Blood Biomarkers and Cognitive Testing Improve Prediction of Early Alzheimer’s Decline
A University of Miami Miller School of Medicine study found that combining blood-based biomarkers with specialized cognitive testing significantly improves prediction of functional decline in older adults at risk for Alzheimer’s disease, offering a more precise approach to early diagnosis and monitoring.
A new study led by Diane Zheng, Ph.D., at the University of Miami Miller School of Medicine suggests that combining blood-based biomarkers with specialized cognitive testing can significantly improve prediction of functional decline in older adults at risk for Alzheimer’s disease.
Published in the Journal of Alzheimer’s Disease, the research highlights a central challenge in Alzheimer’s care. While biological markers can reveal disease pathology, they do not necessarily predict whether patients will develop clinical symptoms. By integrating biological and cognitive measures, the study offers a more precise way to assess disease progression in its earliest stages.
“Our study suggests that combining blood biomarkers with a sensitive cognitive test will help clinicians better identify which patients with early cognitive impairment are more likely to experience future decline,” said Dr. Zheng, a research assistant professor of psychiatry and behavioral sciences at the Miller School.
David Loewenstein, Ph.D., professor of neurology, psychiatry and behavioral sciences at the Miller School and a nationally recognized expert in cognitive aging, and Rosie Curiel Cid, Psy.D., scientific director of the Center for Cognitive Neuroscience and Aging (CNSA) and professor of psychiatry and behavioral sciences at the Miller School, joined Dr. Zheng on the study.
A Complementary Diagnostic Strategy
Plasma biomarkers such as phosphorylated tau (p-tau217), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as accessible indicators of Alzheimer’s disease pathology. Biomarker abnormalities, though, can precede symptoms by years. Some people with detectable pathology never experience meaningful decline.
To bridge this gap, Dr. Zheng, Dr. Loewenstein and Dr. Curiel Cid incorporated cognitive challenge tests, specifically the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L). The LASSI-L test was developed at the CNSA. These tests measure subtle deficits in memory processing, including a patient’s ability to override previously learned information when taking in new material.
Study Design and Methods
The longitudinal study followed 159 adults between ages 54 and 98 who had cognitive impairment without dementia at baseline. Participants were enrolled through the 1Florida Alzheimer’s Disease Research Center and completed comprehensive clinical, neuropsychological and biomarker assessments.
Each participant underwent at least three annual evaluations over an average follow-up of approximately 41.5 months. Researchers measured cognitive and daily functioning using the Clinical Dementia Rating–Sum of Boxes, a widely used measure that captures impairment across domains such as memory, judgment and personal care. They then examined the changes over time using latent growth curve modeling techniques.
Blood samples were analyzed for p-tau217, GFAP and NfL using high-sensitivity assays. Cognitive testing focused on recall performance and intrusion errors associated with semantic interference tasks.
Results: Distinct but Complementary Signals
The findings show that biomarkers and cognitive testing each capture different aspects of disease progression and are most useful when combined.
Overall, participants demonstrated gradual worsening over time, with increasing variability in cognitive and functional scores.
Levels of plasma p-tau217 were strongly associated with baseline functional status. NfL consistently predicted the rate of functional decline over time, even after adjusting for demographic, genetic factor and amyloid PET status.
At the same time, deficits in cognitive challenge testing contributed independently to predict worsening function. In particular, reduced recall and increased intrusion errors were significantly associated with faster functional decline.
When integrated into the same model, cognitive challenge testing provided substantial added value. The inclusion of cognitive test measures explained up to 22.8% additional variance in the rate of functional decline compared to biomarkers alone. That study result reinforced the importance of early, individualized prediction.
Implications for Patients and Clinical Care
The study underscores the value of combining different diagnostic tools in early Alzheimer’s disease. Blood biomarkers offer a scalable, minimally invasive way to detect pathology. Cognitive challenge tests provide insight into how that pathology is affecting real-world daily functioning.
Together, these tools could enable clinicians to more accurately identify individuals at greatest risk of decline, monitor disease progression and tailor interventions earlier.
“The next step is to better understand how chronic conditions that are common in older adults influence the performance of blood biomarkers, with the goal of further improving diagnostic accuracy,” said Dr. Zheng.
The approach also has potential to improve clinical trial design by refining participant selection and providing more sensitive outcome measures, particularly in pre-dementia populations.
Advancing Alzheimer’s Research
Dr. Zheng’s study contributes to a growing body of work aimed at improving early detection and prognosis in Alzheimer’s disease. By combining biological and cognitive indicators, the research moves toward a more comprehensive, personalized model of disease monitoring that reflects both underlying pathology and functional impact.
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Tags: Alzheimer's disease, cognition, cognitive decline, dementia, Department of Psychiatry and Behavioral Sciences, Diane Zheng, Dr. David Loewenstein, Dr. Rosie Curiel Cid, Newsroom, Psychiatry and Behavioral Sciences