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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Nutr.</journal-id>
<journal-title>Frontiers in Nutrition</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Nutr.</abbrev-journal-title>
<issn pub-type="epub">2296-861X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnut.2025.1638315</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Nutrition</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>The association between dietary fiber intake and cognitive function: mediating role of inflammatory markers</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<name><surname>Yan</surname> <given-names>Kaiyun</given-names></name>
<xref ref-type="author-notes" rid="fn001"><sup>&#x02020;</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name><surname>Wang</surname> <given-names>Xinshuo</given-names></name>
<xref ref-type="author-notes" rid="fn001"><sup>&#x02020;</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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</contrib>
<contrib contrib-type="author">
<name><surname>Wang</surname> <given-names>Fengdan</given-names></name>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
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</contrib>
<contrib contrib-type="author">
<name><surname>Chen</surname> <given-names>Baiyang</given-names></name>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Zong</surname> <given-names>Ziyu</given-names></name>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Tian</surname> <given-names>Jing</given-names></name>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Zhao</surname> <given-names>Jing</given-names></name>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Li</surname> <given-names>Bo</given-names></name>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1078847/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
</contrib>
</contrib-group>
<aff><institution>School of Public Health, Jilin University</institution>, <addr-line>Changchun</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Eddy Roccati, University of Tasmania, Australia</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Carlos Miguel Rios-Gonz&#x000E1;lez, Ministerio de Salud P&#x000FA;blica y Bienestar Social, Paraguay</p>
<p>James J. R. Brady, University of Tasmania, Australia</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Bo Li <email>li_bo&#x00040;jlu.edu.cn</email></corresp>
<fn fn-type="equal" id="fn001"><p>&#x02020;These authors have contributed equally to this work and share first authorship</p></fn></author-notes>
<pub-date pub-type="epub">
<day>29</day>
<month>09</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>12</volume>
<elocation-id>1638315</elocation-id>
<history>
<date date-type="received">
<day>30</day>
<month>05</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>02</day>
<month>09</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2025 Yan, Wang, Wang, Chen, Zong, Tian, Zhao and Li.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Yan, Wang, Wang, Chen, Zong, Tian, Zhao and Li</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<abstract>
<sec>
<title>Aims</title>
<p>Cognitive impairment, frequently associated with neurodegenerative diseases such as Alzheimer&#x00027;s disease, may be associated with multiple factors including dietary fiber intake and inflammation. We aimed to explore the associations between reported dietary fiber intake, three novel inflammatory markers, and cognitive function.</p></sec>
<sec>
<title>Methods</title>
<p>This observational and exploratory cross-sectional study utilized the data from the 2011&#x02013;2014 of the National Health and Nutrition Examination Survey (NHANES). Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer&#x00027;s Disease Word Learning (CERAD-WL), CERAD Delayed Recall (CERAD-DR), and Animal Fluency tests (AFT) were used to assess the cognitive function. Linear regression was conducted to explore the relationships between reported dietary fiber intake, three novel inflammatory markers [Albumin-to-alkaline phosphatase ratio (AAPR), Neutrophil-to-Albumin Ratio (NAR), and Systemic Inflammation Response Index (SIRI)] and cognitive function. Mediation analysis was performed to identify the mediating role of inflammatory markers in the relationship between reported dietary fiber intake and cognitive function.</p></sec>
<sec>
<title>Results</title>
<p>The final analysis included 2,461 participants. Reported dietary fiber intake was associated with CERAD-WL (&#x003B2; = 0.042, 95% CI = 0.018 to 0.066), AFT (&#x003B2; = 0.060, 95% CI = 0.020 to 0.100) and inflammatory markers (AAPR: &#x003B2; = 0.003, 95% CI=0.002 to 0.004; NAR: &#x003B2; = &#x02212;0.003, 95% CI = &#x02212;0.006 to &#x02212;0.001; SIRI: &#x003B2; = &#x02212;0.008, 95% CI = &#x02212;0.015 to &#x02212;0.001). AAPR was positively associated with WL (&#x003B2; = 1.184, 95% CI = 0.165 to 2.204) and AFT (&#x003B2; = 1.747, 95% CI = 0.229 to 3.264). AAPR mediated the positive association between reported dietary fiber intake and AFT, with mediation proportion of 17.88%.</p></sec>
<sec>
<title>Conclusions</title>
<p>Reported dietary fiber intake, inflammatory markers, and cognitive function were pairwise associated. The AAPR played a mediating role in the association between reported dietary fiber intake and cognitive function.</p></sec></abstract>
<kwd-group>
<kwd>cognitive function</kwd>
<kwd>dietary fiber intake</kwd>
<kwd>inflammatory markers</kwd>
<kwd>NHANES</kwd>
<kwd>mediation analysis</kwd>
</kwd-group>
<counts>
<fig-count count="3"/>
<table-count count="4"/>
<equation-count count="0"/>
<ref-count count="61"/>
<page-count count="9"/>
<word-count count="7152"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Nutritional Epidemiology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1 Introduction</title>
