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Dr. Ron Brookmeyer’s research on preclinical Alzheimer’s may offer clues into how to prevent or delay the disease’s progression.
Alzheimer’s disease is the sixth-leading cause of death in the United States. There is no cure for the disease and little is known about how to prevent it. As the U.S. population ages, the number of Americans with Alzheimer’s disease or mild cognitive impairment (a condition marked by a decline in memory and thinking skills that can be a precursor to Alzheimer’s) will more than double in the next 40-plus years, from 6.08 million in 2017 to 15 million in 2060, according to research led by Dr. Ron Brookmeyer, professor of biostatistics at the UCLA Fielding School of Public Health.
The findings of Brookmeyer’s research group provide a sobering picture of the mounting public health crisis, but may also offer insights for researchers seeking strategies to mitigate the disease’s societal toll. In addition to its projections related to Alzheimer’s disease and mild cognitive impairment, Brookmeyer’s team has focused on people with preclinical Alzheimer’s disease — biological changes in the brain that can occur a decade or more prior to the person exhibiting any obvious signs of the disease. These early brain changes are confirmed by biomarker tests that detect an abnormal buildup of protein fragments in the brain or a decrease in brain volume. The team’s findings on preclinical Alzheimer’s may offer clues into how to prevent or delay the disease’s progression.
In a paper published in February, Brookmeyer and colleagues, including Nada Abdalla, a biostatistics doctoral student at the Fielding School, described a mathematical modeling tool that incorporates data from studies that have measured biomarkers and tracked Alzheimer’s disease progression in thousands of people. They found that in 2017, 46.7 million Americans had preclinical Alzheimer’s disease. Brookmeyer and Abdalla followed up that study with another paper published in May that included lifetime and 10-year risk estimates for Alzheimer’s disease-related dementia based on a person’s gender, age and whether or not the person has preclinical disease or mild cognitive impairment. According to the researchers’ projections, most people with preclinical signs of Alzheimer’s disease will not go on to develop the dementia that occurs during the later stages of the disease.
Brookmeyer notes that many trials of Alzheimer’s disease treatments that have failed to prove efficacy were conducted in people in late stages of the disease, leading many researchers to question whether clinical trials with patients in these earliest, preclinical disease stages might prevent or delay its progression. Brookmeyer believes his research showing that Alzheimer’s disease has a long preclinical course highlights that there is an opportunity to intervene early and develop treatments and strategies to delay the onset of symptoms. “It’s an important message that if people come up positive on these biomarkers it is not a given that they will get clinical dementia in their lifespan,” he says. “And as new interventions are developed, people who fall into the preclinical disease category may be good candidates for clinical trials.”
Forecasting the Prevalence of Preclinical and Clinical Alzheimer's Disease in the United States (Alzheimer’s & Dementia) | LINK
Estimation of lifetime risks of Alzheimer's disease dementia using biomarkers for preclinical disease (Alzheimer’s & Dementia) | LINK
A stochastic estimation procedure for intermittently-observed semi-Markov multistate models with back transitions (Statistical Methods in Medical Research) | LINK
Preclinical Alzheimer's Already Affects Nearly 47 Million in US (Reuters Health) | LINK