Summary: Lower blood levels of amyloid-beta 42 during mid-life were associated with a higher risk of dementia and a marginally increased risk of mild cognitive impairment later in life, a new study reports.
A new study used a simple blood test to find that people who later developed dementia or mild cognitive impairment had a lower level of a protein called amyloid beta 42 (Aß42) in their blood at midlife than those who did not.
The research is published in the August 4, 2021, online issue of Neurology.
“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,” said study author Kevin J. Sullivan, PhD, MPH, of the University of Mississippi Medical Center in Jackson. “These new results suggest that there is utility in using simple blood draws that would be less expensive and much less invasive for people.”
The study involved 2,284 people with an average age of 59 who did not have problems with memory or thinking skills at the start of the study. The people’s blood level of amyloid beta was tested with samples from the beginning of the study, which the researchers called the midlife test, and then again when they were about 77 years old, or the late life test.
The people were given thinking and memory tests over the 25 years of the study to determine whether they developed dementia or mild cognitive impairment (MCI), which is problems with memory and thinking skills that can be a precursor to dementia. A total of 502 people developed dementia and 832 developed mild cognitive impairment.
The researchers looked at levels of both Aß42 and amyloid beta 40 (Aß40), and the ratio between the two.
They found that lower levels of Aß42 at midlife, but not late life, was associated with the higher risk of dementia and marginally higher risk of mild cognitive impairment. Every 10 picogram per milliliter (pg/mL) increase in the blood of Aß42 was associated with a 13% lower risk of MCI or dementia.
But higher levels of Aß40 were associated with higher risk of dementia and MCI at both midlife and late life. Every 67 pg/mL increase in the blood of Aß40 was associated with a 15% increased risk of MCI or dementia.
A lower ratio of Aß42 to Aß40 was associated with a higher risk of dementia and MCI, but only up to the median level. After that, an increase in the ratio was not related to risk of dementia.
“A doubling of this ratio under this threshold at midlife was associated with a 37% lower risk of MCI or dementia, which is comparable to about five years of younger age, and a doubling of this ratio under this threshold at late life was comparable to about three years younger age,” Sullivan said.
“Amyloid in the blood may be useful as a biomarker for risk of future cognitive impairment.”
The results were the same after researchers adjusted for other factors that could affect cognitive impairment, such as age, education and cardiovascular risk factors.
A limitation of the study was that an older testing method was used to estimate blood levels of amyloid beta that is not as precise as newer methods of testing.
The study does not prove the blood test can be used to predict who will develop dementia later in life.
Funding: The study was supported by the National Heart, Lung, and Blood Institute, National Institute for Neurological Disorders and Stroke, National Institute on Aging and National Institute on Deafness and Other Communication Disorders.
About this dementia research news
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Association of Midlife Plasma Amyloid-β Levels With Cognitive Impairment in Late Life: The ARIC Neurocognitive Study
To evaluate the association between midlife plasma amyloid-beta (Aβ1-42, Aβ1-40, Aβ42:Aβ40) and risk of MCI and dementia.
Plasma Aβ42 and Aβ40 were retrospectively measured using a fluorimetric bead-based immunoassay in a subsample of the Atherosclerosis Risk in Communities cohort study. We investigated the relationship of plasma Aβ42, Aβ40, and Aβ42:Aβ40 ratio measured in midlife, late-life, and the change from midlife to late-life, to risk of MCI, dementia, and combined MCI/dementia outcomes in late-life (from 2011-19). We used multinomial logistic regressions estimating relative risk ratios (RRR) of these cognitive outcomes vs cognitively normal adjusted for age, sex, education, site-race, APOE, hypertension, diabetes, and body mass index.
A total of 2284 participants were included (midlife mean age=59.2±5.2, 57% female, 22% Black). Each doubling of midlife Aβ42:Aβ40 was associated with 37% lower risk of MCI/dementia (RRR=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 Aβ42 (10 pg/mL) was associated with 13% lower risk of MCI/dementia (RRR=0.87, 95% CI: 0.77, 0.98), whereas every standard deviation increase in plasma Aβ40 (67 pg/mL) was associated with 15% higher risk of MCI/dementia (RRR=1.15, 95% CI: 1.01, 1.29). Associations were comparable, but slightly weaker statistically, when repeating models using late-life plasma Aβ predictors. Aβ42 and Aβ40 increased from midlife to late-life, but changes were not associated with cognitive outcomes.
Midlife measurement of plasma Aβ may have utility as a blood-based biomarker indicative of risk for future cognitive impairment.