Browsing by Author "Ritchie, Craig"

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    Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial
    (American Medical Association, 2023) Sims, John R.; Zimmer, Jennifer A.; Evans, Cynthia D.; Lu, Ming; Ardayfio, Paul; Sparks, JonDavid; Wessels, Alette M.; Shcherbinin, Sergey; Wang, Hong; Monkul Nery, Emel Serap; Collins, Emily C.; Solomon, Paul; Salloway, Stephen; Apostolova, Liana G.; Hansson, Oskar; Ritchie, Craig; Brooks, Dawn A.; Mintun, Mark; Skovronsky, Daniel M.; TRAILBLAZER-ALZ 2 Investigators; Neurology, School of Medicine
    Importance: There are limited efficacious treatments for Alzheimer disease. Objective: To assess efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque. Design, setting, and participants: Multicenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 (last patient visit for primary outcome in April 2023). Interventions: Participants were randomized in a 1:1 ratio to receive donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks for 72 weeks. Participants in the donanemab group were switched to receive placebo in a blinded manner if dose completion criteria were met. Main outcomes and measures: The primary outcome was change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks (range, 0-144; lower scores indicate greater impairment). There were 24 gated outcomes (primary, secondary, and exploratory), including the secondary outcome of change in the sum of boxes of the Clinical Dementia Rating Scale (CDR-SB) score (range, 0-18; higher scores indicate greater impairment). Statistical testing allocated α of .04 to testing low/medium tau population outcomes, with the remainder (.01) for combined population outcomes. Results: Among 1736 randomized participants (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] with low/medium tau pathology and 552 [31.8%] with high tau pathology), 1320 (76%) completed the trial. Of the 24 gated outcomes, 23 were statistically significant. The least-squares mean (LSM) change in iADRS score at 76 weeks was -6.02 (95% CI, -7.01 to -5.03) in the donanemab group and -9.27 (95% CI, -10.23 to -8.31) in the placebo group (difference, 3.25 [95% CI, 1.88-4.62]; P < .001) in the low/medium tau population and -10.2 (95% CI, -11.22 to -9.16) with donanemab and -13.1 (95% CI, -14.10 to -12.13) with placebo (difference, 2.92 [95% CI, 1.51-4.33]; P < .001) in the combined population. LSM change in CDR-SB score at 76 weeks was 1.20 (95% CI, 1.00-1.41) with donanemab and 1.88 (95% CI, 1.68-2.08) with placebo (difference, -0.67 [95% CI, -0.95 to -0.40]; P < .001) in the low/medium tau population and 1.72 (95% CI, 1.53-1.91) with donanemab and 2.42 (95% CI, 2.24-2.60) with placebo (difference, -0.7 [95% CI, -0.95 to -0.45]; P < .001) in the combined population. Amyloid-related imaging abnormalities of edema or effusion occurred in 205 participants (24.0%; 52 symptomatic) in the donanemab group and 18 (2.1%; 0 symptomatic during study) in the placebo group and infusion-related reactions occurred in 74 participants (8.7%) with donanemab and 4 (0.5%) with placebo. Three deaths in the donanemab group and 1 in the placebo group were considered treatment related. Conclusions and relevance: Among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population.
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    Implementing Digital Cognitive Assessments to Detect Cognitive Impairment: Results from the Davos Alzheimer’s Collaborative Early Detection Program
    (Wiley, 2025-01-09) MacLeod, Tim; Murray, James F.; dos Santos Filho, Otelo Corrêa; de Sá Paiva Lima, Marcilea Dias; Govia, Ishtar; Robinson, Janelle; Kowa, Hisatomo; Morimoto, Kohei; López-Ortega, Mariana; McKean, Alison; Ritchie, Craig; Baksh, Magda R.; Smith, Steven R.; Willis, Deanna R.; Brosch, Jared R.; Small, Seamus; Martin, Tammy; Selzler, Katherine J.; Medicine, School of Medicine
    Background: Cognitive impairment is frequently undetected or undiagnosed in the early stages. To increase the rates of detecting cognitive impairment, the Early Detection program of the Davos Alzheimer’s Collaborative System Preparedness (DAC‐SP) implemented digital cognitive assessments (DCA) in primary care and other non‐specialty settings. Methods: The DAC‐SP Early Detection program was initiated in 2021 in seven healthcare systems across six countries. Sites were able to choose from several DCAs, and clinicians were provided training, including recognizing signs and symptoms of cognitive decline, and provided with post‐diagnostic support. Patients were eligible for a DCA if they were over 60 years of age, able to hear and see well enough to complete the assessments, and had no prior diagnosis of dementia. The DCA tools included Linus Health’s Core Cognitive Evaluation, Cogstate Cognigram, and Cogstate Brief Battery. Results: The DCA results across the seven sites are presented in Table 1. There was notable variability in the number of patients screened across sites, which could be attributed to multiple factors (i.e., number of clinics onboarded/trained, additional testing for language and culture appropriateness of DCA tool prior to deployment, reduction in the number of elderly people visiting clinics during the COVID‐19 pandemic, available time of clinicians, etc.). The rate of cognitive impairment (abnormal and borderline) was also numerically higher at sites outside the US, independent of the DCA tool used. However, this study was not designed to evaluate operating characteristics of DCA tools, so further research is needed. Approximately 60% of the patients in the DAC‐SP Early Detection program tested abnormal or borderline for cognitive issues, suggesting the need for additional clinical assessment and follow‐up. Conclusion: Findings from the DAC‐SP Early Detection program demonstrated a DCA can be implemented in existing patient care workflows, including primary care settings, and across healthcare systems globally with different resource settings. Adoption of DCAs in clinical practice can help improve the ability to detect symptoms of cognitive impairment and provide much needed earlier screening and care for patients and their families.