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Biomedical subjects

Lon S Schneider

Publications and source records attributed to Lon S Schneider.

At least 19 recordsLinked to original sources
PubMed2025

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment.

INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

Humans↗
PubMed2006

Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease.

BACKGROUND: Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease. METHODS: In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks. RESULTS: There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22). CONCLUSIONS: Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00015548 [ClinicalTrials.gov].).

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PubMed2006

Risperidone in the treatment of psychosis of Alzheimer disease: results from a prospective clinical trial.

OBJECTIVE: The objective of this study was to evaluate efficacy and safety of low-dose risperidone for treating psychosis of Alzheimer disease (AD). METHOD: The authors conducted a randomized, eight-week, double-blind, placebo-controlled, multicenter trial involving nursing home residents diagnosed with AD and psychosis. Four hundred seventy-three patients were randomly assigned to placebo (N = 238) or 1.0 to 1.5 mg risperidone per day (N = 235). Coprimary efficacy end points were: changes in scores on the Behavioral pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression of Change (CGI-C). Protocol-specified subgroup analyses were performed by demographics and dementia severity. RESULTS: Efficacy analysis included 416 patients. Both groups improved significantly on the BEHAVE-AD Psychosis subscale and CGI-C with no significant difference between groups. In the subgroups analyses, a statistically significant treatment by Mini-Mental Status Examination (MMSE) interaction on the CGI-C (F([2,381]) = 3.90, p = 0.021) was observed with patients with more severe dementia (MMSE <10) showing significant differences at end point favoring risperidone treatment (chi(2) ([1]) = 5.11, p = 0.024). Mean risperidone dose was 1.03 +/- 0.24 mg per day. All-cause discontinuation rates were 25% for both risperidone and placebo. Treatment-emergent adverse events occurred in 74% risperidone versus 64% placebo patients, with somnolence occurring significantly more frequently with risperidone (16.2% versus 4.6%). Nine (3.8%) risperidone- and six (2.5%) placebo patients died during or within 30 days after treatment. CONCLUSION: This trial did not confirm earlier findings in this population.

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PubMed2006

Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials.

OBJECTIVE: Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease (AD) and other dementia. Several clinical trials have not shown efficacy, and there have been concerns about adverse events. The objective of this study was to assess the evidence for efficacy and adverse events of atypicals for people with dementia. METHODS: MEDLINE, the Cochrane Register of Controlled Trials, meetings, presentations, and information obtained from sponsors were used in this study. Published and unpublished randomized, placebo-controlled, double-blind, parallel-group trials in patients with AD or dementia of atypical antipsychotics marketed in the United States were studied. Clinical and trials characteristics, outcomes, and adverse events were extracted. Data were checked by a second reviewer. Fifteen trials including 16 contrasts of atypical antipsychotics with placebo met selection criteria: aripiprazole (k = 3), olanzapine (k = 5), quetiapine (k = 3), and risperidone (k = 5). A total of 3,353 patients were randomized to drug and 1,757 to placebo. Standard meta-analysis methods were used to summarize outcomes. RESULTS: Quality of the reporting of trials varied. Efficacy on rating scales was observed by meta-analysis for aripiprazole and risperidone, but not for olanzapine. Response rates were frequently not reported. There were smaller effects for less severe dementia, outpatients, and patients selected for psychosis. Approximately one-third dropped out without overall differences between drug and placebo. Adverse events were mainly somnolence and urinary tract infection or incontinence across drugs, and extrapyramidal symptoms or abnormal gait with risperidone or olanzapine. Cognitive test scores worsened with drugs. There was no evidence for increased injury, falls, or syncope. There was a significant risk for cerebrovascular events, especially with risperidone; increased risk for death overall was reported elsewhere. CONCLUSIONS: Small statistical effect sizes on symptom rating scales support the evidence for the efficacy of aripiprazole and risperidone. Incomplete reporting restricts estimates of response rates and clinical significance. Dropouts and adverse events further limit effectiveness. Atypicals should be considered within the context of medical need and the efficacy and safety of alternatives. Individual patient meta-analyses are needed to better assess clinical significance and effectiveness.

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PubMed2006

Design of Depression in Alzheimer's Disease Study-2.

OBJECTIVE: Research on the efficacy of antidepressant therapy for depressive symptoms in Alzheimer disease has been hampered by lack of systematic diagnosis, small sample sizes, and short-term follow up. To address these issues, the authors present the design of the Depression in Alzheimer's Disease Study-2 (DIADS-2), a randomized, placebo-controlled multicenter trial to evaluate the efficacy and safety of the selective serotonin reuptake inhibitor sertraline for the treatment of depression in people with Alzheimer disease. METHODS: The authors present and discuss the following important aspects of the design: the inclusion of structured psychosocial therapy for the caregivers of all participants; the measurement not only of patient mood outcomes, but also of global and functional outcomes for patients and mood and burden outcomes for caregivers; the ongoing rating of multiple diagnostic criteria to allow nosologic study of depression in Alzheimer disease; the evaluation of both short-term efficacy and longer-term outcomes; the follow up of all patients regardless of whether they complete study treatment; and the unmasking of treatment assignment at the conclusion of each patient's treatment phase. CONCLUSIONS: The authors believe these design elements are important features to be included in trials of depression and other neuropsychiatric disturbances in Alzheimer disease.

Affect↗
PubMed2005

Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials.

