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In Vivo Cortical Microstructure: Relationships With Tauopathy and Cognitive Impairment in the Elderly
Christin Schifani, John A. E. Anderson, Arash Nazeri, Aristotle N. Voineskos, the Alzheimer's Disease Neuroimaging Initiative. Journal of Neurochemistry, 2025-08-01
Topic: Brain proteins, microglia and lab models
ABSTRACT Positron Emission Tomography (PET) of tau is considered “the” indicator of Alzheimer's pathology. However, non‐PET proxies would be helpful for wider accessibility. We used Neurite Orientation Dispersion and Density Imaging (NODDI)‐derived indices (i.e., orientation dispersion [ODI], neurite density [NDI], and free‐water [fISO]) to determine relationships of gray matter microstructure with tau and cognitive impairment. We assessed the fit between NODDI indices, cortical thickness/subcortical volume (CT/ScVol), and tau via multiple factor analysis (MFA) using data from 80 participants from the ADNI‐3 dataset with overlapping multishell diffusion‐weighted and tau‐PET scans ([ 18 F]AV‐1451); 49 were considered cognitively normal older adults (age ~74 years), 26 were diagnosed with mild cognitive impairment (age ~75 years), and five had Alzheimer's dementia (age ~78 years). fISO and tau shared a large amount of spatial overlap, and both strongly correlated with the first MFA dimension. Macrostructural features (i.e., CT/ScVol) were 7% less related to this first MFA dimension than fISO and 8% less than tau. Subsequent mediation analyses demonstrated that fISO mediated the relationship between CT/ScVol and tau, explaining all of the variance. Our results suggest that microstructural features derived from NODDI such as fISO might be useful adjunct markers to tau, which needs to be confirmed in longitudinal studies. Cortical fISO, rather than macrostructure (i.e., CT/ScVol), may represent tau's impact on the brain (and, by extension, cognition). image
Key findings
- Subsequent mediation analyses demonstrated that fISO mediated the relationship between CT/ScVol and tau, explaining all of the variance.
- Our results suggest that microstructural features derived from NODDI such as fISO might be useful adjunct markers to tau, which needs to be confirmed in longitudinal studies.
Why it matters
In 80 participants from the ADNI-3 dataset, a diffusion imaging measure called free-water mediated the relationship between cortical thickness/subcortical volume and tau. The authors suggest this measure might be a useful adjunct marker to tau, but say it needs confirmation in longitudinal studies.
Study details
- Study designlongitudinal study
- Participants80
- Evidence strengthModerate
How this study scored 55/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 53 of the 96 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neurochemistry) |
| Journal's citation record | 3 / 4 | Journal of Neurochemistry: journal h-index 349 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 80 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40751419) |
| Free to read | 2 / 2 | Free to read |
| Points | 53 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 53 of the 96 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1111/jnc.70167
- PubMed: 40751419
- Original source →
- Free full text: Journal of Neurochemistry →
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
Schifani, C., Anderson, J. A. E., Nazeri, A., Voineskos, A. N., & the Alzheimer's Disease Neuroimaging Initiative. (2025). In Vivo Cortical Microstructure: Relationships With Tauopathy and Cognitive Impairment in the Elderly. Journal of Neurochemistry. https://doi.org/10.1111/jnc.70167
Vancouver
Schifani C, Anderson JAE, Nazeri A, Voineskos AN, the Alzheimer's Disease Neuroimaging Initiative. In Vivo Cortical Microstructure: Relationships With Tauopathy and Cognitive Impairment in the Elderly. Journal of Neurochemistry. 2025. doi:10.1111/jnc.70167. PMID: 40751419.
BibTeX
@article{schifani2025-40751419,
author = {Schifani, Christin and Anderson, John A. E. and Nazeri, Arash and Voineskos, Aristotle N. and {the Alzheimer's Disease Neuroimaging Initiative}},
title = {{In Vivo Cortical Microstructure: Relationships With Tauopathy and Cognitive Impairment in the Elderly}},
journal = {Journal of Neurochemistry},
year = {2025},
doi = {10.1111/jnc.70167},
pmid = {40751419},
url = {https://doi.org/10.1111/jnc.70167}
}
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