Donanemab in Early Symptomatic Alzheimer DiseaseThe TRAILBLAZER-ALZ 2 Randomized Clinical Trial

With your risk of dementia post stroke, what is your doctor's protocol to

objectively determine if  you have it? NOTHING LIKE USUAL?  Then you don't have a functioning stroke doctor.

RUN AWAY!

Your risk of dementia, has your doctor told you of this?  Your doctor is responsible for preventing this!

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

The latest here:

 

Donanemab in Early Symptomatic Alzheimer DiseaseThe TRAILBLAZER-ALZ 2 Randomized Clinical Trial

John R. Sims, MD¹; Jennifer A. Zimmer, MD¹; Cynthia D. Evans, PhD¹; et al Ming Lu, MD, MS, MPH¹; Paul Ardayfio, PhD¹; JonDavid Sparks, PhD¹; Alette M. Wessels, PhD¹; Sergey Shcherbinin, PhD¹; Hong Wang, PhD¹; Emel Serap Monkul Nery, MD¹; Emily C. Collins, PhD¹; Paul Solomon, PhD²; Stephen Salloway, MD^3,4; Liana G. Apostolova, MD⁵; Oskar Hansson, MD, PhD⁶; Craig Ritchie, MD, PhD⁷; Dawn A. Brooks, PhD¹; Mark Mintun, MD¹; Daniel M. Skovronsky, MD, PhD¹; for the TRAILBLAZER-ALZ 2 Investigators

Author Affiliations Article Information

JAMA. Published online July 17, 2023. doi:10.1001/jama.2023.13239

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Abstract

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Editorial

Comment

• Editorial
  Donanemab for Alzheimer Disease—Who Benefits and Who Is Harmed?
  Jennifer J. Manly, PhD; Kacie D. Deters, PhD
• Editorial
  Amyloid-Targeting Monoclonal Antibodies for Alzheimer Disease
  Gil D. Rabinovici, MD; Renaud La Joie, PhD
• Editorial
  Novel Alzheimer Disease Treatments and Reconsideration of US Pharmaceutical Reimbursement Policy
  Meredith B. Rosenthal, PhD
• Editorial
  Ushering in a New Era of Alzheimer Disease Therapy
  Eric W. Widera, MD; Sharon A. Brangman, MD; Nathaniel A. Chin, MD

Key Points

Question  Does donanemab, a monoclonal antibody designed to clear brain amyloid plaque, provide clinical benefit in early symptomatic Alzheimer disease?

Findings  In this randomized clinical trial that included 1736 participants with early symptomatic Alzheimer disease and amyloid and tau pathology, the least-squares mean change in the integrated Alzheimer Disease Rating Scale score (range, 0-144; lower score indicates greater impairment) at 76 weeks was −6.02 in the donanemab group and −9.27 in the placebo group for the low/medium tau population and −10.19 in the donanemab group and −13.11 in the placebo group in the combined study population, both of which were significant differences.

Meaning  Among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab treatment significantly slowed clinical progression at 76 weeks.

Abstract

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.

Trial Registration  ClinicalTrials.gov Identifier: NCT04437511