Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer's disease
Open accessAbstract
There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer's disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging data [including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA) and radial diffusivity (DR)] and volumetric comparisons of medial temporal lobe (MTL) structures were conducted. Results indicated equivalent entorhinal cortex and hippocampal volumes between risk groups. Nevertheless, the high risk group showed decreased microstructural integrity in WM tracts with direct and secondary connections to the MTL. The predominant alteration in WM integrity in the high AD-risk group was decreased FA not solely driven by either DA or DR changes alone in regions where no MD changes were observed. A second pattern observed in a smaller number of regions involved decreased FA and increased DR. These results suggest that disconnection of MTL-neocortical fiber pathways represents a very early event in the course of AD and suggest that demyelination may represent one contributing mechanism.
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Reduced myelin volume and integrity often occur prior to the onset of dementia and are predictive of future cognitive impairment.
“Reduced myelin volume and integrity often occur prior to the onset of dementia and are predictive of future cognitive impairment23,24,33,36.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [36]
The Discussion (page unavailable) reports reduced white-matter integrity in cognitively normal women at high risk for Alzheimer’s disease and says the imaging pattern is consistent with early myelin loss. It does not establish reduced myelin volume or show that these changes predict future cognitive impairment; the authors say longitudinal follow-up is needed to test prediction. (LLM, conf=0.87)
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References 59 · Cited by 112
- Authors
- Gold, B. T., Powell, D. K., Andersen, A. H., & Smith, C. D.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Gold, Brian T.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 52
- Issue
- 4
- Pages
- 1487-1494
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC2910213
- OpenAlex
- W2111848002
- Cited by
- 112
- References
- 59
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 3 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 11 · 2015: 12 · 2014: 11 · 2013: 10 · 2012: 18
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UKnowledge (University of Kentucky) (submittedVersion, cc-by-nc-nd)
- ScholarWorks@UMassAmherst (University of Massachusetts Amherst) (submittedVersion)
- Funders
- NINDS (R01 NS-36660)
- NIA (R01 AG033036)
- NSF (BCS-0814302)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, preclinical Alzheimer's disease, white matter microstructure, white matter integrity, APOE ε4, family history of dementia, women, fractional anisotropy, radial diffusivity, axial diffusivity, mean diffusivity, entorhinal cortex, hippocampus, medial temporal lobe, demyelination, white matter disconnection
- MeSH terms
- Aged, Alzheimer Disease, Brain, Female, Humans, Middle Aged, Nerve Fibers, Myelinated, Prognosis, Reference Values, Risk Factors, Diffusion Magnetic Resonance Imaging
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