<p>Cognitive impairment is an age-related state that occurs when various morphological, biochemical, metabolic, and circulatory changes caused by brain aging exceed a certain threshold (<xref ref-type="bibr" rid="B1">1</xref>). Cognitive impairment, the hallmark feature of dementia, is a severe neurological syndrome. Global projections indicate that 152.8 million people were affected by dementia worldwide in 2019 (<xref ref-type="bibr" rid="B2">2</xref>). Mild cognitive impairment (MCI) is often seen as an early indicator of Alzheimer&#x00027;s disease (AD) and is defined as a less severe stage of cognitive impairment, marked by slight alterations in memory and thinking skills (<xref ref-type="bibr" rid="B3">3</xref>). In older adults, dementia and cognitive impairment are the leading causes of long-term functional dependence and decline, leading to decreased quality of life, elevated healthcare expenses, and increased mortality rates (<xref ref-type="bibr" rid="B4">4</xref>). Cognitive impairment adversely influences an individual&#x00027;s capacity for daily living and imposes an economic burden on both society and families (<xref ref-type="bibr" rid="B5">5</xref>). Consequently, it is vital to recognize risk factors for cognitive impairment and inform the public about preventive measures to promote the cognitive health of older adults.</p>
<p>Previous studies have shown that cognitive impairment is associated with various factors such as dietary fiber intake, chronic low-grade inflammatory stress, sleep, and physical condition (<xref ref-type="bibr" rid="B6">6</xref>&#x02013;<xref ref-type="bibr" rid="B9">9</xref>). Research has found higher dietary fiber intake is associated with improved specific components of cognitive function (<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B11">11</xref>). But some studies have also shown that dietary fiber intake is not associated with cognitive impairment in older adults (<xref ref-type="bibr" rid="B12">12</xref>). The effect of dietary fiber intake on cognitive performance in older adults is unclear, more research is needed to demonstrate this.</p>
<p>In addition to dietary factors, chronic inflammation in the body may cause morphological changes in the brain, damaging the normal function of specific areas of the brain, affecting cognitive function (<xref ref-type="bibr" rid="B13">13</xref>). The Albumin to Alkaline Phosphatase Ratio (AAPR), Neutrophil-Albumin Ratio (NAR), and Systemic Inflammatory Response Index (SIRI) are three novel inflammation-related biomarkers that reflect the systemic inflammatory state in the body and have been proven to be effective prognostic indicators for a range of diseases, particularly malignant tumors (<xref ref-type="bibr" rid="B14">14</xref>&#x02013;<xref ref-type="bibr" rid="B16">16</xref>). The SIRI and AAPR were originally designed to predict the prognosis of digestive system cancer, and higher SIRI levels were associated with unfavorable prognostic outcomes (<xref ref-type="bibr" rid="B17">17</xref>, <xref ref-type="bibr" rid="B18">18</xref>). Hooper et al. demonstrated that plasma alkaline phosphatase activity was significantly elevated in patients with AD and inversely correlated with cognitive function (<xref ref-type="bibr" rid="B19">19</xref>). In addition, some studies have confirmed that relatively low serum albumin concentration may be an independent risk factor for MCI in older adults (<xref ref-type="bibr" rid="B20">20</xref>). As a composite biomarker integrating both albumin and alkaline phosphatase, AAPR holds significant promise for assessing neuroinflammation-related cognitive decline. A study detected that NAR and SIRI levels were negatively related to the composite cognitive function score (Z-score) (<xref ref-type="bibr" rid="B21">21</xref>). NAR, as a comprehensive biomarker of neutrophils and albumin, represents the dual effects of neurotoxicity and protection in the acute phase, and can better reflect the degree of immune inflammation than a single indicator (<xref ref-type="bibr" rid="B22">22</xref>). Neutrophil count, lymphocyte count, and monocyte count are all closely related to immunity and inflammation. Given the critical role of inflammation in chronic diseases, hematologic markers readily available from routine blood tests were widely used to assess systemic inflammation (<xref ref-type="bibr" rid="B23">23</xref>). SIRI integrates the above three indicators, which can be used to distinguish the immune inflammatory response of three different pathways <italic>in vivo</italic>, and reflect the immune inflammatory state of the body more comprehensively (<xref ref-type="bibr" rid="B24">24</xref>). However, evidence on the relationships between inflammatory markers and cognitive function across various dimensions remains scarce. Recent evidence suggested that dietary fiber intake could also influence the systemic inflammation (<xref ref-type="bibr" rid="B25">25</xref>). A study by Saeed et al. identified that, in contrast to the high-fiber group, C-reactive protein (CRP) was higher in the low-fiber group (<xref ref-type="bibr" rid="B26">26</xref>). A cross-sectional study demonstrated that there was a significant negative correlation between dietary fiber intake and SIRI (<xref ref-type="bibr" rid="B27">27</xref>).</p>
<p>Recent studies have highlighted the ability of dietary interventions to influence inflammatory pathways associated with cognitive decline (<xref ref-type="bibr" rid="B28">28</xref>). For instance, high-fiber diets were associated with lower concentrations of pro-inflammatory cytokines, which were recognized for their role in neuroinflammation and consequent cognitive decline (<xref ref-type="bibr" rid="B29">29</xref>). Moreover, the Mediterranean diet, rich in dietary fiber, has demonstrated protective effects against cognitive decline, potentially through its anti-inflammatory properties (<xref ref-type="bibr" rid="B30">30</xref>). These findings underscore the importance of considering the impact of diet and inflammation on cognitive health when investigating older adults.</p>
<p>However, few studies have concentrated on the relationships between dietary fiber intake, inflammatory markers and cognitive function. Given the existing evidence regarding the potential advantages of fiber intake in improving inflammation levels and cognitive function, along with the influence of inflammation on cognitive performance, we hypothesized that the positive association between reported dietary fiber intake and cognitive function might be mediated through its anti-inflammatory effects. The objective of this research was to examine associations between reported dietary fiber intake, three inflammatory markers (AAPR, NAR and SIRI) and cognitive function and to determine the mediating role of inflammatory markers in the association of reported dietary fiber intake and cognitive function.</p></sec>
