Anti-amyloid antibody drugs and brain shrinkage

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BrianR
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Anti-amyloid antibody drugs and brain shrinkage

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Two very readable opinion pieces touching on evidence that anti-amyloid antibody treatments may exacerbate brain shrinkage. The summary is that this apparent phenomenon ought to be better understood before widespread use of these drugs (e.g. lecanemab).

Derek Lowe blog (motivated by the Stat article below): https://www.science.org/content/blog-post/brain-shrinkage-side-effect

Madhav Thambisetty in Stat: https://www.statnews.com/2022/11/28/anti-amyloid-drugs-treatment-associated-brain-shrinkage/
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TheresaB
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Re: Anti-amyloid antibody drugs and brain shrinkage

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BrianR wrote: Sun Dec 11, 2022 8:26 am Two very readable opinion pieces touching on evidence that anti-amyloid antibody treatments may exacerbate brain shrinkage. The summary is that this apparent phenomenon ought to be better understood before widespread use of these drugs (e.g. lecanemab).
I quoted one of those articles noting brain shrinkage in the Lecanamab: Efficacy, Side Effects, and More thread. This is concerning given that brain shrinkage is associated with dementia and we don't know long term effects of these drugs yet. l'll requote the four questions that the author had:
I propose four questions that should be pursued in the clinical trial data about lecanemab and other amyloid-targeting antibodies. These are:
• Does the loss of brain volume track with worsening cognitive performance or other side effects such as headache, confusion, and dizziness?
• Is there a relationship between brain volume loss and frequently observed amyloid-related imaging abnormalities (ARIA) that cause brain swelling or microbleeds in patients treated with these drugs?
• Is loss of brain volume related to higher levels of biomarkers of neurodegeneration?
• Are patients who show brain volume loss on MRI scans more likely to develop long-term worsening of cognitive decline?
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floramaria
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Re: Anti-amyloid antibody drugs and brain shrinkage

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In the absence of clear and compelling evidence that brain atrophy and ventricular expansion after exposure to anti-amyloid antibodies do not represent adverse treatment effects, existing data suggest cause for concern and uncertainty about the long-term effects of these changes.

As a physician who cares for people with Alzheimer’s and other dementias, I hope that these emerging anti-amyloid antibody therapies represent a significant advance in our ability to treat this devastating disease. But it is incumbent on drug developers and researchers to examine all the available data dispassionately and make rational, evidence-based decisions about the safety of these drugs.

Madhav Thambisetty is a neurologist and an adjunct professor of neurology at Johns Hopkins University School of Medicine. The views expressed here are his alone and do not necessarily reflect those of his employer or Johns Hopkins.
Among the negatives of the mabs, I’d not heard or read about Brain shrinkage before. Cause for concern indeed.
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BrianR
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Re: Anti-amyloid antibody drugs and brain shrinkage

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TheresaB wrote: Sun Dec 11, 2022 9:17 am I quoted one of those articles noting brain shrinkage in the Lecanamab: Efficacy, Side Effects, and More thread. This is concerning given that brain shrinkage is associated with dementia and we don't know long term effects of these drugs yet.
Thanks Theresa, I had forgotten that. Excellent questions that should be better understood before significant adoption of Lecanamab and similar drugs.
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