Earlier Disclosure of Blood-Based Biomarkers, Diagnostic Certainty, and Clinical Management: A Randomized Clinical Trial.

IMPORTANCE

Blood-based biomarkers show high performance for detecting Alzheimer disease (AD) pathology, but evidence on their impact on diagnostic certainty, clinical management, and emotional outcomes in routine care is limited.

OBJECTIVE

To determine whether earlier disclosure of plasma phosphorylated tau at threonine 217 (p-tau217) and neurofilament light chain (NfL) increases etiologic diagnostic certainty, influences clinical management, and affects emotional outcomes in individuals evaluated for cognitive symptoms.

DESIGN, SETTING, AND

PARTICIPANTS

This was a prospective randomized clinical trial conducted at a single memory clinic in Spain between February and October 2024, with 9 months of follow-up. Consecutive new outpatients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or mild dementia without a prior etiologic diagnosis were enrolled. Of 265 eligible participants, 220 were randomized to earlier disclosure of blood-based biomarkers at the 3-month visit or delayed disclosure at the 9-month visit.

INTERVENTION: Disclosure of blood-based biomarkers for AD pathology (p-tau217) and neurodegeneration (NfL) to the treating neurologist and participant, alongside standard clinical evaluation.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of participants achieving a very high-confidence etiologic diagnosis (≥90%). Secondary outcomes included changes in clinical management and emotional outcomes (anxiety, depression, perceived stress, and quality of life).

RESULTS

Among the 220 randomized participants (median [IQR] age, 73 [68-78] years; 123 [55.9%] women), baseline diagnoses were SCD (100 [45.5%]), MCI (68 [30.9%]), and mild dementia (52 [23.6%]). At 3 months, a very high-confidence etiologic diagnosis was achieved in 56 of 112 participants in the earlier-disclosure arm (50.0%) compared with 5 of 108 in the delayed-disclosure arm (4.6%) (P < .001). Diagnostic certainty converged after disclosure in both arms, except among participants with MCI, in whom higher certainty persisted in the earlier-disclosure arm. Earlier disclosure was associated with more frequent initiation of symptomatic AD treatment (16/112 [14.3%] vs 5/108 [4.6%]; difference, 9.7; 95% CI, 1.8 to 17.8; P = .01), fewer planned follow-up neuropsychological reassessments for diagnostic clarification (34/112 [30.4%] vs 57/108 [52.8%]; difference, -22.4; 95% CI, -34.4 to -9.4; P < .001), and more planned discharge from the memory clinic to primary care (35/112 [31.3%] vs 13/108 [12.0%]; difference, 19.2; 95% CI, 8.4 to 29.5; P < .001). Earlier disclosure was not associated with worse emotional outcomes.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, earlier disclosure of blood-based biomarkers increased etiologic diagnostic certainty and led to earlier, targeted clinical management without increasing emotional distress. These findings support the integration of blood-based biomarkers into memory clinic diagnostic pathways.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06246019.