<sec id="s2">
<title>2 Materials and methods</title>
<sec>
<title>2.1 Study population</title>
<p>This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES), a national survey employing a complex, multistage, and probabilistic sampling design to evaluate the health status of U.S. adults. This program consists of five main data sets collected through interviews and physical examinations, including demographic information, diet, medical assessment, laboratory results and questionnaire data. Each participant completed the questionnaire and underwent examinations at the mobile examination center (MEC) over the course of 1 year, in order to obtain important research variables. The study included 3,632 adults aged 60 and above in NHANES from 2011 to 2014. Additionally, considering the complex sampling design and sample weights of NHANES, we removed missing values. 564 participants were excluded due to incomplete or unreliable 24-h recall data. Individuals who had extreme total energy intakes of &#x0003C; 500 or &#x0003E; 5,000 kcal/day for women (<italic>n</italic> = 13), and &#x0003C; 500 or &#x0003E; 8,000 kcal/day for men (<italic>n</italic> = 5) (<xref ref-type="bibr" rid="B31">31</xref>, <xref ref-type="bibr" rid="B32">32</xref>) were further omitted. Participants with missing data on cognitive measures (<italic>n</italic> = 350), AAPR, NAR and SIRI (<italic>n</italic> = 149), and other covariates (<italic>n</italic> = 90) were excluded. Ultimately, a total of 2,461 participants were incorporated into this study, as detailed in <xref ref-type="fig" rid="F1">Figure 1</xref>.</p>
<fig position="float" id="F1">
<label>Figure 1</label>
<caption><p>Flow chart portraying participant inclusion and exclusion in the current study.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-12-1638315-g0001.tif">
<alt-text>Flowchart illustrating sample size reduction in a study. Initial sample is 3,632 participants from NHANES 2011&#x02013;2012 and 2013&#x02013;2014. 582 are excluded due to abnormal energy intake and missing dietary data, leaving 3,050. Further exclusions due to missing cognitive, AAPR, NAR, SIRI, BMI, smoking, drinking, education, and diabetes data reduce the sample to 2,461.</alt-text>
</graphic>
</fig>
<p>The NCHS ethics review board approved the NHANES study protocols, and all participants signed informed consent forms.</p></sec>
<sec>
<title>2.2 Reported dietary fiber intake</title>
<p>Participants underwent two interviews recalling dietary intake across the past 24-h, the initial one took place face-to-face at a mobile test center, while 3 to 10 days later, the second occurred over the phone. If dietary recall data for 2 days were available, the average was calculated. Otherwise, a single dietary recall was used (<xref ref-type="bibr" rid="B33">33</xref>).</p></sec>
<sec>
<title>2.3 Cognitive function</title>
<p>This study assessed cognitive performance by four cognitive tests: Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer&#x00027;s Disease Word Learning (CERAD-WL), CERAD Delayed Recall (CERAD-DR) and Animal Fluency tests (AFT) (<xref ref-type="bibr" rid="B34">34</xref>). The DSST was a paper-and-pencil cognitive test presented on a sheet of paper, which could be used to assess the reaction speed, long-term attention, and working memory of the subjects (<xref ref-type="bibr" rid="B35">35</xref>). The CERAD-WL requires participants to recall as many words as possible after reading 10 unrelated words aloud in various orders, for a total of 30 points. The CERAD-DR was performed after the AFT and DSST. Participants were asked to recall words from the CERAD-WL test, which was used to assess transient and delayed learning abilities. AFT was used to assess verbal fluency, in which participants were required to name as many animals as possible within 1 min, without any prompts. A Z-score was employed as a standardized measure of total cognitive performance to eliminate discrepancies in individual cognitive scores in this investigation. The Z-score was calculated as Z = (x-m)/&#x003C3;, where x was the raw score, m was the population mean, and &#x003C3; was the population SD. Composite Z-scores were created by summing the Z-scores of these four individual tests (DSST, AFT, CERAD-WL, CERAD-DR) (<xref ref-type="bibr" rid="B36">36</xref>). Z scores &#x0003C; -1 were characterized as &#x0201C;cognitive impairment&#x0201D; (<xref ref-type="bibr" rid="B37">37</xref>).</p></sec>
<sec>
<title>2.4 Definition of inflammatory markers (AAPR, NAR and SIRI)</title>
<p>Peripheral blood samples from NHANES participants were analyzed at a mobile Examination center (MEC) using a Beckman Coulter HMX hematology analyzer. Lymphocyte, neutrophil, and monocyte counts were measured by complete blood count. The Beckman UniCel<sup>&#x000AE;</sup>DxC800 Synchron analyzer was employed to assess serum ALP levels and serum albumin levels. Based on peripheral blood cell counts, AAPR, NAR, and SIRI are calculated as follows. AAPR = albumin (g/L)/alkaline phosphatase (U/L) (<xref ref-type="bibr" rid="B38">38</xref>), NAR = neutrophil count (10<sup>9</sup>/L)/albumin (g/dL) (<xref ref-type="bibr" rid="B39">39</xref>), SIRI = monocyte count (10<sup>9</sup>/L) &#x000D7; neutrophils count (10<sup>9</sup>/L)/lymphocyte count (10<sup>9</sup>/L) (<xref ref-type="bibr" rid="B40">40</xref>). The specific measures and detailed information can be found in the NHANES Laboratory/Medical Technician Procedures Manual (<xref ref-type="bibr" rid="B41">41</xref>).</p></sec>
<sec>
<title>2.5 Covariates</title>
