"We were surprised by the magnitude of the numbers. We found that, in 2017, 46.7 million Americans had preclinical Alzheimer's disease – amyloidosis, neuro-degeneration, or both – although many of those people will not progress to clinical Alzheimer's disease during their natural lifespan," lead author Dr. Ron Brookmeyer, a professor of biostatistics at the University of California, Los Angeles, told Reuters Health by telephone.
In what Dr. Brookmeyer and colleagues describe as the first study to provide population-level preclinical disease forecasts, they searched PubMed for worldwide literature about preclinical and clinical AD prevalence.
The researchers used a multistate model of AD progression through eight stages, from normal to late clinical AD. The model incorporated biomarkers for preclinical AD with U.S. population projections, accounting for trends in aging. The findings were published online December 6 in Alzheimer's & Dementia.
Summarizing the results, Dr. Brookmeyer said, "We're expecting more than a doubling in the number of people with clinical disease. We estimated that, in 2017, there were approximately 6.08 million Americans who had either Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease. We expect that to grow to 15 million by 2060. We currently estimate that about 2.4 million Americans are now living with mild cognitive impairment (MCI), a precursor condition where people have not yet reached the threshold for dementia."
The researchers further estimate that, from 2017 to 2060, the number of people in the U.S. with only amyloidosis will rise from roughly 22.1 to 31.9 million; that those with only neurodegeneration will climb from about 8.3 to 13.6 million; those with both amyloidosis and neurodegeneration from 16.2 to 30.2 million; those with AD-related MCI from 2.4 to 5.7 million; and those with clinical AD from 3.7 to 9.3 million.
Dr. James Leverenz, director of the Cleveland Clinic Lou Ruvo Center for Brain Health Center, in Ohio, told Reuters Health by email that this study underscores what researchers have been expecting: As our society ages, the number of people with preclinical AD will increase dramatically.
"We know that the changes of Alzheimer’s disease occur in the brain years, if not decades, before the symptoms emerge. New therapies for Alzheimer’s disease are increasingly focused on treating people before they develop symptoms, with the idea of preventing the development of dementia and hitting the disease when it may be more responsive to these therapies," said Dr. Leverenz, who was not involved in the study.
"Given the millions of preclinical Alzheimer’s disease cases outlined in this study, we will need to develop accurate and economical ways to identify these individuals so that these new therapies can be utilized," he advised. "The next step is how to best identify these individuals so that, when a preventative therapy becomes available, we can utilize it immediately."
"We are facing a very challenging future, given this tsunami of preclinical and symptomatic Alzheimer’s disease," Dr. Leverenz noted. "This is, and will be, a major public health problem. However, there’s reason to be hopeful given the recent increases in government funding for research on Alzheimer’s disease and related disorders as well as the continued efforts from advocacy groups such as the Alzheimer’s Association and the commitment of industry to develop new and better therapies."
Dr. Brookmeyer said that research has identified “tantalizing new clues about the pathogenesis and natural history of Alzheimer's disease”; that biomarker tests that do imaging and scan for amyloid can detect brain damage or neurodegeneration, indicating whether a patient is on the path toward AD; and that biomarkers are becoming more refined and accurate.
Most of these tests are being used in research, he noted, but he wondered whether they should be used in routine clinical care.
Looking ahead, Dr. Brookmeyer said, "We are currently working on identifying other factors that can indicate which people are more likely to progress during their lifespan. That depends on the stage of preclinical disease they're in; whether they have amyloid buildup or neurodegeneration; and on their age, because a 65-year-old found to have amyloid has a longer time than a 90-year-old to progress to AD during the natural lifespan."
"Many of the numbers we have rely on a few excellent longitudinal cohort studies in the literature," he explained, "but the populations they were based on were not as diverse as we would like, so we want to look at new studies that may be coming out that may refer to more diverse populations"
"This is an exciting time to see the exponential growth in knowledge about the disease. Hopefully, this will ultimately lead not only to treatment but to primary prevention," he noted.