Joseph Hoepker Fernandes

The medial temporal lobe (MTL) is crucial for episodic memory. Tau pathology is a hallmark of Alzheimer's disease (AD) and accumulates in layer-specific patterns in the MTL during aging. It is, however, unclear whether early AD pathology relates to mesoscale network signatures distinct from non-pathological aging. To address this gap, we acquired 7 Tesla submillimeter-resolution resting-state fMRI, plasma-based AD biomarkers, glial fibrillary acidic protein (GFAP) levels, APOE genotype, regional [18F]PI-2620 tau PET burden, and longitudinal episodic memory data in 75 cognitively unimpaired older adults. Older age was associated with lower perirhinal-hippocampal connectivity and lower network segregation, whereas higher plasma-based AD pathology was associated with higher perirhinal-hippocampal connectivity. Furthermore, temporal-lobe tau burden was related to altered connectivity patterns in tau-vulnerable MTL subfields and layers, dependent on GFAP levels. Retrosplenial tau burden was associated with higher hippocampal-retrosplenial connectivity consistent with tau spread along canonical hippocampal output pathways. Finally, higher connectivity within the hippocampus attenuated the negative association between temporal-lobe tau burden and memory performance but predicted unfavorable memory trajectories. Our findings show differential associations of age and AD pathology with mesoscale MTL-connectivity patterns. Importantly, increased hippocampal connectivity may support memory function in the short term while contributing to subsequent memory decline.

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three‐layered architecture has been described in ex vivo investigations, the in vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. In this study, we used ultra‐high field structural MRI at 7 Tesla to investigate the depth‐dependent myelination patterns (measured by quantitative T1) of CA1 in younger adults, their relation to the local arterial architecture, and their association with individual differences in cognitive functions, specifically memory performance. Results show that left and right CA1 present depth‐dependent patterns of myelination, with the outer and inner compartments showing higher myelination than the middle compartment. No significant relationship between layer‐specific myelination of CA1 and distance to the nearest artery was observed. Right CA1 was found to be more myelinated than left CA1. Pairwise correlations and regression models showed that higher left CA1 myelination is linked to higher accuracy in object localization. Together, our data demonstrate the feasibility of describing the three‐layered myelin architecture of CA1 in vivo, and provide information on how alterations in the architecture of CA1 may relate to alterations in cognitive performance in younger adults.

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three-layered architecture has been described in ex-vivo investigations, the in-vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. In this study, we used ultra-high field structural MRI at 7 Tesla to investigate the depth-dependent myelination patterns (measured by quantitative T1) of CA1 in younger adults, their relation to the local arterial architecture, and their association with individual differences in cognitive functions, specifically memory performance. Results show that left and right CA1 present depth-dependent patterns of myelination, with the outer and inner compartments showing higher myelination than the middle compartment. No significant relationship between layer-specific myelination of CA1 and distance to the nearest artery was observed. Right CA1 was found to be more myelinated than left CA1. Pairwise correlations and regression models showed that higher left CA1 myelination is linked to higher accuracy in object localization. Together, our data demonstrates the feasibility of describing the three layered myelin architecture of CA1 in vivo, and provides information on how alterations in the architecture of CA1 may relate to alterations in cognitive performance in younger adults.