<p>We adjusted covariates factors that might be associated with reported dietary fiber intake and cognitive function (including age, sex, race, education status, body mass index (BMI), smoking status, drinking status, energy intake (<xref ref-type="bibr" rid="B42">42</xref>) and history of diabetes). Smoking status was assessed as non-smokers (had smoked &#x0003C; 100 cigarettes in their entire life), former smoker (had smoked &#x02265; 100 cigarettes in their entire life and answered negatively to the question, &#x0201C;Do you smoke now?&#x0201D;), or current smoker (&#x02265; 100 cigarettes in their entire life and answered affirmatively to the question, &#x0201C;Do you smoke now?&#x0201D;). Smoking status was categorized into &#x0201C;never smokers&#x0201D; and &#x0201C;ever smokers&#x0201D; by combining former smokers and current smokers (<xref ref-type="bibr" rid="B43">43</xref>). Drinking status was classified into never drinkers (no alcohol consumption throughout lifetime or in the past 12 months), former drinkers (prior alcohol consumption but no intake in the past 12 months), and current drinkers (consumption of &#x02265;12 alcoholic drinks in the past year or in their lifetimes and at least one drinking day reported in the past year). The drinking status was later categorized as &#x0201C;never drinker&#x0201D; and &#x0201C;ever drinker&#x0201D; by combing former and current drinkers (<xref ref-type="bibr" rid="B44">44</xref>). BMI was categorized into three categories: underweight or healthy weight (BMI &#x0003C; 25.0 kg/m<sup>2</sup>), overweight (25.0 &#x02264; BMI &#x0003C; 30.0 kg/m<sup>2</sup>), and obese (&#x02265; 30.0 kg/m<sup>2</sup>). Energy intake was categorized into three categories: low intake (500 to 1,600 per day for women, 500 to 2,000 calories per day for men), adequate intake (1,600 to 2,400 calories per day for women, 2,000 to 3,000 calories per day for men) and high intake (&#x0003E;2,400 calories per day for women and 3,000 calories per day for men) (<xref ref-type="bibr" rid="B45">45</xref>).</p></sec>
<sec>
<title>2.6 Statistical analysis</title>
<p>According to the analysis guidelines of NHANES, weighting was performed using strata, PSU and weight. The weight used was WTDRD1 or WTDR2D. All the statistical analysis was conducted under the instruction of NHANES complex sample weight. In this study, IBM SPSS24.0 software and R4.3.2 were used to analyze the data. Continuous and categorical data were characterized using medians (IQRs) or numbers (weighted proportions), respectively. Differences between groups in continuous and categorical variables were assessed by the Wilcoxon rank-sum test and chi-square test, respectively. Linear regression was conducted to explore the relationships between reported dietary fiber intake, inflammatory markers and cognitive function. The results were presented as regression coefficients (&#x003B2;) and 95% confidence intervals (CI). Model 1 was adjusted for sex, age, race, and education status, and model 2 further adjusted for BMI, smoking status, drinking status, energy intake and history of diabetes based on model 1. The multicollinearity of the independent variables was tested by calculating the variance inflation factor (VIF). The VIF values of all independent variables were &#x0003C; 5, indicating that there was no significant multicollinearity problem in the model. Finally, mediation analysis was performed by &#x0201C;mediation&#x0201D; packages to explore the mediating role of inflammatory markers in the relationship between reported dietary fiber intake and cognitive function. The bootstrap method was used to obtain the CI of the indirect effect. The proportion of the mediated effect was calculated using the following formula: (mediated effect/total effect) &#x000D7; 100%. Statistical significance was determined when the two-tailed <italic>P</italic>-value &#x0003C; 0.05. No multiple comparison correction was performed.</p></sec></sec>
<sec id="s3">
<title>3 Results</title>
<sec>
<title>3.1 General characteristics</title>
<p>Among the 2,461 participants involved in this study, 422 (9.9%) were assigned to the cognitively impaired group. As shown in <xref ref-type="table" rid="T1">Table 1</xref>, reported fiber intake and AAPR in cognitive impairment group were lower than that in non-cognitive impairment group, while NAR was higher in cognitive impairment group. SIRI had no differences between participants with and without cognitive impairment. Meanwhile, there were differences in age, race, education status, drinking status, history of diabetes and energy intake (<italic>P</italic> &#x0003C; 0.05).</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Characteristics of participants [median (IQR)/n (%)].</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Characteristics</bold></th>
<th valign="top" align="center"><bold>Total <italic>n</italic> = 2,461</bold></th>
<th valign="top" align="center"><bold>Non-cognitive impairment <italic>n</italic> = 2,039 (90.1%)</bold></th>
<th valign="top" align="center"><bold>Cognitive impairment <italic>n</italic> = 422(9.9%)</bold></th>
<th valign="top" align="center"><bold><italic>Z/&#x003C7;<sup>2</sup></italic></bold></th>
<th valign="top" align="center"><bold><italic>P</italic>-value</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Fiber intake, g/d</td>
<td valign="top" align="center">16.05 (11.70,21.80)</td>
<td valign="top" align="center">16.30 (12.00,22.20)</td>
<td valign="top" align="center">13.50 (9.65,18.15)</td>
<td valign="top" align="center">6.330</td>
<td valign="top" align="center">&#x0003C; 0.001</td>
</tr> <tr>
<td valign="top" align="left">AAPR</td>
<td valign="top" align="center">0.66 (0.54,0.81)</td>
<td valign="top" align="center">0.67 (0.55,0.82)</td>
<td valign="top" align="center">0.57 (0.45,0.73)</td>
<td valign="top" align="center">&#x02212;5.792</td>
<td valign="top" align="center">&#x0003C; 0.001</td>
</tr> <tr>
<td valign="top" align="left">NAR</td>
<td valign="top" align="center">0.93 (0.74,1.21)</td>
<td valign="top" align="center">0.93 (0.74,1.19)</td>
<td valign="top" align="center">1.02 (0.78,1.37)</td>
<td valign="top" align="center">&#x02212;2.723</td>
<td valign="top" align="center">0.006</td>
</tr> <tr>
<td valign="top" align="left">SIRI</td>
<td valign="top" align="center">1.17 (0.81,1.84)</td>
<td valign="top" align="center">1.17 (0.81,1.81)</td>
<td valign="top" align="center">1.26 (0.83,2.04)</td>
<td valign="top" align="center">&#x02212;1.311</td>
<td valign="top" align="center">0.190</td>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>Age, years</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">96.054</td>
<td valign="top" align="center">&#x0003C; 0.001</td>
</tr> <tr>
<td valign="top" align="left">60&#x02013;70</td>
<td valign="top" align="center">1,463 (62.0)</td>
<td valign="top" align="center">1,289 (65.2)</td>
<td valign="top" align="center">174 (33.1)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">&#x0003E;70</td>
<td valign="top" align="center">998 (38.0)</td>
<td valign="top" align="center">720 (34.8)</td>
<td valign="top" align="center">248 (66.9)</td>
<td/>
