Verbal recognition declines in later Braak Stages compared to verbal delayed recall

Abstract Background Episodic memory decline is a hallmark of cognitive impairment due to Alzheimer’s Disease (AD). Literature has consistently indicated that delayed recall is compromised early in the disease. Recognition memory seems disrupted at late stages, although findings are mixed. Recent PET studies have demonstrated that the presence of tau in the medial temporal lobe (MTL) relates to early deterioration of delayed recall, but no PET studies have assessed how recognition memory relates to tau. We sought to investigate this relationship across the Braak staging continuum. Method Tau PET ([18F]‐MK6240) was acquired for 140 cognitively unimpaired elderly (CU), 54 MCI patients and 33 AD patients. Participants were segregated into Braak stages, based on in vivo PET neuroimaging of tau. Episodic memory was assessed using RAVLT delayed recall and recognition tests. MRI were segmented into probabilistic grey (GM) and white (WM) maps, non‐linearly registered to the ADNI template using Dartel and smoothed with an 8mm FWHM gaussian kernel. Independent samples t‐tests or their nonparametric counterparts were conducted to evaluate differences in memory scores by Braak stage. Voxel‐wise linear regression models were applied, using VoxelStats, with either delayed recall or recognition scores as dependent variables and tau PET as a predictor. Global amyloid, age, sex, education and APOE genotype were entered as covariates. Results Pairwise comparisons revealed that recognition memory is spared in early Braak stages. Voxel‐wise analyses in the whole sample unveiled that delayed recall and recognition memory relate to tau in virtually the same cortical areas. However, the strength of the relationships widely varied by memory type. Tau‐PET in anterior MTL and posterior hippocampus shows stronger associations with delayed recall, while tau binding in lateral temporal, temporooccipital and posterior areas exhibits stronger associations with recognition memory. Conclusion Our findings support the differentiation between delayed recall and recognition across the AD spectrum. Relationships between delayed recall and tau in the MTL are in concordance with previous research. Moreover, the contrast in the strength of the associations between memory and tau aggregation further supports the notion that delayed recall is already impaired in early Braak stages while recognition is damaged in later Braak stages.