Microstructural white matter changes in cognitively normal individuals at risk of amnestic MCI
Abstract
OBJECTIVE: Since Alzheimer disease (AD) is a slowly progressive disorder and its pathologic features are likely to be present for many years before symptoms become manifest, we investigated whether microstructural white matter changes similar to those identified in patients with AD can be detected in cognitively normal individuals without dementia destined to develop amnestic mild cognitive impairment (aMCI). METHODS: We studied 193 cognitively normal individuals, of whom 173 remained cognitively stable (CN-stable) and 20 were diagnosed with aMCI (CN-aMCI converter) 2 years later. Structural MRI and diffusion tensor imaging were acquired at baseline to assess gray matter atrophy and microstructural white matter changes, respectively. RESULTS: At baseline, compared with CN-stable, CN-aMCI converters had substantial reductions in white matter integrity in the precuneus, parahippocampal cingulum, parahippocampal gyrus white matter, and fornix. Other diffuse white matter changes were observed in the frontal, parietal, and subcortical regions, whereas gray matter structures were relatively intact. The fractional anisotropy (FA) values of the precuneus were found to be a predictor of conversion from cognitively normal to aMCI. In addition, the FA values of the left parahippocampal gyrus white matter were predictive of subsequent episodic memory decline. CONCLUSIONS: Microstructural white matter changes are present in cognitively normal individuals in the pre-aMCI stage, and may serve as a potential imaging marker of early AD-related brain changes.
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Previous neuroimaging and post-mortem brain studies have observed white matter alterations in the presence of minimal or only weak grey matter atrophy, suggesting that in principle white matter alterations in Alzheimer's disease are not dependent on grey matter atrophy.
“However, previous neuroimaging as well as post-mortem brain studies have observed white matter alterations in the presence of minimal or only weak grey matter atrophy (de la Monte, 1989; Zhuang et al., 2012), suggesting that in principle white matter alterations in Alzheimer’s disease are not dependent on grey matter atrophy.”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Zhuang et al., 2012
The current results are consistent with previous studies reporting that decreased fibre tract integrity in posterior parietal and medial temporal white matter is associated with imminent conversion from asymptomatic cognitive status to mild cognitive impairment within 2 years or with abnormal CSF amyloid and neuroinjury markers.
“The current results are consistent with previous studies on presumed preclinical Alzheimer’s disease, reporting decreased fibre tract integrity within the posterior parietal white matter and medial temporal white matter to be associated with imminent conversion from asymptomatic cognitive status to mild cognitive impairment within 2 years (Zhuang et al., 2012) or with the presence of both abnormal”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Zhuang et al., 2012
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- Authors
- Zhuang, L., Sachdev, P. S., Trollor, J. N., Kochan, N. A., Reppermund, S., Brodaty, H., & Wen, W.
- Affiliations
- UNSW Sydney (AU)
- ORCID
- Venue
- Neurology
- Published
- 2012-08-21
- Volume
- 79
- Issue
- 8
- Pages
- 748-754
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2154158168
- Cited by
- 125
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 11 · 2019: 6 · 2018: 13 · 2017: 10 · 2016: 15 · 2015: 8 · 2014: 12 · 2013: 14 · 2012: 5
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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
- amnestic mild cognitive impairment, Alzheimer's disease, white matter microstructure, fractional anisotropy, precuneus, fornix, episodic memory decline, cognitively normal individuals
- MeSH terms
- Aged, Aged, 80 and over, Amnesia, Atrophy, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Predictive Value of Tests, Geriatric Assessment, Anisotropy, Nerve Fibers, Unmyelinated, Early Diagnosis, Diffusion Tensor Imaging, Neuroimaging, Cognitive Dysfunction
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