<td/>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>Sex</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">0.136</td>
<td valign="top" align="center">0.759</td>
</tr> <tr>
<td valign="top" align="left">Male</td>
<td valign="top" align="center">1,223 (47.7)</td>
<td valign="top" align="center">983 (47.8)</td>
<td valign="top" align="center">240 (46.6)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Female</td>
<td valign="top" align="center">1,238 (52.3)</td>
<td valign="top" align="center">1,056 (52.2)</td>
<td valign="top" align="center">182 (53.4)</td>
<td/>
<td/>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>Race</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">126.956</td>
<td valign="top" align="center">&#x0003C; 0.001</td>
</tr> <tr>
<td valign="top" align="left">Non-Hispanic White</td>
<td valign="top" align="center">1,245 (79.1)</td>
<td valign="top" align="center">1,114 (82.1)</td>
<td valign="top" align="center">131 (51.2)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Other</td>
<td valign="top" align="center">1,216 (20.9)</td>
<td valign="top" align="center">925 (17.9)</td>
<td valign="top" align="center">291 (48.8)</td>
<td/>
<td/>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>Education status</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">219.465</td>
<td valign="top" align="center">&#x0003C; 0.001</td>
</tr> <tr>
<td valign="top" align="left">Below high school</td>
<td valign="top" align="center">586 (14.8)</td>
<td valign="top" align="center">342 (11.5)</td>
<td valign="top" align="center">244 (45.4)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">High school</td>
<td valign="top" align="center">581 (22.4)</td>
<td valign="top" align="center">491 (22.0)</td>
<td valign="top" align="center">90 (25.4)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Above high school</td>
<td valign="top" align="center">1,294 (62.8)</td>
<td valign="top" align="center">1,206 (66.5)</td>
<td valign="top" align="center">88 (29.2)</td>
<td/>
<td/>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>BMI</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">7.075</td>
<td valign="top" align="center">0.206</td>
</tr> <tr>
<td valign="top" align="left">Under and healthy weight</td>
<td valign="top" align="center">648 (26.7)</td>
<td valign="top" align="center">527 (26.0)</td>
<td valign="top" align="center">121 (33.7)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Overweight</td>
<td valign="top" align="center">873 (35.8)</td>
<td valign="top" align="center">726 (36.3)</td>
<td valign="top" align="center">147 (30.7)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Obese</td>
<td valign="top" align="center">940 (37.5)</td>
<td valign="top" align="center">786 (37.7)</td>
<td valign="top" align="center">154 (35.6)</td>
<td/>
<td/>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>Smoking status</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">0.196</td>
<td valign="top" align="center">0.627</td>
</tr> <tr>
<td valign="top" align="left">Never smoker</td>
<td valign="top" align="center">1,215 (51.1)</td>
<td valign="top" align="center">1,014 (51.2)</td>
<td valign="top" align="center">201 (49.7)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Ever smoker</td>
<td valign="top" align="center">1,246 (48.9)</td>
<td valign="top" align="center">1,025 (48.8)</td>
<td valign="top" align="center">221 (50.3)</td>
<td/>
<td/>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>Drinking status</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">11.195</td>
<td valign="top" align="center">0.006</td>
</tr> <tr>
<td valign="top" align="left">Never drinker</td>
<td valign="top" align="center">360 (12.4)</td>
<td valign="top" align="center">282 (11.7)</td>
<td valign="top" align="center">78 (19.1)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Ever drinker</td>
<td valign="top" align="center">2,101 (87.6)</td>
<td valign="top" align="center">1,757 (88.3)</td>
<td valign="top" align="center">344 (80.9)</td>
<td/>
<td/>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>Diabetes</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">26.182</td>
<td valign="top" align="center">&#x0003C; 0.001</td>
</tr> <tr>
<td valign="top" align="left">No</td>
<td valign="top" align="center">1,787 (78.0)</td>
<td valign="top" align="center">1,528 (79.4)</td>
<td valign="top" align="center">259 (65.1)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Yes</td>
<td valign="top" align="center">674 (22.0)</td>
<td valign="top" align="center">511 (20.6)</td>
<td valign="top" align="center">163 (34.9)</td>
<td/>
<td/>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left"><bold>Energy intake</bold></td>
<td/>
<td/>
<td/>
<td valign="top" align="center">&#x02212;8.854</td>
<td valign="top" align="center">&#x0003C; 0.001</td>
</tr> <tr>
<td valign="top" align="left">Low</td>
<td valign="top" align="center">1,282 (44.6)</td>
<td valign="top" align="center">981 (41.9)</td>
<td valign="top" align="center">301 (68.8)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">Adequate</td>
<td valign="top" align="center">979 (46.4)</td>
<td valign="top" align="center">870 (48.5)</td>
<td valign="top" align="center">109 (27.3)</td>
<td/>
<td/>
</tr> <tr>
<td valign="top" align="left">High</td>
<td valign="top" align="center">200 (9.0)</td>
<td valign="top" align="center">188 (9.6)</td>
<td valign="top" align="center">12 (3.9)</td>
<td/>
<td/>
</tr></tbody>
</table>
<table-wrap-foot>
<p>AAPR, albumin to alkaline phosphatase ratio; NAR, neutrophil-to-albumin ratio; SIRI, systemic inflammation response index; BMI, Body Mass Index.</p>
</table-wrap-foot>
</table-wrap></sec>
<sec>
<title>3.2 Correlations of reported dietary fiber intake with cognitive function and inflammatory markers</title>
<p>As shown in <xref ref-type="table" rid="T2">Table 2</xref>, higher reported dietary fiber intake was associated with higher cognitive function scores of CERAD-WL, DSST and AFT in the crude model. Reported dietary fiber intake remained a significant association with CERAD-WL (&#x003B2; = 0.042, 95% CI = 0.018 to 0.066) and AFT (&#x003B2; = 0.060, 95% CI = 0.020 to 0.100) in the fully adjusted model, which implied that increasing reported dietary fiber intake by 1 g/day increased CERAD-WL and AFT scores by 0.042 and 0.060 points, respectively.</p>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>Linear regression model for reported dietary fiber intake on cognitive performance.</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Cognitive performance</bold></th>
