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Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration
Weston PS, Simpson IJ, Ryan NS, Ourselin S, Fox NC.. Alzheimer's research & therapy, 2015-07-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is recognized to have a long presymptomatic period, during which there is progressive accumulation of molecular pathology, followed by inexorable neuronal damage. The ability to identify presymptomatic individuals with evidence of neurodegenerative change, to stage their disease, and to track progressive changes will be important for early diagnosis and for prevention trials. Despite recent advances, particularly in magnetic resonance imaging, our ability to identify early neurodegenerative changes reliably is limited. The development of diffusion-weighted magnetic resonance imaging, which is sensitive to microstructural changes not visible with conventional volumetric techniques, has led to a number of diffusion imaging studies in AD; these have largely focused on white matter changes. However, in AD cerebral grey matter is affected very early, with pathological studies suggesting that grey matter changes predate those in white matter. In this article we review the growing number of studies that assess grey matter diffusivity changes in AD. Although use of the technique is still at a relatively early stage, results so far have been promising. Initial studies identified changes in diffusion measures in the hippocampi of patients with mild cognitive impairment, which predated macroscopic volume loss, with positive predictive value for progression to AD dementia. More recent studies have identified abnormalities in multiple neocortical areas (particularly the posterior cingulate) at various stages of disease progression. Studies of patients who carry genetic mutations predisposing to autosomal dominant familial AD have shown cortical and subcortical grey matter diffusivity changes several years before the expected onset of the first clinical symptoms. The technique is not without potential methodological difficulties, especially relating to partial volume effects, although recent advances appear to be reducing such issues. Going forward, further utilization of grey matter diffusion measurements in AD may improve our understanding with regards to the timing and nature of the earliest presymptomatic neurodegenerative changes. This imaging technique may also be useful in comparing and contrasting subtle variations in different disease subgroups, and as a sensitive outcome measure for presymptomatic clinical trials in AD and other neurodegenerative diseases.
Key findings
- However, in AD cerebral grey matter is affected very early, with pathological studies suggesting that grey matter changes predate those in white matter.
- Although use of the technique is still at a relatively early stage, results so far have been promising.
Why it matters
This review describes diffusion imaging as a promising but still early method for detecting grey matter changes in Alzheimer's disease before visible shrinkage. It is about early diagnosis and tracking, not about treating or preventing the disease.
Study details
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, 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 (Alzheimer's research & therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — 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 214 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 3 / 6 | Cited 7.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 3 / 4 | Cited 85 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Nick C. Fox: h-index 173 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26136857) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13195-015-0132-3
- PubMed: 26136857
- Original source →
- Free full text: Alzheimer s Research & Therapy →
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. Check the citation against the original before you use it.
APA 7th
Weston, P. S., Simpson, I. J., Ryan, N. S., Ourselin, S., & Fox, N. C. (2015). Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-015-0132-3
Vancouver
Weston PS, Simpson IJ, Ryan NS, Ourselin S, Fox NC. Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration. Alzheimer's research & therapy. 2015. doi:10.1186/s13195-015-0132-3. PMID: 26136857.
BibTeX
@article{weston2015-26136857,
author = {Weston, P. S. and Simpson, I. J. and Ryan, N. S. and Ourselin, S. and Fox, N. C.},
title = {{Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration}},
journal = {Alzheimer's research \& therapy},
year = {2015},
doi = {10.1186/s13195-015-0132-3},
pmid = {26136857},
url = {https://doi.org/10.1186/s13195-015-0132-3}
}
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