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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

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Microstructural Changes in Aging Hippocampal Pathways: Insights From the HCP-Aging Diffusion MRI Study.

Huize Pang¹, Zhe Sun¹, Zifei Liang¹

¹Department of Radiology, NYU Grossman School of Medicine, New York, New York, USA.

Human Brain Mapping

|September 23, 2025

Summary

This summary is machine-generated.

This study reveals age-related microstructural changes in brain pathways connecting the hippocampus to cortical regions in healthy adults. Mean diffusivity (MD) was the most sensitive indicator of aging, with significant alterations observed in the prefrontal and occipital pathways.

Keywords:

aging diffusion characteristics hippocampal connectivity human connectome project microstructural degeneration

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Area of Science:

Neuroimaging
Aging Research
Cognitive Neuroscience

Background:

Alzheimer's disease is linked to hippocampal atrophy.
Limited research exists on hippocampal pathway microstructural integrity in healthy aging.
Understanding these changes is crucial for identifying early markers of neurodegeneration.

Purpose of the Study:

To investigate age-related changes in the microstructural integrity of hippocampal pathways in healthy adults.
To examine the relationship between age, cognition, and diffusion metrics in these pathways.
To establish normative references for healthy aging of hippocampal-cortical connectivity.

Main Methods:

Analysis of 475 healthy individuals (aged 36-90) from the Human Connectome Project Aging (HCP-A) dataset.
Extraction and characterization of hippocampal fiber pathways (Papez, Prefrontal, Occipital, Parietal) using diffusion MRI metrics (FA, MD, NDI, ODI).
Application of partial linear and quadratic nonlinear correlation analyses, adjusted for hippocampal volumes.

Main Results:

Fractional anisotropy (FA), mean diffusivity (MD), and orientation distribution index (ODI) showed linear age-related changes; neurite density index (NDI) showed quadratic changes.
Mean diffusivity (MD) emerged as the most age-sensitive parameter.
The Prefrontal and Occipital pathways exhibited the most pronounced age-related microstructural alterations, with sex-specific differences noted in the Parietal and Occipital pathways.
Cognitive decline was associated with microstructural changes in the Occipital and Prefrontal pathways, particularly in females.

Conclusions:

This study provides novel insights into age- and cognition-related microstructural changes in hippocampal pathways across the adult lifespan.
Findings offer normative data for healthy aging of brain connectivity.
These results have potential implications for understanding and detecting early changes related to Alzheimer's disease and other dementias.