<th valign="top" align="center"><bold>&#x003B2; (95%CI)</bold></th>
<th valign="top" align="center"><bold><italic>P</italic>-value</bold></th>
</tr>
</thead>
<tbody>
<tr style="background-color:#dee1e1;">
<td valign="top" align="left" colspan="3"><bold>CERAD-WL</bold></td>
</tr> <tr>
<td valign="top" align="left">Crude model</td>
<td valign="top" align="center">0.053 (0.029, 0.076)</td>
<td valign="top" align="center"><bold>&#x0003C; 0.001</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 1</td>
<td valign="top" align="center">0.051 (0.032, 0.071)</td>
<td valign="top" align="center"><bold>&#x0003C; 0.001</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 2</td>
<td valign="top" align="center">0.042 (0.018, 0.066)</td>
<td valign="top" align="center"><bold>0.001</bold></td>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left" colspan="3"><bold>CERAD-DR</bold></td>
</tr> <tr>
<td valign="top" align="left">Crude model</td>
<td valign="top" align="center">0.015 (0.000, 0.030)</td>
<td valign="top" align="center">0.055</td>
</tr> <tr>
<td valign="top" align="left">Model 1</td>
<td valign="top" align="center">0.014 (&#x02212;0.001, 0.028)</td>
<td valign="top" align="center">0.061</td>
</tr> <tr>
<td valign="top" align="left">Model 2</td>
<td valign="top" align="center">0.010 (&#x02212;0.004, 0.025)</td>
<td valign="top" align="center">0.157</td>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left" colspan="3"><bold>DSST</bold></td>
</tr> <tr>
<td valign="top" align="left">Crude model</td>
<td valign="top" align="center">0.195 (0.086, 0.304)</td>
<td valign="top" align="center"><bold>0.001</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 1</td>
<td valign="top" align="center">0.125 (0.029, 0.220)</td>
<td valign="top" align="center"><bold>0.012</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 2</td>
<td valign="top" align="center">0.103 (&#x02212;0.005, 0.210)</td>
<td valign="top" align="center">0.061</td>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left" colspan="3"><bold>AFT</bold></td>
</tr> <tr>
<td valign="top" align="left">Crude model</td>
<td valign="top" align="center">0.097 (0.057, 0.138)</td>
<td valign="top" align="center"><bold>&#x0003C; 0.001</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 1</td>
<td valign="top" align="center">0.072 (0.033, 0.111)</td>
<td valign="top" align="center"><bold>0.001</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 2</td>
<td valign="top" align="center">0.060 (0.020, 0.100)</td>
<td valign="top" align="center"><bold>0.005</bold></td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>Crude model: no covariates adjusted.</p>
<p>Model 1 = Sex &#x0002B; Age &#x0002B; Race &#x0002B; Education status.</p>
<p>Model 2 = Model 1 &#x0002B; BMI &#x0002B; Smoking status &#x0002B; Drinking status &#x0002B; Diabetes&#x0002B; Energy intake.</p>
<p>CERAD-WL, Consortium to Establish a Registry for Alzheimer&#x00027;s Disease Word Learning; CERAD-DR, CERAD Delayed Recall; DSST, Digit Symbol Substitution Test; AFT, Animal Fluency tests; BMI, Body Mass Index. The bold values represent statistically significant results.</p>
</table-wrap-foot>
</table-wrap>
<p>Reported dietary fiber intake was associated with AAPR and NAR in the crude model. Similarly, reported dietary fiber intake was significantly associated with AAPR (&#x003B2; = 0.003, 95% CI = 0.002 to 0.004), NAR (&#x003B2; = &#x02212;0.003, 95% CI = &#x02212;0.006 to &#x02212;0.001), and SIRI (&#x003B2; = &#x02212;0.008, 95% CI = &#x02212;0.015 to &#x02212;0.001) in the fully adjusted model (<xref ref-type="table" rid="T3">Table 3</xref>), which implied that increasing reported dietary fiber intake by 1 g/day increased AAPR by 0.003 and decreased NAR and SIRI by 0.003 and 0.008, respectively.</p>
<table-wrap position="float" id="T3">
<label>Table 3</label>
<caption><p>Linear regression model for reported dietary fiber intake on inflammatory markers.</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Inflammatory markers</bold></th>
<th valign="top" align="center"><bold>&#x003B2; (95%CI)</bold></th>
<th valign="top" align="center"><bold><italic>P</italic>-value</bold></th>
</tr>
</thead>
<tbody>
<tr style="background-color:#dee1e1;">
<td valign="top" align="left" colspan="3"><bold>AAPR</bold></td>
</tr> <tr>
<td valign="top" align="left">Crude model</td>
<td valign="top" align="center">0.002 (0.001, 0.004)</td>
<td valign="top" align="center"><bold>0.001</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 1</td>
<td valign="top" align="center">0.002 (0.000, 0.003)</td>
<td valign="top" align="center"><bold>0.019</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 2</td>
<td valign="top" align="center">0.003 (0.002, 0.004)</td>
<td valign="top" align="center"><bold>&#x0003C; 0.001</bold></td>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left" colspan="3"><bold>NAR</bold></td>
</tr> <tr>
<td valign="top" align="left">Crude model</td>
<td valign="top" align="center">&#x02212;0.004 (&#x02212;0.006, &#x02212;0.002)</td>
<td valign="top" align="center"><bold>&#x0003C; 0.001</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 1</td>
<td valign="top" align="center">&#x02212;0.004 (&#x02212;0.006, &#x02212;0.002)</td>
<td valign="top" align="center"><bold>&#x0003C; 0.001</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 2</td>
<td valign="top" align="center">&#x02212;0.003 (&#x02212;0.006, &#x02212;0.001)</td>
<td valign="top" align="center"><bold>0.013</bold></td>
</tr> <tr style="background-color:#dee1e1;">
<td valign="top" align="left" colspan="3"><bold>SIRI</bold></td>
</tr> <tr>
<td valign="top" align="left">Crude model</td>
<td valign="top" align="center">&#x02212;0.004 (&#x02212;0.009, 0.002)</td>
<td valign="top" align="center">0.224</td>
</tr> <tr>
<td valign="top" align="left">Model 1</td>
<td valign="top" align="center">&#x02212;0.007 (&#x02212;0.013, &#x02212;0.001)</td>
<td valign="top" align="center"><bold>0.025</bold></td>
</tr> <tr>
<td valign="top" align="left">Model 2</td>
<td valign="top" align="center">&#x02212;0.008 (&#x02212;0.015, &#x02212;0.001)</td>
<td valign="top" align="center"><bold>0.018</bold></td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>Crude model: no covariates adjusted.</p>
