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Updated: May 31, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Using diffusion tensor imaging and mixed-effects models to investigate primary and secondary white matter
Laurence O'Dwyer1, Franck Lamberton, Arun L W Bokde
1Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany. larodwyer@gmail.com
Abstract:
White matter (WM) degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI) may be a key indicator of early damage in AD. Here, we analyzed WM diffusion tensor data using Tract-Based Spatial Statistics in conjunction with mixed-effects models. Four indices of diffusion were assessed in 61 healthy control, 19 non-amnestic MCIs, 14 amnestic MCIs, and 9 AD patients. The aim of the study was to use advanced mixed-effects models to investigate the retrogenesis hypothesis of AD, which suggests that tracts that are late to myelinate in ontogenetic development are the earliest to be affected in AD. Our results show that a number of late-myelinating pathways, including the parahippocampal region and the inferior longitudinal fasciculus, were predominantly affected by changes in WM volume. Conversely, early-myelinating pathways were found to be affected by a combination of both WM and gray matter (GM) atrophy. A model of the entire WM structure of the brain returned GM models for two indices of diffusion, suggesting that more complex regional landscapes of diffusion lie hidden beneath a global analysis of the entire brain. Our results warn against an explanation of white matter damage that points simply to one of two mechanisms: secondary degeneration or direct damage of myelin. We suggest that tracts may be affected by both mechanisms, with the balance depending on whether tracts are early or late-myelinating. A greater understanding of the pattern of WM changes in AD may prove useful for the early detection of AD.
Insights
White matter degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is linked to myelination timing. Late-myelinating tracts show volume changes, while early-myelinating tracts show atrophy, suggesting complex damage mechanisms.
Area of Science:
- Neuroscience
- Neuropathology
- Medical Imaging
Background:
- White matter (WM) degeneration is an early indicator in Alzheimer's disease (AD) and mild cognitive impairment (MCI).
- The retrogenesis hypothesis proposes that WM tracts affected earliest in AD are those that myelinate latest during development.
Purpose of the Study:
- To investigate the retrogenesis hypothesis in AD and MCI using advanced statistical models.
- To analyze diffusion tensor imaging (DTI) data to understand WM changes in relation to myelination timing.
Main Methods:
- Tract-Based Spatial Statistics (TBSS) applied to DTI data from 61 healthy controls, 19 non-amnestic MCIs, 14 amnestic MCIs, and 9 AD patients.
- Mixed-effects models used to assess four diffusion indices and their relationship with WM volume and gray matter (GM) atrophy.
- Analysis of both specific pathways and the entire WM structure.
Main Results:
- Late-myelinating pathways (e.g., parahippocampal region, inferior longitudinal fasciculus) showed predominant WM volume changes.
- Early-myelinating pathways were affected by a combination of WM and GM atrophy.
- Global WM analysis revealed complex regional diffusion patterns, with GM models influencing two diffusion indices.
Conclusions:
- WM changes in AD and MCI are not solely explained by secondary degeneration or direct myelin damage.
- The balance of damage mechanisms (secondary degeneration vs. direct myelin damage) depends on whether WM tracts are early or late-myelinating.
- Understanding these patterns can aid in the early detection of AD.
