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16/100

⚠ Preprint — not yet peer-reviewed alzhub usefulness score 16 out of 100. Disease mechanisms

Topic: Gut, metabolism and diet

Objective Age-related cognitive decline is a major public health concern; however, the biological pathways linking aging to cognitive function remain poorly understood. Emerging evidence suggests that gut microbiota may influence brain health; however, human studies integrating clinical factors, diet, microbiota, and cognition remain limited. Design We conducted a cross-sectional analysis of community-dwelling older adults (N = 578). Clinical variables, blood biomarkers, and dietary intake were assessed using a validated questionnaire, and gut microbiota profiles (based on 16S rRNA sequencing) were analyzed in relation to cognitive function measured using the Mini-Mental State Examination (MMSE). Multivariable regression models were used to identify independent determinants of MMSE. Mediation analysis was performed to evaluate whether the gut microbiota mediated the association between age and cognitive function. Additional analyses were conducted in a subset excluding participants with suspected dementia (MMSE ≤ 23) to examine diet–microbiota relationships (n = 535). Results In multivariable analysis, age, frailty, renal function, inflammatory markers, and specific gut microbial taxa were independently associated with MMSE. Among the microbial features, Bifidobacterium showed a significant positive association with cognitive function. Age was inversely associated with Bifidobacterium , whereas Bifidobacterium was positively associated with MMSE. Mediation analysis demonstrated that Bifidobacterium partially mediated the association between age and MMSE (indirect effect: −0.0107, 95% CI: −0.0196 to − 0.0034, p = 0.004). Furthermore, dietary analysis revealed that milk intake was positively associated with Bifidobacterium , suggesting a modifiable pathway linking diet, microbiota, and cognition. Conclusions Our findings provide evidence that age-related changes in the gut microbiota, particularly reductions in Bifidobacterium , partially mediate cognitive decline in older adults. These results support the existence of a diet–microbiota–brain axis and highlight the gut microbiota as a potential target for interventions aimed at preserving cognitive function during aging. Trial registration number The UMIN Clinical Trials Registry (UMIN-CTR), UMIN000019486, and UMIN0000 000061232 were registered on December 1, 2015, and April 11, 2026, respectively.

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APA 7th

Naito, Y., Yasuda, T., Kitae, H., Mizushima, K., Ouchi, N., Adachi, A., et al. (2026). Gut microbiota mediates the association between aging and cognitive function: evidence from a population-based Kyotango study linking diet, Bifidobacterium, and Mini-Mental State Examination (MMSE) score. Research Square. https://doi.org/10.21203/rs.3.rs-10040802/v1

Vancouver

Naito Y, Yasuda T, Kitae H, Mizushima K, Ouchi N, Adachi A, et al. Gut microbiota mediates the association between aging and cognitive function: evidence from a population-based Kyotango study linking diet, Bifidobacterium, and Mini-Mental State Examination (MMSE) score. Research Square. 2026. doi:10.21203/rs.3.rs-10040802/v1.

BibTeX

@article{naito2026-d413d81c,
  author  = {Naito, Y. and Yasuda, T. and Kitae, H. and Mizushima, K. and Ouchi, N. and Adachi, A. and Kamitani, T. and Narumoto, J. and others},
  title   = {{Gut microbiota mediates the association between aging and cognitive function: evidence from a population-based Kyotango study linking diet, Bifidobacterium, and Mini-Mental State Examination (MMSE) score}},
  journal = {Research Square},
  year    = {2026},
  doi     = {10.21203/rs.3.rs-10040802/v1},
  url     = {https://doi.org/10.21203/rs.3.rs-10040802/v1}
}

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Key findings

Emerging evidence suggests that gut microbiota may influence brain health; however, human studies integrating clinical factors, diet, microbiota, and cognition remain limited.
Results In multivariable analysis, age, frailty, renal function, inflammatory markers, and specific gut microbial taxa were independently associated with MMSE.
Among the microbial features, Bifidobacterium showed a significant positive association with cognitive function.
Age was inversely associated with Bifidobacterium , whereas Bifidobacterium was positively associated with MMSE.
Mediation analysis demonstrated that Bifidobacterium partially mediated the association between age and MMSE (indirect effect: −0.0107, 95% CI: −0.0196 to − 0.0034, p = 0.004).

Study details

Study designcross-sectional
Participants578
Evidence strengthLow

How this study scored 16/100

Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for effect reported and randomised / 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 multi-centre collaboration, so those were left out: it earned 22 of the 62 points we could judge it on, which is 35 out of 100.

Component	Points	Why
Journal tier	2 / 10	Tier 4 — not a peer-reviewed journal (Research Square)
Journal's citation record	0 / 4	Not a journal article, so the journal's record does not count
Study design	4 / 12	A snapshot of people at one point in time
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	2 / 4	578 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	— / 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
Multi-centre 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	22 / 62	Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100.
Total	35 / 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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