Quantitative MRI of the hippocampus reveals microstructural trajectories of aging and Alzheimer's disease pathology
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Alfie Wearn1, Christine L Tardif1,2, Ilana R Leppert2
1Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
Abstract:
Hippocampal degeneration is a feature of both normal aging and Alzheimer's disease (AD). Prior to macroscopic degeneration, microstructural changes occur such as demyelination, iron deposition, or subtle atrophy, which can be characterized in vivo using MRI. We topographically mapped measures of microstructure and macrostructure across the unfolded surface of the hippocampus in 224 healthy older adults at risk for AD (aged 57 to 87) and 37 younger adults (aged 18 to 37). We describe three spatial regions of unique structural covariance between four parameters sensitive to microstructural tissue properties (R1, MTsat, R2*, PD) and macrostructure (surface thickness), with high convergence with previous spatial segmentations. We demonstrate both cross-sectional and longitudinal associations of microstructure with healthy aging across the lifespan, AD pathological hallmarks, genetic risk, and cognition. These associations had subtle variations across different spatial areas of the hippocampus. We report associations between age and qMRI measures sensitive to macromolecular concentration (R1, MTsat) and paramagnetic susceptibility (R2*), consistent with mechanisms of demyelination and increased iron deposition as key hallmarks of the aging hippocampus and in presymptomatic stages of AD. qMRI measures did not explain more variance in delayed recall than global PET measures, suggesting variation in cognitive performance in aging and incipient AD is influenced by factors beyond hippocampal microstructure. We demonstrate the utility of quantitative MRI to provide greater insight into hippocampal health compared to typical macrostructural measures through "in vivo histology," opening a window to understanding neuropathological mechanisms in the earliest stages of age- and disease-related neurodegeneration.
Insights
Quantitative MRI reveals microstructural changes in the aging hippocampus, offering insights into early Alzheimer's disease (AD) and cognitive decline beyond macrostructural measures.
Area of Science:
- Neuroimaging
- Neuroscience
- Biomedical Engineering
Background:
- Hippocampal degeneration is a hallmark of normal aging and Alzheimer's disease (AD).
- Microstructural changes like demyelination and iron deposition precede macroscopic degeneration and can be detected using MRI.
- Understanding these early changes is crucial for diagnosing and managing age-related cognitive decline.
Purpose of the Study:
- To topographically map hippocampal microstructure and macrostructure in healthy older adults at risk for AD and younger adults.
- To identify spatial regions of structural covariance between microstructural and macrostructural measures.
- To investigate associations between hippocampal microstructure, aging, AD pathology, genetic risk, and cognition.
Main Methods:
- Quantitative MRI (qMRI) was used to measure microstructural parameters (R1, MTsat, R2*, PD) and macrostructure (surface thickness) across the unfolded hippocampus.
- The study included 224 healthy older adults (57-87 years) at risk for AD and 37 younger adults (18-37 years).
- Associations between qMRI measures and aging, AD hallmarks, genetic risk, and cognitive performance (delayed recall) were analyzed.
Main Results:
- Three distinct spatial regions of structural covariance were identified within the hippocampus.
- Age-related changes in qMRI measures (R1, MTsat, R2*) were consistent with demyelination and increased iron deposition, characteristic of aging and early AD.
- Hippocampal microstructure measures did not explain more variance in delayed recall than global PET measures, indicating other factors influence cognition.
Conclusions:
- Quantitative MRI provides an "in vivo histology" approach to better understand hippocampal health and early neurodegeneration compared to macrostructural measures alone.
- Microstructural changes in the hippocampus are associated with healthy aging, AD risk, and cognitive function.
- Further research is needed to explore factors beyond hippocampal microstructure influencing cognitive performance in aging and AD.
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