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Biomedical subjects

S Gracon

Publications and source records attributed to S Gracon.

9 recordsLinked to original sources
PubMed2003

MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD.

OBJECTIVE: To assess the feasibility of using MRI measurements as a surrogate endpoint for disease progression in a therapeutic trial for AD. METHODS: A total of 362 patients with probable AD from 38 different centers participated in the MRI portion of a 52-week randomized placebo-controlled trial of milameline, a muscarinic receptor agonist. The therapeutic trial itself was not completed due to projected lack of efficacy on interim analysis; however, the MRI arm of the study was continued. Of the 362 subjects who underwent a baseline MRI study, 192 subjects underwent a second MRI 1 year later. Hippocampal volume and temporal horn volume were measured from the MRI scans. RESULTS: The annualized percent changes in hippocampal volume (-4.9%) and temporal horn volume (16.1%) in the study patients were consistent with data from prior single-site studies. Correlations between the rate of MRI volumetric change and change in behavioral/cognitive measures were greater for the temporal horn than for the hippocampus. Decline over time was more consistently seen with imaging measures, 99% of the time for the hippocampus, than behavioral/cognitive measures (p < 0.001). Greater consistency in MRI than behavioral/clinical measures resulted in markedly lower estimated sample size requirements for clinical trials. The estimated number of subjects per arm required to detect a 50% reduction in the rate of decline over 1 year are: AD Assessment Scale-cognitive subscale 320; Mini-Mental Status Examination 241; hippocampal volume 21; temporal horn volume 54. CONCLUSION: The consistency of MRI measurements obtained across sites, and the consistency between the multisite milameline data and that obtained in prior single-site studies, demonstrate the technical feasibility of using structural MRI measures as a surrogate endpoint of disease progression in therapeutic trials. However, validation of imaging as a biomarker of therapeutic efficacy in AD awaits a positive trial.

Adolescent↗
PubMed1997

[Advantages in long-term treatment with Cognex in Alzheimer disease].

Early diagnosis and treatment of AD is critical to maximize benefits for the patient and the caregiver. It is important to intervene early in the illness, before the quality of life of the patient and the caregiver has deteriorated to the point where treatment only prolongs an already difficult situation. If treatment begins early enough in the disease course, loss of functional independence may be delayed, just as nursing home placement was delayed in this study. In this way, quality of life is improved for both the patient and the caregiver.

Activities of Daily Living↗
PubMed1996

The use of survival analysis techniques in evaluating the effect of long-term tacrine (Cognex) treatment on nursing home placement and mortality in patients with Alzheimer's disease.

Survival analysis techniques using Cox proportional hazards regressions with time-dependent covariates, life table survival plots, and Kaplan-Meier estimates were used to evaluate the effect of long-term tacrine hydrochloride (Cognex) treatment on nursing home placement (NHP) and mortality in patients with Alzheimer's disease. Patients with probable Alzheimer's disease (NINCDS criteria) who were randomized in a 30-week double-blind, placebo-controlled, parallel-group, high-dose study of tacrine (1) were subsequently allowed to receive long-term, open-label treatment during which they could receive doses up to 160 mg/day. Using last tacrine dose, the analyses demonstrated a dose-response relationship where patients on higher tacrine doses were less likely to enter a nursing home or die than patients on lower doses. The Cox proportional hazards regression approach with time-dependent covariates is also compared to logistic regression, which looks only at the crude proportions of patients having the event. Since logistic regression does not allow for the use of time-dependent covariates, it provides somewhat less conservative estimates of the magnitude of the treatment effect.

Alzheimer Disease↗
PubMed1996

Long-term tacrine (Cognex) treatment: effects on nursing home placement and mortality, Tacrine Study Group.

OBJECTIVE: To assess the possible association between tacrine (Cognex, manufactured by Parke-Davis, Morris Plains, NJ) dose and likelihood of nursing home placement (NHP) or death in patients with AD. DESIGN: A 30-week, randomized, double-blind, placebo-controlled, parallel-group multicenter clinical trial involving 663 patients, after which patients were treated openly and followed up a minimum of 2 years later. PATIENTS: At baseline, outpatients were at least 50 years of age, met criteria for probable AD, with baseline Mini-Mental State Examination scores between 10 and 26 (inclusive), were otherwise healthy, and had a caregiver who could provide assessments and ensure medication compliance. INTERVENTIONS: mandomized assignment to placebo or one of three ascending dosage regimens of tacrine over 30 weeks, followed by open label treatment for all patients who began the double-blind trial. OUTCOME MEASURES: NHP and death were examined using logistic regression. RESULTS: PATIENTS who remained on tacrine and were receiving doses > 80 mg/d or > 120 mg/d were less likely to have entered a nursing home than patients on lower doses (odds ratios > 2.7,2.8, respectively.) There was a trend for lower mortality for patients receiving > 120 mg/d (p = 0.063). CONCLUSIONS: Treatment with tacrine at doses > 80 mg/d was associated with a reduced likelihood of NHP. These data demonstrate that tacrine's 30-week effects on cognitive function and clinicians' global ratings may generalize to effects on a major milestone of AD. Future studies should attempt to replicate these findings prospectively.

Aged↗
PubMed1994

Observations on the short-term 'natural history' of probable Alzheimer's disease in a controlled clinical trial.

We examined the performance of patients with probable Alzheimer's disease (AD) who participated in the placebo arm of a 12-week clinical trial. Assessments occurred at baseline and at 4, 6, 10, and 12 weeks after starting study medication. Patients received the Alzheimer's Disease Assessment Scale--Cognitive on all five occasions and the Mini-Mental State Examination on three occasions (baseline, week 6, and week 12). Their primary caregivers completed the Progressive Deterioration Scale on all five visits. This self-administered questionnaire consists of 29 items regarding the patient's behavioral and functional status. The extrapolated yearly rate of change of the mental status examinations was considerably smaller than expected compared with uncontrolled natural history studies. In addition, there was a large within-subject variability on all three measures. Scores from the baseline assessments contributed more to the variability than did the later assessments. The small magnitude of change, as well as the large between-subjects and within-subject variability, points out the methodologic drawbacks of short-duration therapeutic trials in patients with AD and the challenges in demonstrating reliable treatment effects for potential therapeutic agents.

Aged↗