Long-term safety of gantenerumab in participants with Alzheimer's disease: A phase III, open-label extension study (SCarlet RoAD).

Background: Gantenerumab is a fully human anti-amyloid-β (Aβ) immunoglobulin G1 monoclonal antibody for subcutaneous (SC) administration. The efficacy and safety of low-dose (105 mg or 225 mg) gantenerumab were investigated in SCarlet RoAD (SR; NCT01224106), a Phase III, double-blind (DB), placebo-controlled study in participants with prodromal Alzheimer's disease. Following a pre-planned futility analysis, SR was converted into an open-label extension (OLE) study.

Promoting diversity in clinical trials: insights from planning the ALUMNI AD study in historically underrepresented US populations with early symptomatic Alzheimer's disease.

Unlabelled: Clinical trial participation across disease areas, including Alzheimer's disease (AD), has been biased towards White participants of European ancestry. To support clinical decision-making across diverse populations, we must recognize and address barriers to trial participation. To inform the design of ALUMNI AD, a trial focused on historically underrepresented AD populations, we held advice-seeking fora with key stakeholders to understand barriers and identify potential solutions to maximize trial participation of underrepresented racial and ethnic groups in the US.

Long-Term Safety of Gantenerumab in Participants with Alzheimer's Disease: A Phase III, Double-Blind, and Open-Label Extension Study (Marguerite RoAD).

Background: Gantenerumab is an anti-amyloid-β immunoglobulin G1 monoclonal antibody for subcutaneous (SC) administration. The efficacy and safety of low-dose (105 mg or 225 mg) gantenerumab were investigated in Marguerite RoAD (MR; NCT02051608), a Phase III, double-blind (DB), placebo-controlled study in participants with mild Alzheimer's disease (AD) dementia. Following a preplanned futility analysis of the SCarlet RoAD study (NCT01224106), MR was converted into an open-label extension (OLE).

Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials.

Importance: Alzheimer disease (AD), a neurodegenerative disease characterized by β-amyloid plaques and τ tangles in the brain, represents an unmet medical need with no fully approved therapeutics to modify disease progression.

Objective: To investigate the safety and efficacy of crenezumab, a humanized monoclonal immunoglobulin G4 antibody targeting β-amyloid oligomers, in participants with prodromal to mild (early) AD.

Design, Setting, And Participants: Two phase 3 multicenter randomized double-blind placebo-controlled parallel-group efficacy and safety studies of crenezumab in participants with early AD, CREAD and CREAD2, were initiated in 2016 and 2017, respectively, and were designed to evaluate the efficacy and safety of crenezumab in participants with early AD.

A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years.

Statistical Model of Dynamic Markers of the Alzheimer's Pathological Cascade.

Objectives: Alzheimer's disease (AD) is a progressive disease reflected in markers across assessment modalities, including neuroimaging, cognitive testing, and evaluation of adaptive function. Identifying a single continuum of decline across assessment modalities in a single sample is statistically challenging because of the multivariate nature of the data. To address this challenge, we implemented advanced statistical analyses designed specifically to model complex data across a single continuum.

Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD).

Background: Sembragiline is a potent, selective, long-acting, and reversible MAO-B inhibitor developed as a potential treatment for Alzheimer's disease (AD).

Objective: To evaluate the safety, tolerability, and efficacy of sembragiline in patients with moderate AD.

Methods: In this Phase II study (NCT01677754), 542 patients with moderate dementia (MMSE 13-20) on background acetylcholinesterase inhibitors with/without memantine were randomized (1:1:1) to sembragiline 1 mg, 5 mg, or placebo once daily orally for 52 weeks.

Prediction of Conversion to Alzheimer's Disease with Longitudinal Measures and Time-To-Event Data.

Background: Identifying predictors of conversion to Alzheimer's disease (AD) is critically important for AD prevention and targeted treatment.

Objective: To compare various clinical and biomarker trajectories for tracking progression and predicting conversion from amnestic mild cognitive impairment to probable AD.

Methods: Participants were from the ADNI-1 study.

Validation of olfactory deficit as a biomarker of Alzheimer disease.

Background: We evaluated smell identification as a biomarker for Alzheimer disease (AD) by assessing its utility in differentiating normal aging from an amnestic disorder and determining its predictive value for conversion from amnestic mild cognitive impairment (aMCI) to AD.

Methods: Cross-sectional study (AD = 262, aMCI = 110, controls = 194) measuring smell identification (University of Pennsylvania Smell Identification Test [UPSIT]) and cognitive status was performed, as well as longitudinal analysis of aMCI participants (n = 96) with at least 1 year follow-up (mean 477.6 ± 223.

Efficacy and Safety of Donepezil in Chinese Patients with Severe Alzheimer's Disease: A Randomized Controlled Trial.

Background: Donepezil has been used worldwide for the treatment of severe Alzheimer's disease (AD). Whether it is also appropriate for severe AD in Chinese patients remains unknown.

Objective: To determine whether donepezil is effective and tolerable for Chinese patients with severe AD.

PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury.

Background: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI).

Methods: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily.

Lipoprotein-associated phospholipase A2, homocysteine, and Alzheimer's disease.

Introduction: Lipoprotein-associated phospholipase A2 (Lp-PLA2) and homocysteine (Hcy) have been linked to inflammation and Alzheimer's disease (AD). Using a case-control design, we examined their independent effects and interactions with cardiovascular disease equivalent (CVDE), on AD risk.

Methods: AD cases and controls were from the Texas Alzheimer's Research and Care Consortium study.

Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials.

Introduction: Clinical and MRI measurements can track disease progression in PSP, but many have not been extensively evaluated in multicenter clinical trials. We identified optimal measures to capture clinical decline and predict disease progression in multicenter PSP trials.

Methods: Longitudinal clinical rating scales, neuropsychological test scores, and volumetric MRI data from an international, phase 2/3 clinical trial of davunetide for PSP (intent to treat population, n = 303) were used to identify measurements with largest effect size, strongest correlation with clinical change, and best ability to predict dropout or clinical decline over one year as measured by PSP Rating Scale (PSPRS).

Prevalence and correlates of cognitive asymmetry in a large sample of Alzheimer's disease patients.

Previous research has suggested that a significant minority of patients with Alzheimer's disease (AD) exhibit asymmetric cognitive profiles (greater verbal than visuospatial impairment or vice versa) and that these patient subgroups may differ in demographic and other characteristics. Prior studies have been relatively small, and this investigation sought to examine correlates of asymmetry in a large patient sample (N = 438). Patients were classified into the following cognitive profile groups: low verbal, symmetric, and low visuospatial.

How Do Scores on the ADAS-Cog, MMSE, and CDR-SOB Correspond?

Objective: Clinicians and researchers who measure cognitive dysfunction often use the Alzheimer's Disease Assessment Scale--Cognitive Subscale (ADAS-Cog), the Mini-Mental State Examination (MMSE), or the Clinical Dementia Rating scale (CDR-SOB). But, the use of different measures can make it difficult to compare data across patients or studies. What is needed is a simple chart that shows how scores on these three important measures correspond to each other.