CONTEXT: Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease and other dementia; however, concerns have arisen about the increased risk for cerebrovascular adverse events, rapid cognitive decline, and mortality with their use. OBJECTIVE: To assess the evidence for increased mortality from atypical antipsychotic drug treatment for people with dementia. DATA SOURCES: MEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register (2005, Issue 1), meetings presentations (1997-2004), and information from the sponsors were searched using the terms for atypical antipsychotic drugs (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial. STUDY SELECTION: Published and unpublished randomized placebo-controlled, parallel-group clinical trials of atypical antipsychotic drugs marketed in the United States to treat patients with Alzheimer disease or dementia were selected by consensus of the authors. DATA EXTRACTION: Trials, baseline characteristics, outcomes, all-cause dropouts, and deaths were extracted by one reviewer; treatment exposure was obtained or estimated. Data were checked by a second reviewer. DATA SYNTHESIS: Fifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis. CONCLUSIONS: Atypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.

Antipsychotic Agents↗
PubMed2005

Clinical application of operationalized criteria for 'Depression of Alzheimer's Disease'.

OBJECTIVES: 'Depression of Alzheimer's Disease' (dAD) is a common complication of Alzheimer's disease and is increasingly recognized as a syndrome with a clinical presentation differing from major depression. Criteria for the diagnosis of dAD have been proposed previously. METHODS: This paper presents these criteria in operationalized format designed to be accessible for clinical use. Four cases are discussed that demonstrate the use of these criteria and illustrate important differences between dAD and major depression. RESULTS: The dAD criteria are broader than DSM-IV criteria for Major Depressive Episode and incorporate caregiver input. CONCLUSIONS: Given the differences between dAD and major depression diagnoses, it is important to assess the efficacy of treatments for dAD. Depression in Alzheimer's Disease-2 (DIADS-2) is a controlled trial of dAD treatments that will also assess the validity of these criteria.

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PubMed2005

Symptoms of late-life depression: frequency and change during treatment.

OBJECTIVE: The authors determined the symptoms frequently present in older patients with major depression that showed the greatest change during treatment and that best correlated with an independent measure of improvement (the Clinical Global Impression scale [CGI]). METHODS: Subjects included 728 patients over the age of 60 years with major depression who were selected for entry into a clinical trial. Authors determined the frequency of symptoms on the 17-item Hamilton Rating Scale for Depression (Ham-D) and the effect size of symptom change during treatment. RESULTS: Nine symptoms were identified that were frequent, showed the greatest change during treatment, and best correlated with CGI. The items included depressed mood; loss of interest in work and activities; psychic anxiety; somatic symptoms, general (decreased energy); somatic anxiety; guilt; middle insomnia; late insomnia; and suicidal ideation. These nine items accounted for 92% of the variance in the 17-item Ham-D score, correlated with the CGI at a level similar to the 17-item Ham-D, and were at least as sensitive as the 17-item Ham-D for detecting drug-placebo differences. A comparison with five other similar approaches in non-geriatric samples suggested that the symptoms identified were relatively similar in both age-groups. CONCLUSIONS: Symptoms frequent in patients with late-life depression are similar to those in mixed-aged samples. Nine of the Ham-D items appear most useful for assessment of change during treatment.

Age of Onset↗
PubMed2005

A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer's type.

CONTEXT: Previous studies of Ginkgo biloba extract (GbE) in patients with various forms of cognitive impairment or dementia have shown promising results. OBJECTIVE: To determine the clinical efficacy of GbE in mild to moderate dementia of the Alzheimer type. DESIGN: Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial. SETTING: Outpatient clinics of universities and private research centers specialized in dementia. PATIENTS: 513 outpatients with uncomplicated dementia of the Alzheimer's type scoring 10 to 24 on the Mini-Mental State Examination and less than 4 on the modified Hachinski Ischemic Score, free of other serious illnesses and not requiring continuous treatment with any psychoactive drug. INTERVENTION: 26-week treatment with GbE at daily doses of 120 mg or 240 mg or placebo. MAIN OUTCOMES: Cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC). RESULTS: There were no significant between-group differences for the whole sample. There was little cognitive and functional decline of the placebo-treated patients, however. For a subgroup of patients with neuropsychiatric symptoms there was a greater decline of placebo-treated patients and significantly better cognitive performance and global assessment scores for the patients on GbE. CONCLUSION: The trial did not show efficacy of GbE, however, the lack of decline of the placebo patients may have compromised the sensitivity of the trial to detect a treatment effect. Thus, the study remains inconclusive with respect to the efficacy of GbE.

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PubMed2004

Psychosis of Alzheimer's disease: clinical characteristics and history.

The concept of psychosis of Alzheimer's disease and dementia is developed with respect to prevalence, incidence, clinical characteristics, clinical course, and potential response to treatment. Psychosis frequently occurs subsequent to the onset of dementia. Published prevalence estimates of psychosis in patients with AD range from 10 to 73% with an overall median of 34% within clinic populations, and from 7 to 20% in community and clinical trials populations depending on definitions used. Among people with AD who have no psychotic symptoms there appears to be an annualized incidence of psychosis of about 20% in outpatients, and a much higher rate in nursing home patients. Female gender, somewhat greater cognitive impairment among outpatients, somewhat lesser cognitive impairment among nursing home patients, and physical aggression are more associated with psychotic signs and symptoms than not. Right frontal hypometabolism and greater frontal neuropsychological deficits occur in AD patients with psychosis in comparison to those without. Among nursing home patients with dementia who have clinically significant agitation, the substantial majority have delusions or hallucinations. Among patients in nursing homes with dementia and psychosis, nearly two-thirds have persistent symptoms over at least 12 weeks, and among outpatient studies, hallucinations and delusions may persist in approximately 40-50% over periods of 3 months to one year. There is some evidence that psychotic symptoms improve modestly with antipsychotic medication treatment. There is sufficient descriptive and empirical research to support the validity of a syndrome of psychosis of Alzheimer's disease.

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