Background: In preclinical Alzheimer’s disease (AD), early tau accumulation appears necessary for cognitive impairment. The early tau VOI metric is proposed to provide a PET regional estimate of tau accumulation that reflects post-mortem Braak stage 2. This study explored relationships between early tau VOI and cognition measured using the Cogstate Brief Battery (CBB) composite scores.
Methods: Data were drawn from the baseline visit of the A4 study for participants (n = 363, mean (SD) age = 72.0 (4.8) years, 58.1% female) that had data available for an 18-F flortaucipir PET scan and the CBB. Scores from the CBB learning/working memory (LWM) and psychomotor/attention (PSA) composites were expressed as z-scores using age-matched normative data. The early tau VOI comprised an average SUVr from the entorhinal, parahippocampal, fusiform, and inferior temporal regions, and participants were classified as tau positive based on the cut score of >1.1052 established previously. Analyses examined correlations between early tau VOI SUVr and each of the CBB composites and compared performance on the CBB composites between the tau positive and negative groups.
Results: SUVr for the early tau VOI was associated significantly with the LWM composite (Spearman’s ρ = -0.17, p = .001). On the LWM, the tau positive group (z = -0.42 [95% CI = -0.62, -0.23]) performed significantly worse than the tau negative group (z = -0.07 [95% CI = -0.16, 0.02], p <.001), as well as when compared to age-adjusted normative data. Performance of the tau negative group did not differ significantly from age-matched normative data for LWM. There were no significant relationships between early tau VOI and the PSA composite.
Conclusion: In preclinical AD, accumulation of tau in the regions comprising the early tau VOI is associated with subtle learning and working memory dysfunction but not with attentional functions. The specificity of this relationship indicates that the impact of tau accumulation of this region is specific to cognitive abilities that typically rely on medial temporal lobe function.