Study focus: treatment of dementia

Of all the diseases that afflict us, dementia is one of the most terrifying because we see it coming and it is inexorable. It takes the mind but leaves the body. We have theories about what causes Alzheimer’s disease — tangles of a protein called beta-amyloid and over-expression of another protein called tau. These proteins in altered forms were thought to be a cause but removing them from most of the cells in the brain using monoclonal antibodies, did not improve symptoms by much. Perhaps the intervention was too late. Both proteins are probably involved but neither has been a fertile source of treatments, and most clinical trials have failed.

I worked in a Department of Pathology and Cell Biology at Columbia University Irving Medical Center where there are basic scientists and pathologists. A pathologist friend lamented the lack of progress for dementia and Parkinsonism as professionally embarrassing. Heart disease, inflammatory diseases, diabetes, cancer, and other conditions have fared better; there are new and effective treatments to extend life and restore independence, most stemming from basic research in cell biology.

There are many cures offered on the internet, but most are wishful thinking or fraud. One study bears watching: it suggested that vaccination for shingles, a painful rash caused by lingering chickenpox virus (Herpes zoster), reduces the number of cases of dementia in older people. Herpes zoster is a neurotropic virus, that selectively infects nerve cells, whose connections, or synapses in the parts of the brain dedicated to memory are the cellular basis of memory. Each nerve cell has 10,000 or more connections with other neurons.

The study in question hangs on a decision made by the UK’s National Health Service after the Shingrix vaccine became available in 2013. NHS decided to give the vaccine to people in Wales born after Sept. 1, 1933, but not to those born one week before. The two groups, in Wales, 80 years old in 2013, were otherwise identical.Each part of the study had thousands of patients.

The chickenpox vaccine reduced the number of people who became demented over the next 7 years by about 20%. The paper is from scientists at Stanford and several Swiss and German universities. It is tough statistical sledding to read but the data are serious. Twenty percent of patients is too few to be confident, but too many to ignore. See below for the reference.

There are many cures offered on the internet, but most are wishful thinking or fraud.

This experiment has been repeated by combining other data from England and Wales. This type of analysis, involving thousands of patient records, has become possible by keeping records in searchable databases. Other versions of the chickenpox vaccine experiment use a more effective vaccine that became available in 2023. Does the newer vaccine protect better than 20%?Does a vaccine applied when people are younger, or given repeatedly, slow the onset of dementia even better?

Think of a slow acting virus that destroys or inhibits neurons or the synapses involved in memory.It could be Herpes zoster lingering from childhood chickenpox or another virus. The vaccine could induce antibodies and T cells that would stop the progression of the slow virus and stave off dementia.A viral cause of dementia would be extraordinary. And actionable.

A second discovery that may be helpful is the effect of weight loss drugs like Wegovy on dementia. These drugs may also help a number of problems including drug addiction and alcohol abuse.

There are several ways to study the effect of these remarkable drugs. One takes advantage of the fact that loss of brain volume is amarker of Alzheimer’s disease. As the disease progresses damage spreads through the brain and it shrinks, which can be observed by magnetic resonance imaging.

One placebo-controlled trial analyzed 204 patients with mild Alzheimer’s disease at 24 clinics in the United Kingdom. Before the study began, all patients had magnetic resonance imaging of their brains to evaluate structure and volume. Half were given a daily injection of 1.8 milligrams of liraglutide/day, a drug used in weight loss and diabetes, while an equal number received a placebo.Those who received liraglutide lost less brain volume (about 50%) than untreated patients. Cognitive testing was done at 0, 24, and 52 weeks and researchers found that patients who received liraglutide hada slower decline in cognitive function — halfthat of untreated patients. They also said they felt better.

Like the Herpes zoster study the results are not conclusive but at this stage we are looking for a new approach, not miracles. Liraglutide and other GLP-1 analogues are licensed for obesity and diabetes, so its path to treatment for Alzheimer’sand other dementias could be relatively swift.

Two independent and larger phase 3 trials are underway, with results due at the end of 2025. If the results are correct, oneprediction would be that people who had been on weight loss drugs should not be entering memory care units. That analysis is difficult, and some of the databases are proprietary, but we will follow these experiments.

To join a study, go to clinicaltrials.gov. Use the search function.

A natural experiment on the effect of herpes zoster vaccination on dementia

https://doi.org/10.1038/s41586-025-08800-x

Dementia symptoms and areas of the brain

https://www.alzheimers.org.uk/about-dementia/stage...

Evaluation of Novel GLP-1 analogue in the treatment of Alzheimer’s disease

Authors: Paul Edison et al.

Volume: Volume20, IssueS6

DOI: https://doi.org/10.1002/alz.089799

Published: 09 January 2025

PDF: https://alz-journals.onlinelibrary.wiley.com/doi/p....…

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue licensed for the treatment of type 2 diabetes mellitus (T2DM). Preclinical evidence in transgenic models of Alzheimer’s disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers.

Richard Kessin, PhD is Emeritus Professor of Pathology and Cell Biology at the Columbia University Irving Medical Center.