Tau PET accumulation in Brodmann areas 35 and 36 is associated with individual differences in cognition in non‐demented older adults

Abstract

AbstractBackgroundMounting evidence indicates that tau accumulation in the entorhinal cortex (EC) occurs early in the course of Alzheimer’s disease (AD). Recent advances in automated segmentation methods allow for the investigation of smaller regions of the medial temporal lobes (MTL), including subregions of the EC. This study examined tau deposition in relation to individual differences in cognition among older adults, assessing whether MTL subregions explained a greater proportion of variance in cognition, when compared to standard labeling methods.MethodAnalyses included 91 BIOCARD study participants who were cognitively unimpaired (CU; n = 82) or had mild cognitive impairment (MCI; n = 9). Stepwise linear regressions were used to examine the contributions of regional tau burden to individual differences in the CDR sum of boxes (CDR‐SB), MMSE, and composite scores of global cognition and memory. Other model variables included amyloid burden, APOE4 status, sex, and education. Amyloid burden was assessed by 11C‐PiB and regional tau was assessed by 18F‐MK‐6240 PET. SUVR values representing tau accumulation were extracted using two MRI segmentation methods: (1) the FreeSurfer‐derived EC label, and (2) Automatic Segmentation of Hippocampal Subfields (ASHS)‐derived MTL subregions, including the EC and Brodmann areas 35 and 36 (Br35, Br36) defined in 1mm‐MNI space. Partial volume correction was applied to the motion‐corrected PET data.ResultTau burden in the right Br35, right Br36, and age were significant predictors of CDR‐SB scores, with the greatest proportion of variance explained when all three were included. The FreeSurfer‐labeled EC and other variables did not significantly contribute to the model. Right Br36 and age were significant predictors of MMSE while right Br36 and APOE4 status were significant predictors of the global cognition composite score, and right Br36 was a significant predictor of the memory composite score. Follow‐up analyses showed that addition of the FreeSurfer EC region did not significantly contribute to any of the models.ConclusionQuantifying tau burden in Br35 and Br36 better accounted for individual variability in cognition, when compared to standard EC labeling approaches. This suggests tau burden in these subregions may help identify CU and MCI individuals who are on a trajectory of decline due to AD.