<p>Model 1 = Sex &#x0002B; Age &#x0002B; Race &#x0002B; Education status.</p>
<p>Model 2 = Model 1 &#x0002B; BMI &#x0002B; Smoking status &#x0002B; Drinking status &#x0002B; Diabetes&#x0002B; Energy intake.</p>
<p>AAPR, albumin to alkaline phosphatase ratio; NAR, neutrophil-to-albumin ratio; SIRI, systemic inflammation response index; BMI, Body Mass Index. The bold values represent statistically significant results.</p>
</table-wrap-foot>
</table-wrap></sec>
<sec>
<title>3.3 Associations between inflammatory markers and cognitive function</title>
<p>As shown in <xref ref-type="fig" rid="F2">Figure 2</xref>, in model 2, AAPR was significantly positively associated with CERAD-WL (&#x003B2; = 1.184, 95% CI = 0.165 to 2.204) and AFT (&#x003B2; = 1.747, 95% CI = 0.229 to 3.264). NAR was significantly negatively associated with DSST (&#x003B2; = &#x02212;2.930, 95% CI = &#x02212;5.257 to &#x02212;0.604), and SIRI was negatively associated with CERAD-DR (&#x003B2; = &#x02212;0.183, 95% CI = &#x02212;0.292 to &#x02212;0.075).</p>
<fig position="float" id="F2">
<label>Figure 2</label>
<caption><p>Forest plot of the association between inflammatory markers and cognitive function. Linear regression model illustrating the association between reported dietary fiber intake (g) and cognitive function across multiple cognitive assessments. The black solid line represents 0, the blue solid line represents the 95% confidence interval, and the blue square represents the estimated value (&#x003B2;). Adjusted for sex, age, race, education status, smoking status, drinking status, BMI, diabetes, energy intake. CERAD-WL, Consortium to Establish a Registry for Alzheimer&#x00027;s Disease Word Learning; CERAD-DR, CERAD Delayed Recall; DSST, Digit Symbol Substitution Test; AFT, Animal Fluency tests; AAPR, albumin to alkaline phosphatase ratio.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-12-1638315-g0002.tif">
<alt-text>Forest plot showing the relationship between inflammatory markers (AAPR, NAR, SIRI) and cognitive performance (CERAD-WL, CERAD-DR, DSST, AFT). Each row displays coefficient with a 95% confidence interval (CI) and a P-value, indicating the strength and significance of associations. Positive values suggest an association with improved cognitive performance, while negative values indicate a decline. Key significant findings include AAPR with DSST (= 3.688, P = 0.0105) and AFT (1.747, P = 0.025), suggesting a positive association.</alt-text>
</graphic>
</fig></sec>
<sec>
<title>3.4 Mediating effect of inflammatory markers on reported dietary fiber intake and cognitive function</title>
<p>As shown in <xref ref-type="table" rid="T4">Table 4</xref>, the effects of reported dietary fiber intake on WL and AFT were reduced after adjusting for inflammatory markers. AAPR mediated the association between reported dietary fiber intake and AFT (proportion of medaiiton: 17.88%; indirect effect = 0.0123; 95% CI = 0.0002 to 0.0100; <xref ref-type="fig" rid="F3">Figure 3</xref>). However, no mediating effect of AAPR was observed in the association between reported dietary fiber intake and CERAD-WL (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure 1</xref>).</p>
<table-wrap position="float" id="T4">
<label>Table 4</label>
<caption><p>Linear regression model for reported dietary fiber intake and AAPR on CERAD-WL and AFT.</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Cognitive performance</bold></th>
<th valign="top" align="center"><bold>Variables</bold></th>
<th valign="top" align="center"><bold>&#x003B2; (95%CI)</bold></th>
<th valign="top" align="center"><bold><italic>P</italic></bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">CERAD-WL</td>
<td valign="top" align="center">Reported dietary fiber intake</td>
<td valign="top" align="center"><bold>0.039 (0.014, 0.064)</bold></td>
<td valign="top" align="center"><bold>0.003</bold></td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">AAPR</td>
<td valign="top" align="center"><bold>1.057 (0.035, 2.080)</bold></td>
<td valign="top" align="center"><bold>0.043</bold></td>
</tr> <tr>
<td valign="top" align="left">AFT</td>
<td valign="top" align="center">Reported dietary fiber intake</td>
<td valign="top" align="center"><bold>0.055 (0.015, 0.095)</bold></td>
<td valign="top" align="center"><bold>0.008</bold></td>
</tr>
 <tr>
<td/>
<td valign="top" align="center">AAPR</td>
<td valign="top" align="center"><bold>1.567 (0.057, 3.077)</bold></td>
<td valign="top" align="center"><bold>0.042</bold></td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>Adjusted for sex, age, race, education status, smoking status, drinking status, BMI, diabetes and energy intake.</p>
<p>CERAD-WL, Consortium to Establish a Registry for Alzheimer&#x00027;s Disease Word Learning; AFT, Animal Fluency tests; BMI, Body Mass Index; AAPR, albumin to alkaline phosphatase ratio.</p>
<p>The &#x0201C;AAPR&#x0201D; row represents adding the &#x0201C;AAPR&#x0201D; variable to the model. The bold values represent statistically significant results.</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="F3">
<label>Figure 3</label>
<caption><p>Mediation models. Figure demonstrating mediation models with independent variables of reported dietary fiber intake, mediators of AAPR and dependent variable of AFT. IE, Indirect effect; DE, Direct effect. Adjusted for sex, age, race, education status, smoking status, drinking status, BMI, diabetes and energy intake. AFT, Animal Fluency tests; AAPR, albumin to alkaline phosphatase ratio.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-12-1638315-g0003.tif">
<alt-text>Mediation analysis diagram illustrating the relationship between reported dietary fiber intake, AAPR, and AFT. Indirect effect (IE) is 0.0123 with a 95% confidence interval (CI) of 0.0002 to 0.0100, P = 0.032. Proportion of mediation is 17.88% with P = 0.036. Direct effect (DE) is 0.0566 with a 95% CI of 0.0165 to 0.0900, P = 0.004.</alt-text>
</graphic>
</fig>
</sec></sec>
<sec id="s4">
<title>4 Discussion</title>
<p>This study demonstrated the association between higher reported dietary fiber intake and better cognitive performance assessed by CERAD-WL and AFT, and the association between higher AAPR and better cognitive performance measured by CERAD-WL and AFT also. In addition, AAPR played a mediating role in the relationship between reported dietary fiber intake and cognitive function, with a mediation proportion of 17.88%.</p>
