Results of this open-label extension support the findings from previous galantamine studies and demonstrate the safety and tolerability of galantamine for up to 18.5 months.

Relkin NR, Reichman WE, Orazem J, McRae T. · Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 428 East 72nd Street, Suite 500, New York, N.Y. 10021, USA. · Dement Geriatr Cogn Disord. · Pubmed #12714795 No free full text.

Abstract: This phase III trial was conducted to evaluate the safety and efficacy of donepezil in Alzheimer's disease (AD) patients with a greater range of comorbid conditions and concomitant medication use than those previously evaluated in placebo-controlled studies. Patients (n = 1,035) with mild to moderate probable or possible AD were enrolled from 255 sites in the USA; 894 (86%) completed the trial. Mean age was 74.9 years (+/- 7.8); baseline standardized Mini-Mental State Examination (sMMSE) score was 19.77 (+/- 5.4). Nearly all patients had at least 1 prior or comorbid medical condition (97%) or were taking at least 1 concomitant medication (93%). Safety assessments included recording treatment-emergent adverse events (AEs). To confirm comparability with past studies, efficacy was measured using the sMMSE. Over the 12-week study period, the mean sMMSE score increased by 1.54 points over baseline (p < 0.0001) in donepezil-treated patients. Most AEs (64%) were mild, and the occurrence of cholinergic-induced AEs was significantly lower after a dose increase at 4 weeks than that seen with a dose increase after 1 week in previous trials. Risk ratios for gastrointestinal side effects were not significantly increased by the use of aspirin or nonsteroidal anti-inflammatory drugs. Risk ratios for bradycardia were not significantly increased by the use of beta-blockers, nondihydropyridine calcium channel blockers or digoxin. Therefore, donepezil improved cognition, as measured by the sMMSE, and was well tolerated despite high concomitant medication use and extensive comorbidity. These results highlight donepezil as a safe and effective treatment for AD patients typically seen by community-based physicians.

Reichman WE, Negron A. · University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08855, USA. · Int J Geriatr Psychiatry. · Pubmed #11748784 No free full text.

Abstract: Negative symptoms are a well-documented, intensively studied feature of schizophrenia. In recent years, however, increasing attention has been directed to the prominence of these symptoms in elderly patients suffering from dementia. Behavioral alterations such as avolition, apathy, social withdrawal and emotional disengagement appear to be commonly found in patients suffering from Alzheimer's disease. A consistent research finding is that negative symptoms in dementia cannot be solely accounted for by depression; they represent a separate symptomatic cluster. An area of ongoing investigation is the relationship of negative symptoms to the functional impairment of dementia. It has been hypothesized that negative symptoms may contribute to the functional impairment caused by cognitive deterioration. Recently, it was reported that negative symptoms in dementia are responsive to pharmacotherapy with an atypical antipsychotic agent. This treatment effect appeared to be independent of effects on positive symptoms. As dementia continues to be a major public health concern, the phenomenology of negative symptoms in the elderly and the treatment of these symptoms are likely to remain areas of active investigation.

Negrón AE, Reichman WE. · Department of Psychiatry, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway 08855, USA. · Int Psychogeriatr. · Pubmed #11263718 No free full text.

Abstract: INTRODUCTION: Negative symptoms such as diminished initiative, drive, motivation, and emotional reactivity have been described in patients with Alzheimer's disease (AD). The purpose of this study was to retrospectively analyze the efficacy and tolerability of risperidone for the treatment of clinically significant positive and negative symptoms in AD. METHODS: We reviewed the charts of 50 community-residing AD patients who had been treated in a specialized university-based dementia management clinic. Clinical data comparing baseline and 12 weeks of treatment were obtained by reviewing a series of rating scales that were recorded as part of a comprehensive behavioral assessment. RESULTS: Reviewed subjects had a mean age of 79.7 6 years and a mean of 12 +/- 3.6 years of school. Seventy percent of the subjects were female and the majority was White. The mean dose of risperidone prescribed was 1.3 +/- 0.6 mg per day (range from 0.5 mg to 3.0 mg). After 12 weeks of treatment, the severity of positive and negative symptoms was significantly reduced. Importantly, improvement in negative symptoms with the use of risperidone appeared to be independent of a positive treatment effect on positive symptoms. Risperidone had insignificant effects on both cognitive status and the emergence of extrapyramidal symptoms. CONCLUSION: This retrospective study demonstrates that risperidone appears to be efficacious in the treatment of clinically significant positive and negative symptoms in patients with AD.