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Differential associations of insulin resistance with anterior hippocampal volume in mild cognitive impairment and Alzheimer’s disease
Watanabe N, Ogawa A, Osada T, Adachi Y, Shirokoshi T, Kodama H, Oshima Y, Tanaka S et al.. bioRxiv, 2026-08-10
Topic: Brain imaging, connectivity and assessment
Plain-language summary
Insulin resistance is increasingly recognized as a metabolic factor associated with Alzheimer’s disease (AD); however, its relevance to hippocampal structural changes—a key pathological feature of AD—across disease stages is not fully understood. To address this issue, we investigated the relationship between insulin resistance, hippocampal gray matter volume, and cognitive performance using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large-scale neuroimaging dataset. Insulin resistance was assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and its relationship with brain structure and cognitive performance was evaluated across diagnostic groups. In the mild cognitive impairment (MCI) group, higher insulin resistance was associated with larger anterior hippocampal gray matter volume, whereas in the AD group this association was reversed in direction. Furthermore, in the MCI group, anterior hippocampal gray matter volume was also positively associated with higher Mini-Mental State Examination (MMSE) scores, and an exploratory mediation analysis suggested a significant indirect association linking HOMA-IR, anterior hippocampal volume, and cognitive performance through anterior hippocampal volume. These findings suggest that the relationship between insulin resistance and AD-related brain changes differs across diagnostic groups, highlighting the importance of considering metabolic alterations in relation to disease status.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Watanabe, N., Ogawa, A., Osada, T., Adachi, Y., Shirokoshi, T., Kodama, H., et al. (2026). Differential associations of insulin resistance with anterior hippocampal volume in mild cognitive impairment and Alzheimer’s disease. bioRxiv. https://doi.org/10.64898/2026.08.04.742662
Vancouver
Watanabe N, Ogawa A, Osada T, Adachi Y, Shirokoshi T, Kodama H, et al. Differential associations of insulin resistance with anterior hippocampal volume in mild cognitive impairment and Alzheimer’s disease. bioRxiv. 2026. doi:10.64898/2026.08.04.742662.
BibTeX
@article{watanabe2026-72ba0f38,
author = {Watanabe, N. and Ogawa, A. and Osada, T. and Adachi, Y. and Shirokoshi, T. and Kodama, H. and Oshima, Y. and Tanaka, S. and others},
title = {{Differential associations of insulin resistance with anterior hippocampal volume in mild cognitive impairment and Alzheimer’s disease}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.08.04.742662},
url = {https://doi.org/10.64898/2026.08.04.742662}
}
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.
Key findings
- Insulin resistance is increasingly recognized as a metabolic factor associated with Alzheimer’s disease (AD); however, its relevance to hippocampal structural changes—a key pathological feature of AD—across disease stages is not fully understood.
- In the mild cognitive impairment (MCI) group, higher insulin resistance was associated with larger anterior hippocampal gray matter volume, whereas in the AD group this association was reversed in direction.
- Furthermore, in the MCI group, anterior hippocampal gray matter volume was also positively associated with higher Mini-Mental State Examination (MMSE) scores, and an exploratory mediation analysis suggested a significant indirect association linking HOMA-IR, anterior hippocampal volume, and cognitive performance through anterior hippocampal volume.
- These findings suggest that the relationship between insulin resistance and AD-related brain changes differs across diagnostic groups, highlighting the importance of considering metabolic alterations in relation to disease status.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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