Blood Biomarker Study Reveals Early Signals of Future Cognitive Difficulties

Alzheimer’s disease develops silently over many years, while subtle memory changes can elude standard cognitive testing. Blood-based measures are being explored as scalable, minimally invasive tools for detecting early neurodegenerative changes. Clarifying which biomarkers align with distinct cognitive domains could refine risk assessment in older adults. 

University of Miami Miller School of Medicine (Miami, FL, USA) researchers evaluated plasma phosphorylated tau 181 (p-tau181) alongside glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta 42/40 in a population-based cohort. 

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The team examined these Alzheimer’s-related and neurodegeneration-associated blood biomarkers as continuous measures rather than positive or negative results. They then compared biomarker levels with performance across specific cognitive domains, including memory, executive function, language, visuospatial ability, and overall cognition.

The analysis included 1,170 older adults with an average age of 73 years who completed extensive cognitive testing in 2016 and again in 2022. At baseline, 931 participants were cognitively normal, 206 had mild cognitive impairment, and 33 had dementia. Investigators assessed whether biomarker levels at the time of blood draw related to cognition at baseline and six years later.

Higher p-tau181 levels were not linked to memory performance at the initial assessment but were associated with poorer memory six years later, even after accounting for baseline memory and the other biomarkers. At baseline, NfL and GFAP showed the broadest associations, correlating with memory, executive function, and global cognition. Six years later, p-tau181 remained independently associated with lower memory and global cognition, while GFAP was linked to poorer memory, executive function, and overall cognition. NfL and amyloid beta 42/40 were no longer independently associated after adjustment. Findings were largely unchanged when analyses were limited to participants who were cognitively normal at baseline.

Published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring on September 8, 2026, the study suggests that subtle biological changes detectable in blood may precede measurable memory decline by years.

Although blood tests are less invasive and more accessible than imaging or cerebrospinal fluid collection, the researchers emphasized that the work was not designed to predict whether a specific individual will develop Alzheimer’s disease, mild cognitive impairment, or dementia. The biomarker associations explained only modest additional variation beyond established risk factors and baseline performance, and additional studies with repeated blood testing and longer follow-up are needed.

“p‑tau181 was not associated with memory at the initial assessment, but it was associated with memory performance six years later. That suggests these blood markers may provide information about future cognitive vulnerability that is not apparent from cognition measured at the same point in time,” said Deirdre O’Shea, Ph.D., assistant professor of cognitive neurology at the University of Miami Miller School of Medicine. 

“Blood biomarkers are often discussed as positive or negative tests, but biology exists on a continuum. By examining biomarker levels across their full range and looking separately at memory, executive functioning and other cognitive abilities, we could see patterns that would be lost by reducing either the biomarker or cognition to a single category,” added Dr. O’Shea.

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University of Miami Miller School of Medicine