Amyloid beta levels in blood may indicate risk for cognitive decline

Decreased levels of plasma amyloid beta 42 at midlife, but not late life, correlated with an increased risk for dementia and a “marginally higher” risk for mild cognitive impairment, according to findings published in Neurology.

The study, which was derived from a subsample of the Atherosclerosis Risk in Communities cohort, also demonstrated that increased levels of plasma amyloid beta 40 increased risk for mild cognitive impairment and dementia whether it was measured during midlife or late life. Together, the findings indicated that midlife measurements of plasma amyloid beta “may have utility” as a blood-based biomarker for future risk of cognitive impairment, according to the researchers.

“Right now, we look at levels of the protein amyloid beta in the central nervous system as a biomarker of Alzheimer’s disease, but the only way to do that is through brain scans or looking at the cerebrospinal fluid via a lumbar puncture,” Kevin J. Sullivan, PhD, MPH, of the University of Mississippi Medical Center, said in a press release. “These new results suggest that there is utility in using simple blood draws that would be less expensive and much less invasive for people.”

Sullivan and colleagues aimed to determine the relationship between levels of amyloid beta, including amyloid beta 1-42, 1-40 and 42:40, and risks for mild cognitive impairment and dementia. Researchers prospectively examined levels of amyloid beta using a fluorimetric, bead-based immunoassay among the subsample of patients in the Atherosclerosis Risk in Communities cohort study, which included patients aged 45 to 64 years. Between 2011 and 2019, researchers conducted measurements at midlife and late life and analyzed changes from one period to another in risk for mild cognitive impairment, dementia and combined mild cognitive impairment/dementia later in life. Multinomial logistic regressions estimated relative RRs for these cognitive outcomes compared with cognitively normal individuals, with adjustments for age, sex, education, site-race, APOE status, hypertension, diabetes and BMI.

The analysis included 2,284 participants with a mean age of 59.2 years at the time of the midlife plasma amyloid beta measurement (57% women; 22% Black). Sullivan and colleagues reported an average amyloid beta 42:40 ratio of 0.21±0.12 at midlife. At the time of the late-life plasma amyloid beta measurements (average age, 76.97 years), researchers reported an average amyloid beta 42:40 ratio 0.17±0.08.

Sullivan and colleagues found that each doubling of midlife amyloid beta 42:40 ratio was linked to a 37% reduced risk for mild cognitive impairment/dementia (relative RR = 0.63; 95% CI, 0.46-0.87), “but only up to approximately the median (spline model threshold, 0.20).” Every standard deviation increase in plasma amyloid beta 42 (10 pg/mL) correlated with a 13% reduced risk for mild cognitive impairment/dementia (relative RR = 0.87; 95% CI, 0.77-0.98), whereas every standard deviation increase in plasma amyloid beta 40 (67 pg/mL) correlated with a 15% increased risk for mild cognitive impairment/dementia (relative RR = 1.15; 95% CI, 1.01-1.29).

Researchers found that associations were comparable, but slightly weaker statistically, when they repeated models using late-life plasma amyloid beta predictors. Specifically, amyloid beta 42 and amyloid beta 40 rose from midlife to late life, but these increases were not linked to cognitive outcomes, according to the study results. Additionally, they observed the same results following adjustments for factors that could have impacted cognitive impairment, such as age, education and cardiovascular risk factors, according to the press release.

Sullivan and colleagues acknowledged, in addressing the limitations of the study, that the use of an older testing method to assess blood levels of amyloid beta did not provide results that were “as precise as newer methods of testing,” according to the press release. In addition, the study did not prove that the blood test could be used to predict who would develop dementia later in life.

“A doubling of this ratio under this threshold at midlife was associated with a 37% lower risk of [mild cognitive impairment] or dementia, which is comparable to about [5] years of younger age, and a doubling of this ratio under this threshold at late life was comparable to about [3] years younger age,” Sullivan said in the press release. “Amyloid in the blood may be useful as a biomarker for risk of future cognitive impairment.”

Reference:

American Academy of Neurology. Could blood tests help determine risk of Alzheimer’s disease early? Available at: https://www.aan.com/PressRoom/Home/PressRelease/4915. Accessed Aug. 9, 2021.