Recurrent oral ulcer (ROU) is a prevalent and painful oral disorder with implications beyond physical symptoms, impacting quality of life and necessitating comprehensive management. Understanding the interplays between dietary factors, oral microbiota, and ROU is crucial for developing targeted interventions to improve oral and systemic health. Dietary behaviors and plant-based diet indices including the healthful plant-based diet index (hPDI) were measured based on a validated food frequency questionnaire. Saliva microbial features were profiled using 16S rRNA gene amplicon sequencing. In this cross-sectional study of 579 community-based participants (aged 22–74 years, 66.5% females), 337 participants had ROU. Participants in the highest tertile of hPDI exhibited a 43% lower prevalence of ROU (odds ratio [OR] = 0.57, 95%CI: 0.34–0.94), compared to the lowest tertile, independent of demographics, lifestyle, and major chronic diseases. Participants with ROU tended to have lower oral bacterial richness (Observed ASVs, p < 0.05) and distinct bacterial structure compared to those without ROU (PERMANOVA, p = 0.02). The relative abundances of 16 bacterial genera were associated with ROU (p-FDR < 0.20). Of these, Olsenella, TM7x, and unclassified Muribaculaceae were identified as potential mediators in the association between hPDI and ROU (all p-mediations < 0.05). This study provides evidence of the intricate interplays among dietary factors, oral microbiota, and ROU, offering insights that may inform preventive and therapeutic strategies targeting diets and oral microbiomes.

Mushrooms and algae are important sources of dietary bioactive compounds, but their associations with mortality remain unclear. We examined the association of mushrooms and algae consumption with subsequent risk of all-cause mortality among older adults. This study included 13,156 older adults aged 65 years and above in the Chinese Longitudinal Healthy Longevity Survey (2008–2018). Consumption of mushrooms and algae at baseline and age of 60 were assessed using a simplified food frequency questionnaire (FFQ). We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During 74,976 person-years of follow-up, a total of 8937 death cases were documented. After adjustment for demographic, lifestyle, and other dietary factors, participants who consumed mushrooms and algae at least once per week had a lower risk of all-cause mortality than rare consumers (0–1 time per year) (HR = 0.86; 95% CI: 0.80–0.93). Compared to participants with rare intake at both age 60 and the study baseline (average age of 87), those who maintained regular consumptions over time had the lowest hazard of mortality (HR = 0.86; 95% CI: 0.76–0.98). Our findings supported the potential beneficial role of long-term consumption of mushrooms and algae in reducing all-cause mortality among older adults. Further studies are warranted to evaluate the health benefit for longevity of specific types of mushrooms and algae.

Background/Objectives: Nuts have been associated with various health benefits, yet the evidence regarding their relationship with dementia is inconclusive. This study aims to examine the association between nut consumption and long-term risk of dementia across three prospective cohort studies. Methods: We analyzed data from adults aged 45 and older who were free of dementia at baseline in the Health and Retirement Study (HRS, 2013–2020), the Framingham Offspring Study (FOS, 1998–2018), and the Whitehall II Study (WHII, 2002–2016). Nut consumption, including tree nuts and peanuts, was assessed using validated food frequency questionnaires (FFQs) once at baseline in the HRS and repeatedly across multiple waves in the FOS and WHII. Incident all-cause dementia was identified through a validated algorithm in the HRS, expert panel reviews in the FOS, and healthcare record linkages in the WHII. Cox proportional hazards models were used to estimate the cohort-specific association between nut consumption and incident dementia, which were subsequently pooled. Results: Over 190,914 person-years of follow-up, 992 incident dementia cases occurred among 17,349 participants across the three cohorts. After multivariable adjustments, higher nut consumption was associated with a lower risk of dementia, with pooled hazard ratios (HRs) of 0.80 (95% confidence interval [CI]: 0.69–0.94; I² = 0.0%) for 0.1–5.0 g/day vs. 0 g/day and 0.76 (95% CI: 0.58–0.99; I² = 40.4%) for >5.0 g/day vs. 0 g/day (p-trend = 0.015). Conclusions: Our findings suggest that higher nut consumption was associated with a lower risk of incident dementia among middle-aged and older adults, with evidence of a dose-response trend observed in pooled analyses. These preliminary results support its inclusion as part of an overall brain-healthy dietary pattern.

