Alzheimer Disease: Fillit HM

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.

Horton AR, Fillit HM. · No affiliation provided · Curr Alzheimer Res. · Pubmed #18220510 No free full text.

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Fillit HM, Refolo LM. · The Institute for the Study of Aging, 1414 Avenue of the Americas, Suite 1502, New York, NY, USA. · Curr Alzheimer Res. · Pubmed #15974904 No free full text.

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Refolo LM, Fillit HM. · No affiliation provided · J Alzheimers Dis. · Pubmed #15665407 links to  free full text

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Refolo LM, Fillit HM. · The Institute for the Study of Aging, New York, NY, USA. · J Mol Neurosci. · Pubmed #15314243 No free full text.

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Fillit HM, Refolo LM. · The Institute for the Study of Aging, New York, NY, USA. · J Mol Neurosci. · Pubmed #12540049 No free full text.

This publication has no abstract.

Refolo LM, Fillit HM. · Institute for the Study of Aging, New York, NY 10153, USA. · J Mol Neurosci. · Pubmed #15181243 No free full text.

Abstract: The identification of factors that influence the onset or progression of the sporadic form of Alzheimer's disease (AD) is a key step toward understanding its mechanism(s) and developing successful rational therapies. The apoE genotype has been identified as a powerful risk factor for AD that may account for as much as 50% of the sporadic form of the disease. As the major risk factor for late-onset AD, apolipoprotein E4 (apoE4) should be considered a good target for AD drug discovery. However, despite knowing for over a decade that apoE4 is detrimental to the disease process, we still remain uncertain about the molecular mechanisms subserving the risk-factor activity of apoE4. This, coupled with the fact that we know relatively little about the function(s) of apoE in brain, has presented a barrier to developing apoE-based therapeutics for AD. Progress has been made in understanding the neurobiology of apoE; a number of potentially overlapping functions have been ascribed, which include lipid transport, neuronal repair, dendritic growth, maintenance of synaptic plasticity, and anti-inflammatory activities. Until the gaps are filled in our understanding of the pathogenic function(s) of apoE4, therapeutic strategies targeting this protein will lag behind the development of other AD therapies. Putative pathological functions, or risk-factor activities, of apoE4 include its role in beta-amyloid deposition, neurofibrillary tangle formation, synaptic loss, lipid dysfunction, neuroinflammation, and oxidative stress.

Fillit HM. · The Institute for the Study of Aging, Inc, New York, NY 10153, USA. · Arch Intern Med. · Pubmed #12230415 links to  free full text

Abstract: Alzheimer disease (AD) is the most common form of dementia among the elderly. A higher prevalence of AD in women than in men suggests a link between gonadal hormone levels and AD. Increasing evidence supports a role for estrogen in brain regions involved in learning and memory and in the protection and regulation of cholinergic neurons, which degenerate in AD. Despite the lack of consensus, many studies indicate that hormone replacement therapy may decrease the risk for or delay the onset of AD in postmenopausal women. Recent trials have suggested that estrogen treatment may have no significant effect on the clinical course of AD in elderly women with the disease. Thus, the role of estrogen therapy seems to be confined to primary rather than secondary prevention of AD. Ongoing clinical studies may help to determine the role of estrogen in the cognitive function of postmenopausal women and in the prevention of AD.

Fillit HM, O'Connell AW, Brown WM, Altstiel LD, Anand R, Collins K, Ferris SH, Khachaturian ZS, Kinoshita J, Van Eldik L, Dewey CF. · The Institute for the Study of Aging, Inc., New York, New York, USA. · Alzheimer Dis Assoc Disord. · Pubmed #12070355 No free full text.

Abstract: Alzheimer disease (AD) is a neurodegenerative condition leading to progressive, irreversible loss of cognitive and behavioral function. Despite considerable investments in neuroscience research, only four drugs, all cholinesterase inhibitors, have been approved for the symptomatic management of AD in the United States. Although basically safe and modestly effective, these drugs are far from ideal, being neither universally efficacious nor disease modifying. AD exacts a considerable toll in direct medical costs, quality of life, and caregiver burden for persons and society. In addition to the obvious clinical benefit, therapeutic agents for AD and related dementias represent a considerable market opportunity for the pharmaceutical and biotechnology industries. There are currently 8-10 million AD sufferers in the seven major pharmaceutical markets. The market will grow rapidly in coming decades, as the developed world experiences an enormous increase in its elderly population. Given the great need for new therapeutic agents to manage and prevent AD, the Institute for the Study of Aging and the Fidelity Foundation organized a workshop, "Barriers to the Discovery and Development of Drugs for Alzheimer's Disease," to examine ways to expedite drug discovery and development. The identified barriers and potential solutions will be discussed here and in the accompanying articles in more detail.

