Alzheimer Disease (AD) is the most common cause of dementia, a condition that impairs intellectual functioning, including, but not limited to, memory impairment, social dysfunction, and compromise of abstract thinking.  It is the most common cause of dementia in the US.  Currently, almost six million Americans are afflicted with dementia, and demographers project this number to be 14 million in 2060.  Dementia is already a true public health problem and threatens to be a disaster if the projections are correct.  This is why recent, though modest, advances in the search for the treatment of Alzheimer’s Disease are so important

Background 

The hallmark of AD is the presence of amyloid plaques in the brain.  Demonstrable by PET scanning, or examination of cerebral spinal fluid obtained by means of a spinal tap, these are clumps of protein that are associated with damage to the brain cells of people with AD.* 

The question is whether they are a cause of the disease or a result.  It is a complex question, especially since many cognitive normal people also have these plaques. 

Monoclonal Antibodies

Nevertheless, research has centered on these plaques, and there are now interventions that attack, and remove, these plaques.  They are anti-amyloid monoclonal antibodies, and they have won FDA (Food and Drug Administration) approval.

Recent Clinical Trials

In August, the Journal of the American Medical Association published the results of a clinical trial of the newest anti-amyloid drug, donanemab.  1736 patients with mild dementia were randomized to a trial of donanemab vs. placebo.  They were observed for 18 months and were tested for cognitive decline (Alzheimer Disease Rating scale).  

At the end of the trial, those who got the drug on average showed significantly slower clinical progression to worsening dementia compared to those who got placebo.  47% of the group who received donanemab had no disease progression, while 29% of placebo recipients did not progress to worsening dementia, as measured by cognitive testing. The drug showed an impressive ability to remove the amyloid plaques from the brain.  In no patients was the progress of disease reversed.

The upshot is that donanemab slowed progression to a worsening cognitive state in patients with mild dementia by a quarter to a half a year.  The worse the dementia, the less effective was the drug.

Side Effects and Cost

The intervention group had a greater number of side effects, notably brain swelling and micro-hemorrhages.  These were usually clinically unimportant and resolved with cessation of the drug.  There were three deaths in the treatment group and one in the placebo group.

Treatment required monthly intravenous infusions.  The launch price for the drug is $28,000, and at least a similar amount is necessary to cover the cost of required monthly MRIs, follow-up visits, and more.  Medicare is reimbursing the expense, provided patients are enrolled in a registry that collects data that monitor safety and efficacy.  Copays will amount to about $15,000 a year.

Genuine Progress

Unlike some highly advertised and ineffective therapies for memory problems (see my blog of May 28, 2022: “Prevagen!… Prevagen?”), the anti-amyloid antibodies represent authentic advances in the treatment of AD.  However, much work remains to determine whether this line of research will become a mainstay in the treatment of AD.  A critical question is whether the healthcare system can afford it.  I don’t know the answer, but I do know what those afflicted with AD and their families will say.

Science Marches On

Like all good science, the current research engenders more questions than answers.  Perhaps the most compelling area of inquiry concerns the possibility of prevention of AD. For instance, what if you give the anti-amyloid antibody to people at risk for the disease before they develop symptoms or plaques?  Would this actually prevent, or at least ameliorate, AD?  No one knows but trials to test this notion are underway.

*Other causes of dementia include cerebrovascular disorders (which is the result of multiple strokes, often subclinical), Lewy body dementia, frontotemporal dementia, and Parkinsons.  None of these is associated with the amyloid plaques, although AD may overlap with any of these disorders.