More Evidence Lowering Amyloid Is Clinically Beneficial in Early Alzheimer’s

 Is your competent? doctor ready with EXACT DEMANTIA PREVENTION PROTOCOLS?  

With your extra risk of dementia post stroke; DOES YOUR DOCTOR HAVE EXACT DEMENTIA PREVENTION PROTOCOLS? NO? So, your doctor is incompetent? 

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 

Alzheimer's Blood Test Cleared for Primary Care Use

Has your competent? doctor explained problems encountered with donanemab? No knowledge is grounds for firing!

donanemab (5 posts to January 2021)

The latest here:

More Evidence Lowering Amyloid Is Clinically Beneficial in Early Alzheimer’s

Reduced amyloid burden after treatment with the antiamyloid donanemab (Kisunla, Eli Lilly) correlated strongly with slower cognitive and functional decline in adults with early symptomatic Alzheimer’s disease (AD) in a secondary analysis of the phase 3 TRAILBLAZER-ALZ 2 trial.

The TRAILBLAZER-ALZ 2 study showed that donanemab effectively removed beta-amyloid plaques from the brain and demonstrated statistically significant slowing of cognitive and functional decline compared with placebo.

“This secondary analysis assessed the correlation between these two endpoints and showed that lower brain amyloid levels after treatment were directly associated with greater slowing of cognitive and functional decline,” Ming Lu, MD, associate vice president, Statistics, Eli Lilly and Company, and author on the secondary analysis, told Medscape Medical News. 

“These results support the growing body of knowledge that targeting beta-amyloid in the brain is a valid therapeutic approach and that patients may benefit from reducing beta-amyloid burden,” Lu said. 

The study was published online on October 13 in JAMA Neurology.

Lower Amyloid, Slower Decline

Results from the TRAILBLAZER-ALZ 2 trial showed treatment with donanemab significantly reduced amyloid plaque by 87 centiloids (CL) over 76 weeks and slowed clinical progression by 22% and 29% compared with placebo, as assessed by integrated AD Rating Scale (iADRS) and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) scores, respectively.

These results led to approval of donanemab for early symptomatic AD in July 2024.

Yet, the relationship between amyloid removal and clinical benefit has remained uncertain, with mixed results across studies of similar drugs such as aducanumab and lecanemab.

To investigate, Lu and colleagues analyzed 1582 participants (mean age, 73 years) from TRAILBLAZER-ALZ 2 with confirmed amyloid and tau pathology; 766 were treated with donanemab (every 4 weeks for up to 72 weeks, with outcomes assessed through 76 weeks), and 816 were given placebo.

They categorized participants into one of 10 groups (deciles) based on their lowest amyloid value observed after treatment. Cognitive decline was assessed using iADRS and CDR-SB scores over 76 weeks, and measured plasma biomarkers included phosphorylated tau (p-tau217 and p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL).

Correlations between median amyloid levels and biomarker or clinical changes were calculated using mixed models for repeated measures.

At baseline, mean amyloid values were 143.4 CL in the highest decile and 87.5 CL in the lowest decile compared with the overall trial mean of 102.9 CL. 

Across the trial population, lower posttreatment amyloid levels were correlated with slower clinical progression as measured by iADRS score (coefficient of determination [R²], 0.73) and CDR-SB score (R², 0.87) and with decreased p-tau217 (R², 0.86), p-tau181 (R², 0.88), and GFAP (R², 0.87) scores but not NfL scores (R², 0.03).

Notably, nearly all (99.6%) participants in the lowest three deciles of amyloid posttreatment received donanemab, and all (100%) donanemab-treated participants in the lowest three deciles achieved amyloid clearance (< 24.1 CL) by 76 weeks.

Participants in the lowest deciles of amyloid had the least cognitive decline, whereas those with higher posttreatment amyloid (mostly on placebo) worsened more rapidly. Patients who achieved amyloid clearance experienced the slowest disease progression.

‘Major’ Clinical Implications

“This is the first published analysis within one antiamyloid agent, as opposed to comparisons across drugs, that clearly shows that full clearance with treatment increases the likelihood of a clinical benefit,” study investigator David Knopman, MD, professor of neurology at the Mayo Clinic in Rochester, Minnesota, told Medscape Medical News. 

“This has major implications for understanding how the drugs work but also practically speaks to the value, or lack thereof, in continuing treatment beyond 18 months in a patient who failed to fully clear amyloid by 18 months,” Knopman said.

Commenting on the findings Rebecca M. Edelmayer, PhD, vice president of scientific engagement at the Alzheimer’s Association, said researchers have long known beta-amyloid buildup is key to Alzheimer’s progression. “This article reinforces that it also is an important, viable, and useful treatment target in people with early symptomatic Alzheimer’s,” she told Medscape Medical News, adding that major plaque reductions correlate with the best outcomes.

Edelmayer added that the analysis also “further reinforces the need for and benefits of early and accurate diagnosis and early intervention in order to get the greatest possible treatment effect.”

“In the real world, most people with dementia — regardless of diagnosis — have brain changes characteristic of more than one disease/dementia, including Alzheimer’s disease, vascular dementia, dementia with Lewy bodies, and others. This is known as mixed dementia. This reality reinforces the need to develop treatment strategies that address Alzheimer’s and other dementias in multiple ways, from multiple angles,” Edelmayer noted.

She added that the Alzheimer’s Association is committed to advancing all potential treatment avenues and exploring methods for combining diverse approaches into combination therapies. 

“For example, the Alzheimer’s Association’s Part the Cloud initiative has raised nearly $90 million and funded 72 clinical trials across the globe focusing on a wide range of new and innovative treatment targets,” Edelmayer added.

Funding for this research was provided by Eli Lilly and Company. Lu and eight co-authors declared having relationships with the company. Knopman and Edelmayer reported having no disclosures.