Background: Tear samples were low‐invasive to access and may reflect changes in the brain. We performed an exploratory proteomic analysis using tear samples to identify proteomic signature and potential pathways that may be associated with mild cognitive impairment (MCI) and dementia.Method: We performed a matched case‐control study using tear samples collected from community‐dwelling older adults, comprising 13 dementia, as well as 34 MCI and 34 age‐, sex‐, educational‐matched normal cognition (NC) controls (age: 73.3 ± 7.1 years; female: 68.4%). The disease staging has been distinguished by clinical dementia rating (CDR). PulseDIA‐based (gas phase fractionation‐assisted data‐independent acquisition mass spectrometry) proteomics analysis was performed. Logistic regression models were used to identify differential proteins when comparing dementia versus NC and conditional logistic regression models were used when comparing MCI versus NC. Identified differential proteins were used to perform enrichment analysis. Lasso regression models were utilized to select protein biomarkers for dementia prediction.Result: A total of 70 tear proteins were found to be significantly associated with dementia and demonstrated same directions in relation to MCI. In particular, 37 proteins were positively related to dementia, with OR ranging from 3.79 (KLHDC4) to 71.91 (GLO1); 33 proteins were inversely related to dementia, with OR ranging from 0.27 (ABCC2) to 0.03 (COPS7B). The 3 strongest pathways identified by the protein‐protein interaction enrichment analysis were central nervous system neuron development, Eukaryotic Translation Termination, and amide biosynthetic process. In addition, incorporating 13 protein biomarkers to the traditional risk factors‐based model significantly improved the predictive ability of dementia (AUC from 0.813 to 0.971, P = 0.032).Conclusion: Differential tear proteins between dementia and normal cognition were identified in this exploratory analysis, which may contribute to discovering novel and low‐invasive biomarkers of dementia.

Background: The irreversible nature of dementia necessitates effective lifestyle modifications for primary prevention. High‐throughput proteomics could offer valuable insights into how healthy lifestyles influence cognitive health and provide clues for targeted interventions. Method: Herein, we conducted comprehensive proteome‐wide association analyses to identify key plasma proteins that mediate the association between an overall healthy lifestyle and the risk of all‐cause dementia. Utilizing data from the UK Biobank, we elucidated the protein mediators of lifestyle‐dementia associations that may serve as intervention intermediate outcomes. Further, we developed and tested a set of lifestyle protein stratification scores (LPSSs) that distinguish targeted populations with high responsiveness of overall and individual lifestyle interventions. Result: We identified twelve plasma proteomic markers associated with both overall healthy lifestyle score and incident dementia (Bonferroni corrected P ‐values <0.05) among 32,029 individuals in the UK Biobank. Aggregately, they mediated 17.6% (95% CI, 10.0%, 29.6%) of the lifestyle‐dementia association. The associations between overall healthy lifestyle score and two key proteomic markers (GDF15 and IGFBP3) were externally replicated in a US‐based cohort. Further, the proteome‐wide interaction analysis revealed that the association between lifestyle and dementia risk varied by specific proteomic features. Using a machine‐learning approach, we developed and tested eight LPSSs to identify participants showing stronger associations between overall or individual healthy lifestyles and dementia. Notably, the LPSS for overall healthy lifestyle, comprising 25 proteins, identified a population with a markedly stronger lifestyle‐dementia association (Hazard Ratio: 0.38, 95%CI: 0.32‐0.45) compared with overall population (0.67, 0.60‐0.75). Individuals with higher LPSS may therefore represent a population who may have stronger responses to healthy lifestyle interventions. Targeting interventions to these specific populations may enhance the effectiveness of dementia prevention. For example, the population attributable fraction of an unhealthy diet increased from 1.63% in the overall population to 29.15% in the targeted group with a higher LPSS for a healthy diet. Conclusion: Our findings indicate that proteomic profiles may serve as intermediate outcomes in lifestyle intervention and facilitate targeted approaches for precision prevention of dementia.