Importance: It is important to determine the added clinical value for tau positron emission tomography (PET) in the diagnostic workup of patients with cognitive symptoms before widespread implementation in clinical practice.
Objective: To prospectively study the added clinical value of PET detecting tau pathology in Alzheimer disease (AD).
Design, setting, and participants: This prospective cohort study (Swedish BioFINDER-2 study) took place from May 2017 through September 2021. A total of 878 patients with cognitive complaints were referred to secondary memory clinics in southern Sweden and then recruited to the study. In total, 1269 consecutive participants were approached, but 391 did not meet inclusion criteria or did not complete the study.
Exposures: Participants underwent a baseline diagnostic workup, including clinical examination, medical history, cognitive testing, blood and cerebrospinal fluid sampling, magnetic resonance imaging of the brain, and a tau PET ([18F]RO948) scan.
Main outcomes and measures: The primary end points were change in diagnosis and change in AD drug therapy or other drug treatment between the pre- and post-PET visits. A secondary end point was the change in diagnostic certainty between the pre- and post-PET visits.
Results: A total of 878 participants with a mean age of 71.0 (SD, 8.5) years (491 male [56%]) were included. The tau PET result led to a change in diagnoses in 66 participants (7.5%) and a change in medication in 48 participants (5.5%). The study team found an association with overall increased diagnostic certainty after tau PET in the whole data set (from 6.9 [SD, 2.3] to 7.4 [SD, 2.4]; P < .001). The certainty was higher in participants with a pre-PET diagnosis of AD (from 7.6 [SD, 1.7] to 8.2 [SD, 2.0]; P < .001) and increased even further in participants with a tau PET positive result supporting an AD diagnosis (from 8.0 [SD, 1.4] to 9.0 [SD, 0.9]; P < .001). The association with tau PET results had the largest effect sizes in participants with pathological amyloid-β (Aβ) status, whereas no significant change in diagnoses was seen in participants with normal Aβ status.
Conclusions and relevance: The study team reported a significant change in diagnoses and patient medication when tau PET was added to an already extensive diagnostic workup that included cerebrospinal fluid AD biomarkers. Including tau PET was associated with a significant increase in certainty of underlying etiology. The effect sizes for certainty of etiology and diagnosis were largest in the Aβ-positive group and the study team suggests that clinical use of tau PET be limited to populations with biomarkers indicating Aβ positivity.