The lifetime risks for a female with only amyloidosis are 8.4% for a 90-year-old and 29.3% for a 65-year-old, but persons younger than 85 years with mild cognitive impairment, amyloidosis, and neurodegeneration have lifetime risks of AD dementia greater than 50%.
Ron Brookmeyer, PhD, MS
The lifetime risks of Alzheimer disease (AD) dementia vary considerably by age, gender, and the preclinical or clinical disease state of the individual, according to a new analysis.
Findings revealed that, for example, a 60-year-old woman without any biomarkers for AD has about a 20% chance of developing AD dementia, while a woman of the same age with biomarkers that already has shown some decline in memory and thinking skills would have a 96% chance.
“Lifetime risk estimates can help doctors and other health care providers evaluate whether or not a positive screening test means a patient is likely to develop Alzheimer’s disease dementia,” Ron Brookmeyer, PhD, MS, a professor of biostatistics at the UCLA Fielding School of Public Health, said in a statement. “These estimates may reassure some people that despite testing positive on screening tests, their chances of developing Alzheimer’s disease dementia are low.”
Brookmeyer told MD Magazine that these data imply that biomarkers should be interpreted cautiously. Ultimately, he said that they should provide some clarity to the clinical interpretation of screening results to patients, which could provide some assurance.
“Most [biomarkers] are being used for research purposes and haven’t largely entered the clinical arena, although they will as they become more specific and sensitive,” he said. “These lifetime risks help put into perspective what a positive biomarker would mean from a clinical point of view.”
Brookmeyer and doctoral candidate Nada Abdalla used a multistate model for the progression of AD through its preclinical and clinical stages to conduct the study. Transition rates were determined included 1541 patients from the Mayo Clinic Study of Aging and another including 353 patients with MCI, amyloidosis, and neurodegeneration, and 222 with mild cognitive impairment (MCI) and neurodegeneration.
There were 7 states of AD used to examine the lifetime risk at 5-year intervals from ages 60 to 90 years. They were as follows: State 1, normal; State 2, amyloidosis; State 3, neurodegeneration; State 4, amyloidosis and neurodegeneration; State 5, AD MCI with neurodegeneration and amyloidosis; State 6, AD MCI with neurodegeneration; State 7, AD dementia.
The results showed that the lifetime risks of AD dementia for both women and men were similar at each age and increased by disease state in the following order: State 1, State 3, State 2, State 4, State 6, and State 5.
When comparing lifetime risks by age and gender, regardless of preclinical or clinical states, finding that women had an overall higher risk of AD dementia. For women and men, respectively, the risk at age 60 was 24.4% (95% CI, 13.1—39.8) and 17.6% (95% CI, 9.0–30.8), at age 70 was 26.2% (95% CI, 14.3–41.9) and 19.9% (95% CI, 10.3–33.7), at age 80 was 27.7% (95% CI, 15.7–39.5) and 21.8% (95% CI, 11.9–34.7), and at age 90 was 23.2% (95% CI, 14.0–33.2) and 18.2% (95% CI, ­­10.6–27.0).
“Some of these numbers actually show that the risks can get very high, particularly if they have early clinical symptoms, like MCI,” Brookmeyer said. “For example, a 70-year-old male with only amyloid is at 20% lifetime risk. You add neurodegeneration and it climbs to 31%. But if you add MCI on top of that, the risk climbs to 86%.”
The presence of preclinical disease was not found to necessarily hint at a high likelihood of AD dementia. For example, a 90-year-old woman in State 2 has a lifetime risk of AD dementia of 8.4% compared with a 29.3% lifetime risk for a 65-year-old in State 2—explained by a shorter life expectancy for the 90-year old. According to Brookmeyer and Abdalla, MCI in the presence of both amyloidosis and neurodegeneration presents a lifetime risk of at least 50% for all ages ≤85 years.
Brookmeyer said that the most surprising finding was how low the lifetime risk related to the presence of the preclinical biomarker amyloid was. “We always hear about amyloid and when we looked at this, [we realized] it’s not what you might first think it means in terms of what your risks are. You’re more likely to not have dementia than you are,” he said.
A previous study from Brookmeyer and colleagues revealed that the prevalence of AD is expected to more than double by 2060—estimating that 15 million will have the condition in the US. Although that study did reveal that 47 million Americans have the preclinical signs of AD without clinical indications, “actually many of these people may never progress to clinical disease in their lifetime,” Brookmeyer said.
The study, “Estimation of lifetime risks of Alzheimer’s disease dementia using biomarkers for preclinical disease,” was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
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