Factors associated with discordant visual and quantitative amyloid PET results

Factors underlying discordant visual and quantitative amyloid beta-positron emission tomography (Aβ-PET) results and their clinical implications are not well understood.

Participants from the 1Florida Alzheimer's Disease Research Center (1FLADRC) underwent Aβ-PET, blood draw, brain magnetic resonance imaging (MRI), and neuropsychological testing. We evaluated differences in demographics, apolipoprotein E (APOE) status, biomarkers, and cognition among older adults with concordant and discordant visual-quantitative Aβ-PET. Discordance was defined as positive visual read (V) of Aβ-PET with below-threshold Centiloid quantification (Q; CL <25; V+/Q-) or negative visual read with CL ≥25 (V-/Q+).

We studied 386 participants (mean age ± SD: 70.7 ± 7.8, 55.2% female, 44.6% Hispanic White). Compared to V+/Q-, V-/Q+ had a higher frequency of APOE ε4 carriers (40%). Black/African American participants were overrepresented in V-/Q+ (40.9%). Both discordant groups had higher plasma phosphorylated tau 217 (p-tau217) and glial fibrillary acidic protein (GFAP) than V-/Q- but lower than V+/Q+. Discordant groups had greater gray matter volume and better cognitive performance than V+/Q+.

Discordant Aβ-PET findings likely hold clinical significance and may reflect early stages of neuropathological progression.

Groups with concordant/discordant visual-quantitative amyloid beta-positron emission tomography (Aβ-PET) results were compared.Visual-/quant+ were more likely than visual+/quant- to be apolipoprotein E (APOE) ε4 carriers and Black/African American.Discordant groups had higher plasma phosphorylated tau 217 (p-tau217) and glial fibrillary acidic protein (GFAP) than concordant negative.Discordant groups had less atrophy and better cognition than concordant positive.Centiloid quantification should supplement visual reads in clinical settings.