麻豆传媒

PHILADELPHIA -- Blood biomarkers specific to Alzheimer's disease -- specifically, amyloid-beta 42/40 ratios and measures of phosphorylated tau 181 (p-tau181) -- had a relationship with subsequent dementia that started in midlife, a retrospective analysis showed.

These midlife biomarkers demonstrated long-term associations with late-life amyloid positivity and dementia diagnoses, reported Priya Palta, PhD, MHS, of the UNC School of Medicine in Chapel Hill, in a session presented at the Alzheimer's Association International Conference.

Dementia risk rose with each standard deviation (SD) change in midlife plasma amyloid-beta 42/40 ratio (HR 1.11, 95% CI 1.02-1.21) and in midlife plasma p-tau181 (HR 1.15, 95% CI 1.06-1.25), Palta and co-authors reported in a corresponding paper published in .

Late-life levels of amyloid, tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) also were associated with dementia. NfL is a measure of neuronal injury; GFAP reflects astrogliosis.

"This is a very important data set where they followed individuals, including a large proportion of African American individuals, over a number of decades," noted Stephen Salloway, MD, MS, of Brown University in Providence, Rhode Island, who led an accompanying the JAMA paper.

The findings mean that "as we move earlier in detection and earlier in preventive and risk reduction strategy, I see us eventually being able to detect who's at risk for Alzheimer's disease many years -- decades really, in midlife -- before the onset of symptoms, and then being able to institute either risk reduction and or biological treatments that modify that risk," Salloway said in a .

"We can't take these results directly now into testing people at midlife with large-scale screening," Salloway pointed out.

But the study "gives us a clue that we will be able to, as our precision increases and the sensitivity of our measures improves, so we can tell who's on the pathway to developing Alzheimer's disease many years before there's any impairment," he said. "That's really exciting. It's a little bit futuristic, but really exciting."

Palta and co-authors used data from the Atherosclerosis Risk in Communities Neurocognitive Study (), a study that recruited a diverse group of middle-aged adults in the late 1980s.

They analyzed data from 1,525 ARIC-NCS participants retrospectively. Blood biomarker data were collected at both midlife (mean age 58) and late-life (mean age 76) periods. Links between blood biomarkers and incident all-cause dementia were evaluated in a subpopulation of 1,339 participants who were dementia-free in 2011-2013 and had biomarker measurements in 1993-1995 and 2011-2013.

Overall, women made up 59.9% of the study population; Black participants made up 25.8%. Dementia was ascertained through neuropsychological assessments, participant or informant contacts, and medical record surveillance. Overall, 252 participants (16.5%) developed dementia in late life.

Decreasing amyloid-beta 42/40 ratios and increasing p-tau181, NfL, and GFAP were seen from midlife to late life, all indicating greater Alzheimer's pathology with aging. Biomarker changes occurred more rapidly in people who carried an APOE4 allele.

Midlife hypertension was associated with a 0.15-SD faster increase in NfL and a 0.08-SD faster increase in GFAP per decade. Midlife diabetes was tied to a 0.11-SD faster NfL increase and a 0.15-SD faster GFAP increase.

Only amyloid and tau biomarkers in midlife demonstrated long-term relationships with dementia. All biomarkers in late life, however, had statistically significant associations with late-life dementia. Plasma NfL had the strongest association (HR 1.92, 95% CI 1.72-2.14).

"There is a shortage of research on blood biomarker changes in individuals in their mid- to late-life, especially in diverse community-based cohorts, and on the relationships between biomarker changes and midlife cardiometabolic disorders," Palta said.

"Understanding these biomarker relationships could provide us further insights into how we can help maintain brain function in people at risk for dementia, monitor disease progression, or identify individuals who may benefit from treatment," she added.

The study had several limitations, the researchers noted. Plasma biomarkers were measured at three time points at most. Only modest associations between p-tau181 and incident dementia were observed in this study; other p-tau assays, like p-tau217, may produce better results.