A recent study indicates that the decrease in brain volume linked to new Alzheimer’s disease immunotherapies may stem from the elimination of amyloid plaques rather than from neural loss or overall brain activity reduction.
A recent study led by researchers from UCL suggests that the decrease in brain volume associated with innovative immunotherapies for Alzheimer’s disease could be due to the elimination of amyloid plaques, rather than the loss of neurons or brain matter.
This research, published in Lancet Neurology, analyzed data from twelve distinct trials focusing on amyloid-targeting immunotherapies, including lecanemab, which has recently received approval from the UK’s MHRA regulator.
Although brain shrinkage is typically seen as a negative outcome, the research team noted that the increased volume loss was consistent across various studies and correlated with the therapy’s effectiveness in eliminating amyloid; it did not demonstrate any harmful effects.
The researchers believe that the changes in brain volume observed could primarily result from the removal of amyloid plaques, which are frequently found in Alzheimer’s patients, suggesting that this volume loss may not be something to worry about.
To label this phenomenon, the research team introduced the term “amyloid-removal-related pseudo-atrophy,” or ARPA.
Professor Nick Fox, the senior author and Director of the UCL Dementia Research Centre, stated: “Amyloid-targeting monoclonal antibodies represent a major advancement in Alzheimer’s disease treatment. These antibodies work by binding to amyloid plaques and facilitating their removal from the brain.”
“One point of contention has been the impact of these treatments on brain volume. Loss of brain volume is a common characteristic of Alzheimer’s disease due to the gradual loss of neurons.”
“However, amyloid immunotherapy has repeatedly shown an increase in brain volume loss, raising concerns in the media and medical literature about potential, unrecognized harm to the brains of treated patients.”
“Yet, based on the existing data, we believe that this increase in volume change is a predictable result of removing harmful amyloid plaques from the brains of Alzheimer’s patients.”
Dr. Christopher Belder, the first author from the UCL Dementia Research Centre and The University of Adelaide, added: “We urge improved documentation of these changes in clinical trials and further analysis to gain a clearer understanding of how these therapies affect brain volume as they become more widely used.”
In August, the Medicines and Healthcare Products Regulatory Agency (MHRA) approved lecanemab for use in the early stages of Alzheimer’s disease in the UK.
This medication works by targeting beta amyloid, a protein that accumulates in the brains of individuals with Alzheimer’s and is believed to trigger neuronal dysfunction and cell death.
The National Institute for Health and Care Excellence (NICE), which determines whether drugs should be available through the NHS, has released draft guidance indicating that the advantages of lecanemab are too minor to warrant its cost to the NHS. However, this decision will be reconsidered following public consultations and a second independent committee meeting later in the year.
