Hemispheric lateralization of Tau associations with visual and verbal memory in Alzheimer’s disease

Abstract Purpose Alzheimer’s disease affects the brain in complex ways, and the location of tau tangles may influence specific types of memory problems. In this study, we examined how tau accumulation relates to verbal and visual memory performance, and whether these associations show a preference for one hemisphere of the brain over the other. Methods We administered the Rey Auditory Verbal Learning Test (RAVLT) and its nonverbal analog, the Aggie Figures Learning Test (AFLT), to 132 cognitively unimpaired elderly participants and 44 cognitively impaired, amyloid-positive individuals from the Translational Biomarkers in Aging and Dementia cohort. All participants underwent 18 FMK6240 tau PET, 18 FAZD4694 amyloid PET, and structural MRI scans. We analyzed the data using region-of-interest and voxel-wise regression models, as well as correlation analyses. Results Voxel-wise analyses showed that higher tau load in the right hemisphere was associated with worse visual memory, confirming a lateralized relationship. Left-hemisphere tau associations with verbal memory were observed at higher t-values. In regression models including both memory scores, visual memory remained significantly associated with tau on the right hemisphere ( β AFLT~Rtau =-0.22, p =0.001; β RAVLT~Rtau =-0.1, p =0.13), whereas both visual and verbal memory remained significant on the left hemisphere ( β AFLT~Ltau =-0.16, p =0.03; β RAVLT~Ltau =-0.14, p =0.04). These patterns were also reflected in Braak regions, except for Braak I, where only left tau–verbal and right tau–visual associations remained significant. Conclusion Our findings support lateralized associations between tau accumulation and memory deficits, with visual memory linked to right-hemisphere tau and verbal memory to left-hemisphere tau. This pattern is consistent with lateralization of memory functions observed in other neurological conditions and highlights the importance of considering hemisphere-specific tau pathology in Alzheimer’s disease.