Association of hippocampal atrophy with tau pathology of temporal regions in preclinical Alzheimer's disease.

Abstract

Background: Hippocampal atrophy is linked to memory and cognitive deficits, preceding clinical diagnosis of mild cognitive impairment (MCI) by decades. Morphometry changes in the hippocampal formation (HF) and their relationship to tau deposition in non-demented individuals remains unclear.

Objective: To investigate morphometry changes in the HF and their association with tau deposition in a non-demented cohort.

Methods: Eighty-three subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent T1-weighted MRI and Tau-PET scans at baseline and longitudinal follow-up. Participants were divided into amyloid-negative (Aβ-) and amyloid-positive (Aβ+) groups. Hippocampal volume/thickness were measured, and associations with tau deposition in temporal regions were examined using multivariable linear regression.

Results: No significant association was found between the hippocampal volume/thickness and tau deposition of temporal regions for the Aβ- group. For the Aβ+ group, the hippocampal thickness was significantly associated with tau deposition of entorhinal cortex (ERC) for both hemispheres, and temporal pole, inferior temporal, and middle temporal regions for right hippocampi with the longitudinal follow up scans, while no significant association with the baseline scans. It was interesting that there was strong association between the baseline tau deposition of ERC and temporal pole and the longitudinal follow up thickness of left hippocampi, while the associated regions for the right hemisphere were ERC, temporal pole, and inferior temporal regions.

Conclusions: Hippocampal atrophy may precede cognitive symptoms, with tau deposition in adjacent temporal regions contributing to hippocampal changes. The right HF appears more vulnerable than the left, indicating hemispheric differences in pathology.