CORTICAL TAU DEPOSITION FOLLOWS PATTERNS OF ENTORHINAL FUNCTIONAL CONNECTIVITY IN COGNITIVELY NORMAL OLDER ADULTS

Abstract

thickness. Global PiB DVR and partial volume corrected FTP SUVR values were calculated for entorhinal (ERC) and inferior temporal cortex (IT). Cognitive performance was measured using domain-specific (episodic memory, working memory, executive function) and general cognition scores. Structural covariance of the BF ROIs was assessed using second-level VBM, and functional connectivity was assessed between BF ROIs and the rest of the brain. Results: BF volumes were negatively correlated with FTP in ERC (Ch4: r1⁄4-0.46, p1⁄40.002; Fig.1) and IT in PiB+ individuals. Also in PiB+ participants, BF volumes were related to episodic memory, executive function and general cognition (Ch1-3: r1⁄40.48, p1⁄40.003; Fig.2). Age (r>0.43, p<0.001), hippocampal volume (r>0.6, p<0.001; Fig.3A&C) and ERC thickness (r>0.26, p<0.01; Fig.3B&D) also correlated with BF volumes. Despite this, BF-cognition relationships remained significant even when adjusting for age, sex and hippocampal volume. Functional connectivity and structural covariance analyses revealed unique patterns of association of Ch1-3 and Ch4 ROIs to limbic and paralimbic networks, systems affected by AD pathology accumulation (Fig.4) Conclusions: Associations between BF structure and MTL tau pathology in cognitively normal adults may indicate an early pathological link between two AD vulnerable brain regions. In line with this, the associations between MTL tau and BF volume were driven by amyloid positive individuals. BF structure was related to general cognition in amyloid positive participants, demonstrating that BF volume provides unique information that is not captured by hippocampal volume.