A Blood Test Could Help Transform the Alzheimer’s Diagnostic Pathway

For older adults experiencing cognitive changes, reaching an accurate Alzheimer’s disease diagnosis can be a lengthy and complex process. A new Cleveland Clinic study is examining whether blood-based biomarkers (BBMs) can help make that pathway more reliable and efficient — potentially enabling earlier identification and more timely treatment.

“Mild cognitive impairment and dementia are frequently missed or underdiagnosed in primary care settings, where many patients first present with symptoms like memory loss and changes in behavior,” explains Cleveland Clinic geriatrician Saket Saxena, MD, the study's principal investigator. “Our goal is to help determine how health systems can improve the real-world care of older adults by moving BBM testing from the bench to the bedside.”

He notes that an ongoing shortage of geriatricians and neurologists can further delay access to specialty evaluations, making it particularly important to identify which patients are most likely to benefit from a referral.

Addressing diagnostic gaps

Nearly a decade ago, Cleveland Clinic established a systematic approach to identifying cognitive impairment in its primary care facilities. During annual wellness visits, eligible patients are screened using the Mini-Cog instrument, a three-item recall test that includes a clock-drawing component. Those with concerning results may then be referred to geriatric specialists or the Center for Brain Health for further evaluation.

Although approximately 3,000 Mini-Cog tests are performed each month, the protocol does not clearly establish which patients warrant specialized care or when confirmatory testing should be pursued. Dr. Saxena says the study is intended to help address those gaps by evaluating how BBM testing could be used to guide referrals and subsequent diagnostic decisions.

He notes that BBMs may offer several potential advantages over currently available methods for identifying Alzheimer’s pathology. Compared with cerebrospinal fluid testing and brain positron emission tomography (PET), blood tests are minimally invasive and require less specialized equipment and personnel for sample collection.

Study specifics

The study will focus on the Elecsys Phospho-Tau (217P) Plasma BBM, which measures phosphorylated tau 217 (pTau-217) in plasma. A second biomarker, pTau-181, will also be measured for secondary analysis.

The pTau-217 test is intended to be used as a triage tool to help clinicians determine whether a patient is more or less likely to have the amyloid plaque or tau neurofibrillary tangle pathology associated with Alzheimer’s disease.

Geriatrician and study coinvestigator Hiba Khan, MD, emphasizes that the test is not intended to replace a comprehensive clinical evaluation or confirmatory studies. Cerebrospinal fluid or PET testing will still be required before disease-modifying treatments, including anti-amyloid monoclonal antibody infusions, are initiated.

“That distinction is particularly important as clinicians begin incorporating emerging biomarkers into practice,” she adds. “BBM results should always be interpreted alongside other clinical tests and the patient’s broader clinical concerns.”

The observational-implementation study will follow patients through the diagnostic process, beginning when primary care identifies suspected cognitive impairment. Investigators will examine whether incorporating BBM testing affects referrals, diagnostic accuracy and healthcare resource utilization.

Researchers, who plan to enroll as many as 1,800 participants, will evaluate factors such as referral patterns, time between diagnostic milestones, the resources required to confirm the diagnosis and total cost of care.

Looking ahead

Dr. Saxena and his team hope the findings will contribute to a broader effort involving multiple U.S. and international health systems, including those with limited resources. Ultimately, the study reflects a shift in thinking about dementia in older adults, he explains.

“Innovation is not simply about developing a promising test; it also requires us to determine how screening tools can be integrated thoughtfully into clinical care,” Dr. Saxena says. “By studying the workflows, referral patterns and clinical decision-making surrounding pTau-217 testing, we hope to generate evidence that can help shape the next generation of Alzheimer’s care.”