June 27, 2019
In recent years, one promising Alzheimer’s drug after another has failed to produce results in clinical trials. At the same time, the growing number of older adults with cognitive problems is reaching a crisis point. In 2018, there were 5.7 million people in the United States living with Alzheimer's disease. That number is projected to grow to 13.8 million by 2050, threatening to overwhelm the U.S. healthcare system.
One problem with the search for treatments to date has been our limited understanding of what causes dementia. In 1906, when Alois Alzheimer, a German psychiatrist and neuropathologist, first described a patient with an unusual disease that caused her mental deterioration and premature death at 55, he noticed accumulations of plaques on her brain that had previously been found only in much older, senile patients.
Working from that starting point, scientists began diligently looking for the substances causing the brain changes. In 1984, George Glenner identified a protein called amyloid that builds up in the plaques of Alzheimer patients’ brains.
For the past three decades, the bulk of dementia drug development has been based on that discovery. New drugs have been aimed at decreasing the amount of amyloid in the brain, and some were successful in doing so. The problem was that even with lowered levels of amyloid, memory loss persisted, according to two papers published in 2014 in the New England Journal of Medicine.
The failures have made clear that amyloid is only part of the problem and that research must also focus on other factors contributing to memory loss.
Fortunately, we have clues. One dates back to a 1997 study by David Snowdon and his colleagues at the University of Kentucky. Snowdon recruited 678 members of the Roman Catholic School Sisters of Notre Dame, an order of non-cloistered nuns who taught children in different parts of the country. He tracked the sisters to see which of them developed dementia and then examined their brains after they died.
The sisters were an excellent cohort for research because of the similarities in their lifestyles and because each woman’s medical history could be matched with extensive records kept by the order. This rich information continues to reveal new indicators for brain health later in life.