BREAKING NEWS: Alzheimer’s Disease Drugs Make Patients' Brains Shrink
Brain shrinkage and worsening cognition found in response to several AD drugs
A new review of 31 clinical trials of drugs used to treat Alzheimer’s disease (AD) has shown that “different classes” of AD drugs “accelerated brain atrophy” or shrinking, MEDPAGE Today reported March 31. (1)
This review article focused on drugs that attempt to rid the brain of the beta-amyloid protein plaques and tangles that are characteristic of AD brains on autopsy. Two types of drugs were examined: secretase inhibitors, “which have failed in clinical trials and worsened cognition”; and monoclonal antibody drugs, “including two drugs with accelerated FDA approvals, aducanumab (Aduhelm) and lecanemab (Leqembi),” according to MEDPAGE Today.
Verubecestat is an example of a secretase inhibitor drug. In 2019, MEDPAGE Today reported that Stage III clinical trials of verubecestat were ended abruptly when “both cognition and daily function,” as well as brain imaging, were worse among AD patients taking the drug than in those taking a placebo. (2)
Verubecestat is in a class of drugs called a “BASE-1 inhibitor”—which we’ll go into in depth if one of them is ever shown to be effective—that is meant to stop the accumulation of amyloid protein plaques and tangles. Three of this class of drugs had already failed when the verubecestat Stage III clinical trial was ended abruptly in 2019 because the patients taking it were getting worse: There was a measurable decline in cognition in patients taking verubecestat. (2)
The new report also examines AD drugs that are linked to brain shrinkage (one of the hallmarks of advanced-stage disease). Both Aduhelm and Lequembi are “monoclonal antibody” drugs (something else we’ll examine in depth when they actually help patients). (1)
Aducanumab “targets beta-amyloid, a protein that accumulates in the brain and is associated with the development of Alzheimer's,” Seniors Bluebook explains. Lecanemab, now trade named Leqembi, targets “a different structure of beta-amyloid, called N3pG, which is believed to play a key role in the formation of amyloid plaques in the brain.” (3)
Although Aducanumab and Leqembi are both monoclonal antibody drugs that attack amyloid proteins as described above, their mechanisms of action differ: Aducanumab removes beta-amyloid protein from the brain; Leqembi blocks the formation of amyloid plaques. Both of these drugs are associated with brain shrinkage in treated patients. (1)
According to MEDPAGE Today, “Brain shrinkage—a reduction in brain volume or an increase in the volume of the brain's ventricles—typically is associated with Alzheimer's progression. Why it occurs after treatment with anti-amyloid drugs isn't known.” (3)
These findings were originally published in the journal Neurology by Scott Ayton, PhD, and his colleagues at the University of Melbourne. (4)
Ayton told MEDPAGE Today, “Monoclonal antibodies caused about a 40% acceleration to enlargement of the lateral ventricle, which is a classic marker of neurodegeneration. ... These findings call for an urgent re-evaluation of clinical trial data on brain volume and ARIA [amyloid-related imaging abnormalities].” (2)
In summary: Some drugs meant to treat AD instead cause cognition, daily functioning, and brain imaging to worsen; some cause the brain to shrink, as seen as Alzheimer’s disease advances. None of those is a desired outcome of AD treatment.
AUTHOR’S NOTE: For a more in-depth examination of some of these AD drugs, check out “Are Alzheimer’s Disease Drugs Failing Because They’re not Targeting the Viruses Now Found in AD Patients’ Brains?” on SubStack.
BIBLIOGRAPHY
1. Judy George. “Brains Shrink With Anti-Amyloid Alzheimer's Drugs—Treatments accelerate brain atrophy, but reasons why remain a mystery”; MEDPAGE Today, March 31, 2023. https://www.medpagetoday.com/neurology/alzheimersdisease/103817
2. Judy George. “BACE1 Inhibitor Worsens Cognition in Early Alzheimer's—Two trials spell doom for once-promising drug class”; MEDPAGE Today, April 10, 2019. https://www.medpagetoday.com/neurology/alzheimersdisease/79143
3. Kathleen Warshawsky, BSN, RN. “Aducanumab and Lecanemab: How are they different?” Seniors Bluebook, Febuary 6, 2023. https://seniorsbluebook.com/articles/aducanumab-and-lecanemab-how-are-they-different
4. Francesca Alves, Pawel Kallinowski, Scott Ayton. “Accelerated Brain Volume Loss Caused by Anti–β-Amyloid Drugs: A Systematic Review and Meta-analysis.” Neurology, March 27, 2023. DOI: https://doi.org/10.1212/WNL.0000000000207156
ABOUT THE AUTHOR
Neenyah Ostrom was the first reporter in the United States to report weekly for a decade on ME/CFS. Her reporting on the Chronic Fatigue Syndrome epidemic from 1988-1997 is getting increased attention thanks to Robert F. Kennedy Jr. He discusses her work extensively in his 2022 best seller, The Real Anthony Fauci. Ostrom’s groundbreaking reporting on Chronic Fatigue Syndrome and AIDS appeared in the New York Native from 1988 to 1997.
Ostrom wrote the Foreword to the recently published THE REAL AIDS EPIDEMIC: How the Tragic HIV Mistake Threatens Us All by Rebecca Culshaw, Ph.D.
Ostrom is the author of four books about the Chronic Fatigue Syndrome epidemic: What Really Killed Gilda Radner? Frontline Reports On The Chronic Fatigue Syndrome Epidemic (1991; TNM Inc., New York, NY), 50 Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS (1992; TNM Inc. and St. Martin’s Press, New York, NY; published in Japanese by Shindan-to-Chiryo, 1993; and in French by Les Editions Logiques, 1994), and America’s Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS (1993; TNM Inc., New York, NY); and America’s Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS, Updated 2nd Edition(2022, available as a Kindle ebook and paperback on Amazon.com). Her most recent book, Ampligen: The Battle for a Promising ME/CFS Drug (2022) is available as a Kindle ebook and paperback on Amazon.com
In 1995, Ostrom and New York Native were recognized as having reported one of the top 25 most-censored stories in the U.S. press by 1995’s Censored: The News That Didn’t Make The News And Why (The 1995 Project Censored Yearbook by Sonoma State University Professor Carl Jensen, introduction by Michael Crichton; published by Four Walls Eight Windows, New York, NY, 1995).
Ostrom is ghostwriter/editor of seven popular science books. Additionally, she was an editor of Total Breast Health: The Power Food Solution For Health And Wellness by Robin Keuneke, which was chosen as a Publishers Weekly “Best Book of 1998” in the category of Breast Health (Kensington Publishing Corp., April 1998).