Age-Related Changes in Structure and Perfusion of Hippocampal Subfields and Connected Cortex

Poster No:

924 

Submission Type:

Abstract Submission 

Authors:

Yulin Ge1, Chenyang Li1, Jiaqi Wen1, Jiangyang Zhang2

Institutions:

1NYU Langone Health, New York, NY, 2NYU School of Medicine, New York, NY

First Author:

Yulin Ge  
NYU Langone Health
New York, NY

Co-Author(s):

Chenyang Li  
NYU Langone Health
New York, NY
Jiaqi Wen  
NYU Langone Health
New York, NY
Jiangyang Zhang  
NYU School of Medicine
New York, NY

Introduction:

As a primary structure affected by aging, the hippocampus and its subfields undergo tissue loss and diminished perfusion, which might contribute to cognitive decline and increased vulnerability to dementia. However, the relationship between hippocampus structure and vascular function remains unclear. Previous studies have demonstrated that the hippocampus connects with the prefrontal and entorhinal cortex through neural circuits, playing an essential role in cognitive processes [1]. Additionally, hormonal changes in older women may heighten their vulnerability to aging [2], emphasizing the need to investigate sex-specific patterns in the aging of these interconnected regions. Arterial spin labeling (ASL) can provide estimates of cerebral blood flow (CBF) and arterial transit time (ATT), serving as functional biomarkers that can detect early changes in vascular function [3]. In the current study, T1-weighted and ASL data from 540 subjects in the Human Connectome Project - Aging (HCP-Aging) dataset [4] were utilized to explore the relationship between structural and vascular functional alterations in the hippocampus subfield and connected prefrontal and entorhinal cortex, as well as their influence on cognition during healthy aging.

Methods:

The prefrontal and entorhinal cortex were segmented using the FreeSurfer pipeline based on T1-MPRAGE data. The segmentation of hippocampus subfields, including subiculum, CA1-4, and dentate gyrus was performed using Hippfold toolbox [5] (Fig. 1B). CBF and ATT in hippocampal subfields was unfolded and projected into the hippounfolded space to acquire subfield-specific values (Fig. 1D, E). For the ASL data, a multiple post-labeling delay (PLD) and a simultaneous multi-slice acquisition (SMS) pseudo-continuous ASL (pCASL) protocol were employed with the following parameters: labeling duration of 1500 ms, PLDs: 200 ms, 700ms, 1200ms, 1700ms, and 2200ms, each PLD was repeated 6, 6, 6, 10, and 15 times, respectively, and multiband factor of 6. The voxel size was 2.5mm isotropic with a total of 60 slices. The mb-PCASL data was preprocessed using hcpasl minimal processing pipeline (https://github.com/physimals/hcp-asl) to yield CBF and ATT maps (Fig. 1A, C). Total cognitive composite scores were used to reflect overall cognition. Statistical analysis was performed in GraphPad Prism and SPSS with p value < 0.05 as statistically significant.
Supporting Image: Figure1.jpg
 

Results:

As age increases, as shown in Figure 2, the volumes of the prefrontal cortex decrease, ATT delays, and CBF declines (Pfemale<0.05, Pmale<0.05); the entorhinal cortex only exhibits a decrease in volume (Pfemale<0.05, Pmale<0.05) and a decline in CBF in females (Pfemale=0.003). All hippocampal subfields show a decrease in volume and a delayed ATT with age (Pfemale<0.05, Pmale<0.05), whereas a decrease in CBF was not found in the subiculum (Pfemale=0.131, Pmale=0.177), and CA4 in males (Pmale=0.189) (Fig. 2). The volumes of the hippocampal subfields are negatively correlated with ATT (Pfemale<0.05, Pmale<0.05), except for subiculum (Pmale=0.091), CA1 (Pmale=0.053), and CA2 (Pmale=0.642) in males. The volumes of hippocampal subfields are positively correlated with CBF only in CA1 (Pfemale<0.001, Pmale=0.033), as well as CA3 (Pfemale=0.028) and DG (Pfemale=0.046) in females. Correlations among volumes, ATT, and CBF in the prefrontal and entorhinal cortex, hippocampus, and its subfields are more pronounced in females compared to males.
Supporting Image: Figure2.jpg
 

Conclusions:

Our study revealed the relationship between structure and vascular function in the hippocampus and connected prefrontal and entorhinal cortex, revealing sex- and subfield-specific trajectories with age. A deeper understanding of these relationships could offer deep insights into the mechanisms underlying age-related neurodegenerative diseases such as Alzheimer's.

Lifespan Development:

Aging 1

Modeling and Analysis Methods:

Image Registration and Computational Anatomy

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Cortical Anatomy and Brain Mapping
Cortical Cyto- and Myeloarchitecture

Physiology, Metabolism and Neurotransmission:

Cerebral Metabolism and Hemodynamics 2

Keywords:

Aging
Cerebral Blood Flow
Memory
MRI
NORMAL HUMAN
STRUCTURAL MRI

1|2Indicates the priority used for review

Abstract Information

By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.

I accept

The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:

I am submitting this abstract as an original work to be reproduced. I am available to be the “source party” in an upcoming team and consent to have this work listed on the OSSIG website. I agree to be contacted by OSSIG regarding the challenge and may share data used in this abstract with another team.

Please indicate below if your study was a "resting state" or "task-activation” study.

Other

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

Yes

Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.

Yes, I have IRB or AUCC approval

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Structural MRI

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

SPM
FSL
Free Surfer

Provide references using APA citation style.

1. Chu C.H. (2024) Overexpression of TIAM2S, a Critical Regulator for the Hippocampal-Medial Prefrontal Cortex Network, Progresses Age-Related Spatial Memory Impairment. Biological sciences and medical sciences, 79(11).
2. Torromino G. (2021). Estrogen-dependent hippocampal wiring as a risk factor for age-related dementia in women. Progress in neurobiology,197:101895.
3. Juttukonda M.R. (2021) Characterizing cerebral hemodynamics across the adult lifespan with arterial spin labeling MRI data from the Human Connectome Project-Aging. NeuroImage, 230:117807.
4. Bookheimer S.Y. (2019). The Lifespan Human Connectome Project in Aging: An overview. NeuroImage, 185:335-348.
5. Harms M.P. (2018). Extending the Human Connectome Project across ages: Imaging protocols for the Lifespan Development and Aging projects. NeuroImage, 183:972-984.

UNESCO Institute of Statistics and World Bank Waiver Form

I attest that I currently live, work, or study in a country on the UNESCO Institute of Statistics and World Bank List of Low and Middle Income Countries list provided.

No