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

Introduction: The accumulation of neurofibrillary tau tangles, a neuropathological hallmark of Alzheimer's disease (AD), occurs in medial temporal lobe (MTL) regions early in the disease process, with some of the earliest deposits localized to subregions of the entorhinal cortex. Although functional specialization of entorhinal cortex subregions has been reported, few studies have considered functional associations with localized tau accumulation.

Methods: In this study, stepwise linear regressions were used to examine the contributions of regional tau burden in specific MTL subregions, as measured by ¹⁸F-MK6240 PET, to individual variability in cognition. Dependent measures of interest included the Clinical Dementia Rating Sum of Boxes (CDR-SB), Mini Mental State Examination (MMSE), and composite scores of delayed episodic memory and language. Other model variables included age, sex, education, APOE4 status, and global amyloid burden, indexed by ¹¹C-PiB.

Results: Tau burden in right Brodmann area 35 (BA35), left and right Brodmann area 36 (BA36), and age each uniquely contributed to the proportion of explained variance in CDR-SB scores, while right BA36 and age were also significant predictors of MMSE scores, and right BA36 was significantly associated with delayed episodic memory performance. Tau burden in both left and right BA36, along with education, uniquely contributed to the proportion of explained variance in language composite scores. Importantly, the addition of more inclusive ROIs, encompassing less granular segmentation of the entorhinal cortex, did not significantly contribute to explained variance in cognition across any of the models.

Discussion: These findings suggest that the ability to quantify tau burden in more refined MTL subregions may better account for individual differences in cognition, which may improve the identification of non-demented older adults who are on a trajectory of decline due to AD.