Alzheimer Disease: Tariot P

McQuillen MP, Tariot P. · No affiliation provided · Neurology. · Pubmed #15883305 No free full text.

This publication has no abstract.

Tariot P. · Univeristy of Rochester Medical Center, Rochester, NY, USA. · Expert Opin Pharmacother. · Pubmed #11825333 No free full text.

Abstract: Galantamine is a newly available cholinergic drug that offsets reductions in central cholinergic neurotransmission in Alzheimer's disease (AD) by specifically and reversibly inhibiting acetylcholinesterase (AChE) and by allosterically modulating nicotinic cholinergic receptors. The clinical impact of this latter mechanism of action has not been fully elucidated. Galantamine has favourable pharmacokinetic features including linear elimination kinetics, a relatively short half-life and high oral bioavailability. The efficacy of galantamine has been studied in an extensive clinical development program. During randomised, double-blind, placebo-controlled trials of up to 6 months' duration, galantamine 16 and 24 mg/day consistently produced a broad spectrum of beneficial effects on cognitive and non-cognitive AD symptoms. Patients' cognition, global function and abilities to perform both instrumental and basic activities of daily living were maintained, the emergence of behavioural symptoms was postponed and apparent reductions in caregiver burden were seen. In long-term studies (> or = 12 months), galantamine maintained cognitive and functional abilities at or near baseline levels for at least 12 months. Again, these benefits were associated with decreases in caregiver burden. The incidence of adverse events, which are typically mild or moderate in severity, is generally low with galantamine. Cholinergically mediated adverse events affecting mainly the gastrointestinal system can be minimised using the recommended slow dose-escalation regimen. Galantamine may therefore help reduce the overall burden and cost involved in caring for AD patients. Being approved for the treatment of mild-to-moderately severe AD in both the US and in Europe, with trials of its efficacy in other dementia types already yielding positive results, galantamine ranks as a first-line therapy for dementia.

Winblad B, Brodaty H, Gauthier S, Morris JC, Orgogozo JM, Rockwood K, Schneider L, Takeda M, Tariot P, Wilkinson D. · Karolinska Institutet, Alzheimer Research Center, Huddinge University Hospital, Stockholm, Sweden. · Int J Geriatr Psychiatry. · Pubmed #11466744 No free full text.

Abstract: The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease.

Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, Foster NL, Schneider LS, Sano M, Whitehouse P, Tariot P, Mellow AM, Auchus AP, Grundman M, Thomas RG, Schafer K, Thal LJ, Anonymous00040. · University of Washington, Department of Psychosocial and Community Health, Seattle 98195-7263, USA. · Neurology. · Pubmed #11087767 No free full text.

Abstract: BACKGROUND: Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs. OBJECTIVE: To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients. METHODS: A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden. RESULTS: Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments. CONCLUSIONS: Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.

Siemers ER, Quinn JF, Kaye J, Farlow MR, Porsteinsson A, Tariot P, Zoulnouni P, Galvin JE, Holtzman DM, Knopman DS, Satterwhite J, Gonzales C, Dean RA, May PC. · Eli Lilly and Company, Indianapolis, IN 46085, USA. · Neurology. · Pubmed #16505324 No free full text.

Abstract: LY450139 dihydrate, a gamma-secretase inhibitor, was studied in a randomized, controlled trial of 70 patients with Alzheimer disease. Subjects were given 30 mg for 1 week followed by 40 mg for 5 weeks. Treatment was well tolerated. Abeta(1-40) in plasma decreased by 38.2%; in CSF, Abeta(1-40) decreased by 4.42 +/- 9.55% (p = not significant). Higher drug doses may result in additional decreases in plasma Abeta concentrations and a measurable decrease in CSF Abeta.