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P Tariot

Publications and source records attributed to P Tariot.

14 recordsLinked to original sources
PubMed2006

Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease.

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.

Alanine↗
PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗
PubMed2001

Pharmacotherapy of Alzheimer's disease: is there a need to redefine treatment success?

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.

Activities of Daily Living↗
PubMed2001

Current status and new developments with galantamine in the treatment of Alzheimer's disease.

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.

Aged↗
PubMed2000

Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.

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.

Aged↗
PubMed1997

Treatment of agitation in dementia.

Agitation occurs commonly in patients with dementia. Before symptomatic pharmacotherapy is undertaken, it is imperative to perform a sequence of evaluations and interventions to establish whether simpler and safer, nonpharmacologic approaches will be beneficial. When psychotropic medications are used they should be used judiciously, in the lowest effective doses and for the shortest period of time necessary. Ineffective medications should be stopped, and even effective medications should be empirically tapered in most patients to learn whether treatment is still necessary. Antipsychotics probably show the greatest benefit for agitation associated with psychotic features; they have less demonstrated efficacy for agitation not associated with psychotic features. The side effects of typical agents are legion; data are pending regarding atypical agents. The available evidence regarding nonneuroleptic medications ranges from case reports to well-designed, double-blind, placebo-controlled, randomized, parallel group studies. Literature exists describing the use of anticonvulsants, anxiolytics, serotonergic antidepressants, and other agents to manage agitation. Carbamazepine and divalproex sodium (valproate) have demonstrated efficacy in uncontrolled studies, whereas the use of carbamazepine has produced negative results in one small controlled study and positive results in two larger controlled studies. Buspirone has shown benefit in some open trials. Encouraging early findings have been reported for trazodone, including from one controlled trial. Varying results have been obtained using selective serotonin reuptake inhibitors, but with consistently encouraging anecdotes. In the aggregate, the evidence suggests but does not prove that alternatives to traditional antipsychotics exist. Again, none of these agents has yet been approved for this purpose by the FDA. As more studies become available we will have a better idea about which classes of agents are most efficacious. It is likely that there may be a role for "rational" polypharmacy in the management of this distressing complication of dementia. However, no studies that we know of address combination therapy, so the clinician must contemplate this option on a case-by-case basis. Clinical trials data are pending from studies with divalproex sodium, carbamazepine, haloperidol versus trazodone versus placebo, risperidone, olanzapine, quetiapine, donepezil, xanomeline, tacrine, buspirone, and sertraline, at the very least. These data will undoubtedly have a major impact on how we care for our patients and lead to revisions of current practice guidelines.

Aged↗
PubMed1997

A longitudinal study of behavioral pathology across five levels of dementia severity in Alzheimer's disease: the CERAD Behavior Rating Scale for Dementia. The Alzheimer's Disease Cooperative Study.

As part of the Alzheimer's Disease Cooperative Study (ADCS) Instrument Development Project, the CERAD Behavior Rating Scale for Dementia (BRSD) was examined for its sensitivity to degree of cognitive impairment, its test-retest reliability, and its sensitivity to longitudinal change. Sixty-four normal elderly participants and 261 patients with AD stratified into severity groups based on Mini-Mental State Exam (MMSE) scores were rated on the BRSD at baseline and 12-month follow-up visits. A subset of subjects was evaluated at a 1-month follow-up visit. Baseline BRSD Total Score discriminated the normal group from each AD group, and mean Total Score significantly increased with increasing dementia severity. Test-retest reliability between baseline and 1-month Total Scores was satisfactory for all AD groups. Longitudinal change was evaluated by 12-month change scores, which were significant in only the normal and in one AD group. From the results, we argue that the value of behavioral pathology assessment in clinical trials would be enhanced if additive scores were based on groups of correlated items rather than on a broad array of behaviors, some of which may increase and others may decrease in frequency as AD progresses.

Aged↗
PubMed1996

Minimum Data Set Plus (MDS+) scores compared with scores from five rating scales.

