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Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease
Douaud G, Menke RA, Gass A, Monsch AU, Rao A, Whitcher B, Zamboni G, Matthews PM et al.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013-01-01
Topic: Amyloid, tau and blood-test diagnosis
Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzheimer's disease (AD) no earlier than 2 years after baseline scanning, in order to focus on early, and hence more sensitive, imaging markers. We compared them to 22 stable amnestic MCI patients with similar cognitive performance and episodic memory impairment but who did not show progression of symptoms for at least 3 years. Significant group differences were mainly found in the volume and microstructure of the left hippocampus, while white matter group differences were also found in the body of the fornix, left fimbria, and superior longitudinal fasciculus (SLF). Diffusion index abnormalities in the SLF were the sign of a subtle microstructural injury not detected by standard atrophy measures in the corresponding gray matter regions. The microstructural measure obtained in the left hippocampus using diffusion imaging showed the most substantial differences between the two groups and was the best single predictor of future progression to AD. An optimal prediction model (91% accuracy, 85% sensitivity, 96% specificity) was obtained by combining MRI measures and CSF protein biomarkers. These results highlight the benefit of using the information of brain microstructural damage, in addition to traditional gray matter volume, to detect early, subtle abnormalities in MCI prior to clinical progression to probable AD and, in combination with CSF markers, to accurately predict such progression.
Key findings
- Significant group differences were mainly found in the volume and microstructure of the left hippocampus, while white matter group differences were also found in the body of the fornix, left fimbria, and superior longitudinal fasciculus (SLF).
- These results highlight the benefit of using the information of brain microstructural damage, in addition to traditional gray matter volume, to detect early, subtle abnormalities in MCI prior to clinical progression to probable AD and, in combination with CSF markers, to accurately predict such progression.
Why it matters
In this small study of 13 people with mild cognitive impairment who later progressed to Alzheimer's disease, diffusion imaging showed early microstructural abnormalities in the left hippocampus and other brain regions more than 2 years before clinical progression. This is about early detection using imaging, not about treating, curing, or preventing the disease.
Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 58/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 181 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.1 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 13.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Stephen M. Smith: h-index 148 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23365250) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1523/jneurosci.4437-12.2013
- PubMed: 23365250
- Original source →
- Free full text: Journal of Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Douaud, G., Menke, R. A., Gass, A., Monsch, A. U., Rao, A., Whitcher, B., et al. (2013). Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.4437-12.2013
Vancouver
Douaud G, Menke RA, Gass A, Monsch AU, Rao A, Whitcher B, et al. Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2013. doi:10.1523/jneurosci.4437-12.2013. PMID: 23365250.
BibTeX
@article{douaud2013-23365250,
author = {Douaud, G. and Menke, R. A. and Gass, A. and Monsch, A. U. and Rao, A. and Whitcher, B. and Zamboni, G. and Matthews, P. M. and others},
title = {{Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2013},
doi = {10.1523/jneurosci.4437-12.2013},
pmid = {23365250},
url = {https://doi.org/10.1523/jneurosci.4437-12.2013}
}
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