Early Alzheimer’s Biomarker Test Results Guide Clinical Care

Earlier disclosure of Alzheimer’s disease (AD) blood test results increased physicians’ diagnostic certainty and changed clinical management in patients evaluated for cognitive symptoms without raising patient anxiety or depression.Results of the first randomized trial to assess the clinical impact of these tests rather than diagnostic accuracy alone showed that disclosing plasma phosphorylated tau at threonine 217 (p-tau217) and neurofilament light chain (NfL) results at 3 months vs 9 months raised the proportion of patients with a very high-confidence (≥ 90%) etiologic diagnosis from 4.6% to 50%.Furthermore, physicians with early access to the results also initiated pharmacologic treatment more frequently (14% vs 5%) and planned more discharges to primary care (31% vs 12%).“The main take-home message is that the value of blood-based biomarkers goes beyond diagnostic accuracy,” study investigator Albert Puig-Pijoan, MD, PhD, Barcelona Brain Health Center, Hospital del Mar, Barcelona, Spain, told Medscape Medical News.“Having this information earlier in the diagnostic pathway can lead to earlier diagnostic certainty and earlier appropriate treatment, while also helping avoid unnecessary reassessments or prolonged specialist follow-up in some patients, without increasing psychological distress,” Puig-Pijoan added.The study was published online on October 5 in JAMA Neurology.From Diagnostic Accuracy to Clinical Utilityp-tau217 is highly accurate for identifying AD pathology, while NfL, although not specific for AD, may provide complementary information on neurodegeneration. In 2025, clinical practice guidelines supported the use of blood-based biomarkers in specialized care. However, evidence that these tests improve diagnostic certainty, management decisions, or other clinically relevant outcomes has remained limited.The goal of the PLASMAR trial was to address that gap. It included 220 patients undergoing evaluation for subjective cognitive decline, mild cognitive impairment (MCI), or mild dementia at a single memory clinic in Spain. Participants were randomly assigned to disclosure of plasma p-tau217 and NfL results at 3 months (n = 112) or 9 months (n = 108). Participants underwent standard diagnostic evaluation, including neurologic and neuropsychological assessment, structural imaging, and laboratory testing. Additional testing, including cerebrospinal fluid biomarkers or amyloid PET, could be ordered when clinically indicated.The median age of participants was 73 years, and 56% were women. At baseline, 46% had subjective cognitive decline, 31% had MCI, and 24% had mild dementia.At 3 months, 50.0% of patients in the early-disclosure group had a very high-confidence etiologic diagnosis — defined as at least 90% certainty — compared with just 4.6% of those whose biomarker results had not yet been disclosed (P < .001).After the delayed-disclosure group also received biomarker results, diagnostic certainty largely converged. At 9 months, 58.0% of the early-disclosure group and 52.8% of the delayed group had very high diagnostic certainty (P = .43). The increase in diagnostic certainty was observed across clinical syndromes at 3 months. By 9 months, the between-group difference had disappeared, except among those with MCI, in whom higher certainty persisted with earlier disclosure.The investigators said this may reflect the greater etiologic and prognostic uncertainty in MCI, where early biological information may have a sustained “anchoring effect” on clinical judgment.Earlier disclosure also prompted more diagnostic reclassification. At the 3-month visit, the etiologic diagnosis changed in 23.3% of patients in the early-disclosure group compared with 7.0% in the delayed-disclosure group (P = .002). Among those initially thought to have AD, diagnoses were reclassified in 30.6% vs 6.5%, respectively (P = .01). Clinical management changed as well. Earlier disclosure was associated with more frequent initiation of symptomatic AD treatment (14.3% vs 4.6%; P = .01), fewer planned follow-up neuropsychological reassessments for diagnostic clarification (30.4% vs 52.8%; P < .001), and more planned discharge from the memory clinic to primary care (31.3% vs 12.0%; P < .001).Puig-Pijoan described the finding as particularly significant for clinical practice, noting that earlier access to biomarker results could help clinicians identify patients who may benefit from timely treatment while sparing others unnecessary specialist follow-up. This approach could also provide patients with greater diagnostic certainty sooner and help memory clinics use their resources more efficiently. He added that the findings were “reassuring” regarding the psychological effects of disclosure.“Biomarker disclosure was not associated with increased anxiety or depressive symptoms or with worse quality of life. Perceived stress even showed a more favorable trajectory with earlier disclosure. Still, disclosure should be individualized, taking into account each patient’s clinical context, emotional state, and preferences,” he noted.An Important Step ForwardSheena Aurora, MD, vice president of medical affairs at the Alzheimer’s Association, who wasn’t involved in the study, said the randomized design strengthens the findings. “Earlier research showed that blood-based biomarkers can accurately detect Alzheimer’s pathology. This study takes an important step forward from asking, ‘How accurate are Alzheimer’s blood tests?’ to ‘Do they actually help patients and clinicians?’” she said.Aurora noted that the greater diagnostic confidence seen with earlier disclosure translated into clinical action, including earlier treatment decisions for patients likely to have AD and fewer repeat assessments and more planned discharge to primary care among those unlikely to have it.“This suggests Alzheimer’s blood biomarker tests can support earlier, more targeted clinical decision-making,” she said.Aurora cautioned that the tests are “not stand-alone diagnostics” and should be used as part of a comprehensive evaluation, with confirmatory testing for intermediate results. Larger, more diverse multicenter studies with longer follow-up and patient outcome data are still needed, she said.The study had no commercial funding. Disclosures for study authors are available with the original study publication. Aurora reported having no relevant disclosures.