Rice DP, Fillit HM, Max W, Knopman DS, Lloyd JR, Duttagupta S. · Institute for Health and Aging, University of California at San Francisco, 3333 California Street, Suite 340, San Francisco, CA 94118, USA. · Am J Manag Care. · Pubmed #11519239 links to  free full text

Abstract: BACKGROUND: The number of patients with Alzheimer's disease (AD) and related dementia treated in managed care organizations (MCOs) is increasing, and this trend is expected to continue. Therefore, it is critical that MCOs develop disease management strategies for this population. OBJECTIVE: To review the literature on the prevalence, costs, and treatment of AD and related dementia. STUDY DESIGN: Review of published articles from MEDLINE and peer-reviewed journals. RESULTS: Prevalence of AD and related dementia is approximately 5.7% among those aged 65 and older. Prevalence data from claims-based studies of AD in managed care are lower, ranging from 0.55% to 0.83%. Costs for formal care average $27,672 per patient annually, with long-term care being the most costly component. Annual costs for informal care are estimated to be $10,400 to $34,517 per patient. Additional costs associated with AD include lost wages and productivity of patients and caregivers and costs associated with increased morbidity of caregivers. Donepezil treatment is well tolerated and has been extensively tested and evaluated in clinical settings. Early diagnosis and treatment of AD with donepezil has been shown to slow cognitive decline in AD. Although study findings regarding the cost offsets of donepezil-treated patients to date are mixed, there is a growing body of evidence to support the inclusion of this and other therapies into an MCO's AD treatment armamentarium. CONCLUSIONS: It is unlikely that MCOs will escape the increased prevalence and costs associated with AD. Opportunities exist through patient management programs targeted toward early diagnosis, effective use of medications, control of comorbidities, and patient and family support to partially offset these costs while providing quality patient care.

Fillit HM. · No affiliation provided · Am J Manag Care. · Pubmed #11142179 links to  free full text

Abstract: Alzheimer's disease (AD) and dementia are responsible for high levels of excess per-member costs within managed care organizations (MCOs). To deal with anticipated increases in the prevalence of this disease within their populations, MCOs should take steps to integrate and target proven pharmacologic and non-pharmacologic AD treatments. Key areas of AD care improvement include protocol-driven diagnosis, referral, and treatment; education of primary care physicians and caregivers; development of an integrated case management approach; and use of validated measures to assess outcomes. Published evidence-based guidelines are available to assist MCOs in developing clinical protocols for diagnosis and treatment with effective agents such as cholinesterase inhibitors. Because of the opportunity to prevent costly hospitalizations and other complications as a result of medical and behavioral comorbidities, and because of the need for tightly integrated care, a disease management approach for AD may be justified.

Fillit HM. · No affiliation provided · Am J Manag Care. · Pubmed #11142178 links to  free full text

Abstract: Alzheimer's disease (AD), the leading cause of disability in people older than 75 years of age, has direct and indirect medical costs estimated at $100 billion per year. Yet underdiagnosis, coding, and reimbursement barriers result in most patients with AD receiving inadequate care. The vast majority of managed care organizations (MCOs) still lack formal disease management programs for AD. In several documented studies, the total costs for managing patients with AD increased significantly over age- and comorbidity-matched controls without AD. Importantly, these extra costs include not only nursing home care but also medical claims for inpatient stays, emergency department visits, and outpatient care. The extra costs are especially high in those patients with comorbidities such as diabetes or heart failure. Emerging pharmacoeconomic data indicate potential savings in medical care costs associated with early treatment of AD and the potential cost effectiveness of cholinesterase inhibitors such as donepezil. These studies document that Medicare MCOs are in need of directed efforts to improve medical management for members with AD.

Fillit HM, O'Connell AW, Refolo LM. · The Institute for the Study of Aging, New York, NY, USA. · J Mol Neurosci. · Pubmed #12212763 No free full text.

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Neumann PJ, Hammitt JK, Mueller C, Fillit HM, Hill J, Tetteh NA, Kosik KS. · Program on the Economic Evaluation of Medical Technology at the Harvard School of Public Health, Boston, Massachusetts, USA. · Health Aff (Millwood). · Pubmed #11558711 links to  free full text

Abstract: In a general population survey (N = 314), 79 percent of respondents stated that they would take a hypothetical genetic test to predict whether they will eventually develop Alzheimer's disease. The proportion fell to 45 percent for a "partially predictive" test (which had a one in ten chance of being incorrect). Inclination to obtain testing was similar across age groups. Respondents were willing to pay $324 for the completely predictive test. Respondents stated that if they tested positive, they would sign advance directives (84 percent), get their finances in order (74 percent), and purchase long-term care insurance (69 percent). Only a third of respondents expressed concern about confidentiality. The results suggest that people value genetic testingfor personal and financial reasons, but they also underscore the need to counsel potential recipients carefully about the accuracy and implications of test information.

Fillit HM, Gutterman EM, Brooks RL. · Institute for the Study of Aging, New York, New York 10153, USA. · Int Psychogeriatr. · Pubmed #11081959 No free full text.

Abstract: Comprehensive Alzheimer's disease (AD) treatment should address caregiver well-being. We predicted that caregiver burden would be lower among caregivers of AD patients who received donepezil relative to caregivers of patients not treated with donepezil. A self-administered, nationwide survey of AD caregivers was used to match caregivers of patients treated with donepezil (n = 274) to caregivers of patients not treated with donepezil (n = 274). The Caregiver Burden Scale measured time demands and distress linked to commonly performed caregiving tasks. Respondents were three-quarters female, with an average age of 60 years. Results demonstrated that donepezil caregivers reported significantly lower scores on difficulty of caregiving. This difference remained when statistical controls for multiple patient and caregiver variables were imposed. However, selection factors must be recognized as a possible explanation for differences. The groups reported no difference on the time-demand subscale. In conclusion, better management of AD symptoms through donepezil treatment may reduce the burden of caregiving, providing physicians with a pharmacologic approach to improving quality of life for AD patients and their families.