OBJECTIVE: To compare mandated Minimum Data Set Plus (MDS+) ratings of behavior, function, mood, communication, and cognition to ratings of these domains using analogous research instruments. DESIGN: Cross-sectional correlational study of criterion-related validity. SETTING: Three nursing homes in Rochester, New York. PARTICIPANTS: Fifty-two nursing home residents. MEASUREMENTS: Nursing home staff completed the MDS+ for each subject. Research scales were completed by trained research clinicians, independently of and blinded to the MDS+ results, using the Mini-Mental State Exam (MMSE), Brief Psychiatric Rating Scale (BPRS), Dementia Mood Assessment Scale (DMAS), Psychogeriatric Dependency Rating Scale (PGDRS), and Physical Signs and Symptoms Scale (PSMS). RESULTS: MDS+ measures of functional status, cognitive impairment, and communication were highly correlated with comparable research rating scale scores. Pearson correlation between MDS-functional status and PSMS scores was 0.89, between MDS-dementia and BPRS Factor 3 (representing cognitive dysfunction) and MMSE scores was 0.85 and 0.77, respectively, and between MDS-communication and MMSE and PGDRS Item 6 (assessing communication) scores was 0.74 and 0.62, respectively. Behavior and mood scores did not correlate nearly as well with comparable research scale scores. Pearson correlation between MDS- behavior and PGDRS and BPRS total scores was 0.54 and 0.51, respectively , and between MDS-mood and BPRS Factor 1 (depression) and DMAS 1-17 subtotal (mood disturbance) scores was 0.20 and 0.20, respectively. CONCLUSION: This preliminary study in a small sample shows marked agreement between three of the five MDS+ components analyzed and comparable research rating scales and confirms that behavior and mood are difficult to assess with simple instruments.

Activities of Daily Living↗
PubMed1996

Measures of psychiatric symptoms in Alzheimer patients: a review.

This review of instruments for the identification and quantification of psychiatric symptoms in Alzheimer disease (AD) is intended as a reference source for clinicians and researchers concerned with evaluating, quantifying, and managing psychiatric symptoms in AD. We review 16 clinician- and caregiver-rated scales selected from >30 scales on the basis of their face validity, their psychometric properties, the frequency of their use, and their promise as assessment instruments. Instruments are described in terms of the population on which they were developed, the symptoms assessed, informant, by whom administered, time to administer, time interval covered, number of items, measurement of frequency and severity, assessment of impact on caregiver, reliability, validity, and scoring. Recommendations are made concerning the best use of each scale. We summarize in table form the sources of information for instruments, characteristics of the instruments by domain, and potential use of instruments for quantification or management of symptoms and for estimation of caregiver burden. There are a number of reliable and valid scales for the assessment of psychiatric symptoms in AD, each with specific assets and liabilities. Knowledge of the specifics of these scales will enable clinicians and researchers to select the best instruments for their particular needs and to design more effective instruments.

Activities of Daily Living↗
PubMed1989

Carbamazepine-induced tics.

Although a variety of dyskinesias are known to develop during anticonvulsant therapy, carbamazepine-induced tics are rarely recognized. We report three patients with an underlying movement disorder (Huntington's disease, tardive dyskinesia, and Tourette's syndrome) who experienced the onset or exacerbation of tics after the introduction of carbamazepine. These cases confirm the phenomenon of carbamazepine-induced tics and suggest that basal ganglia neuropathology may be an important predisposing factor. The dopaminergic effects of carbamazepine may be responsible for the induction of tics.

Adolescent↗
PubMed1987

Function of the adrenal cortex in patients with major depression.

Failure to suppress cortisol secretion after administration of dexamethasone occurs in up to 50% of depressed patients. To test whether this hypothalamic-pituitary-adrenal (HPA) overactivity is associated with adrenocortical hyperresponsiveness, we performed dexamethasone suppression tests (DSTs) and adrenocorticotropic hormone (ACTH) stimulation tests in depressed subjects and subjects with other psychiatric disorders. Three groups were defined: depressed nonsuppressors, depressed suppressors, and other suppressors. While predexamethasone and postdexamethasone cortisol concentrations were greater in the depressed nonsuppressor group, ACTH concentrations did not differ among groups. After receiving alpha-ACTH[1-24] (4.2 micrograms/kg), depressed nonsuppressors had greater increases in stimulated cortisol secretion than the other groups. These results demonstrate that in a subgroup of depressed patients, HPA overactivity is associated with adrenocortical hyperresponsiveness.

Adrenal Cortex↗
PubMed1985

Scopolamine challenges in Alzheimer's disease.

A challenge paradigm was designed to test the functional sensitivity to anticholinergic agents in Alzheimer's disease. Ten patients with dementia of the Alzheimer type were serially administered three different intravenous doses of the centrally active anticholinergic drug scopolamine and placebo. Testing was carried out in a placebo-controlled, double-blind fashion to measure cognitive, physiologic and behavioral changes. Alzheimer patients showed a marked, dose-related behavioral and cognitive sensitivity to temporary cholinergic blockade. Scopolamine testing may serve as an index of the status of central cholinergic functional integrity, and ultimately may prove useful as a diagnostic or staging test in the evaluation of the cholinergic system in dementia. Research is currently under way with elderly age-matched controls and populations with other neuropsychiatric disorders to explore this hypothesis further.

Adult↗