<p>He et al. analyzed 2,713 older adults and found that dietary fiber had a significant positive correlation with AFT in the fourth quarter (<xref ref-type="bibr" rid="B42">42</xref>). Previous studies have demonstrated that fiber intake was positively associated with AFT and WL (<xref ref-type="bibr" rid="B46">46</xref>). These findings are consistent with our results, demonstrating that higher fiber intake is associated with better performance on both CERAD-WL and AFT. However, the relationship between fiber intake and DSST remains controversial. A study demonstrated a significant association between dietary fiber and the DSST in older adults, revealing an approximate linear dose-response relationship between dietary fiber intake and DSST (<xref ref-type="bibr" rid="B10">10</xref>). However, some previous studies found no association between dietary fiber intake and DSST (<xref ref-type="bibr" rid="B11">11</xref>), which was similar to our finding. More persuasive studies are needed to further explore the relationship of fiber with DSST. Future studies should employ longitudinal designs to clarify the temporal relationship between dietary fiber intake and specific cognitive domains, particularly DSST. The potential mechanisms underlying the observed association between dietary fiber consumption and lower cognitive decline have not been fully elucidated. The gut microbiome significantly affects brain function via the gut-brain axis (<xref ref-type="bibr" rid="B47">47</xref>). After reaching the colon, dietary fiber is fermented and metabolized by bacteria to produce short-chain fatty acids (SCFA) (<xref ref-type="bibr" rid="B48">48</xref>), exerting their metabolic benefits through gut-cranial neural circuits (<xref ref-type="bibr" rid="B49">49</xref>). SCFAs such as acetate, propionate, and butyrate regulate neuroinflammation and synaptic growth, survival, and differentiation (<xref ref-type="bibr" rid="B50">50</xref>). These interactions underscore the significant function of dietary fiber not just in digestive health but also in sustaining cognitive vitality through complex biological pathways.</p>
<p>Our findings suggested that dietary fiber may beneficially influence inflammatory level, while higher inflammation levels showed a strong association with poorer cognitive function. Dietary fiber plays an anti-inflammatory role by changing intestinal flora and producing short-chain fatty acids (<xref ref-type="bibr" rid="B51">51</xref>). Another study showed that dietary fiber could directly attenuate the production of inflammatory cytokines by dendritic cells co-cultured with intestinal epithelial supernatants through interaction with Toll-like receptors (<xref ref-type="bibr" rid="B52">52</xref>). Chronic inflammation is a key pathogenetic element that leads to the progression of AD and cognitive impairment. Chronic inflammation in the body may cause morphological changes in the brain and impair the normal function of specific brain regions (<xref ref-type="bibr" rid="B13">13</xref>). In addition, inflammation also disrupts the integrity of the blood-brain barrier (<xref ref-type="bibr" rid="B53">53</xref>), allowing inflammatory markers to penetrate and irritate nerves, resulting in neurodegeneration. Our findings revealed that AAPR partly mediated the association between fiber intake and cognitive function among older adults, accounting for 17.88% of the total effect. AAPR can be utilized to forecast the prognosis of cancer, such as lung cancer (<xref ref-type="bibr" rid="B54">54</xref>) and cholangiocarcinoma (<xref ref-type="bibr" rid="B55">55</xref>). Higher AAPR reflects elevated albumin and reduced ALP, potentially benefiting cognition through dual pathways: albumin maintains blood volume, regulates osmotic pressure, transports nutrients and metabolites, and acts as an antioxidant, all of which are beneficial to brain cells (<xref ref-type="bibr" rid="B56">56</xref>), while lower ALP may indicate reduced vascular inflammation. Maintaining a low level of ALP may exert a protective effect on cognitive function by inhibiting neuroinflammatory responses, without causing significant harm (<xref ref-type="bibr" rid="B57">57</xref>). High alkaline phosphatase (<xref ref-type="bibr" rid="B58">58</xref>) and low albumin were associated with high levels of inflammation (<xref ref-type="bibr" rid="B59">59</xref>). Approximately one-fifth of the dietary fiber-cognitive benefits may be achieved through this inflammatory pathway, while the remaining 80% of the effects may be mediated by other mechanisms such as the gut microbiota/short-chain fatty acids. Moreover, foods rich in fiber are usually rich in anti-inflammatory components such as whole grains, providing a theoretical basis for their substantive mediating role (<xref ref-type="bibr" rid="B60">60</xref>). It is suggested that decreased AAPR indicates the existence of different degrees of malnutrition and inflammation (<xref ref-type="bibr" rid="B61">61</xref>). Therefore, according to the Dietary Guidelines for Americans (2020&#x02013;2025), for older adults whose fiber intake is below the recommended levels (&#x0003C; 22 grams per day for women and &#x0003C; 28 grams per day for men), increasing the fiber intake in their diet to meet these standards may help reduce systemic inflammation and may also lower the risk of cognitive decline.</p>
<p>This study has several notable advantages. Firstly, it was the first study exploring the mediating effect of AAPR on the relationship between dietary fiber intake and cognitive function. Secondly, our study was based on NHANES, a survey that represents the national population. However, there are some limitations in the present study. Firstly, as a cross-sectional study, causation cannot be inferred and there might be a reverse causal relationship. The effect values for some of the associations were relatively small. Future large-scale longitudinal or interventional studies, particularly randomized controlled trials (RCTs), are required to establish causation for the observed associations and to explore their underlying mechanisms. Secondly, the study population was located in the U.S., and the results may not be generalizable to other populations with different dietary habits, genetic backgrounds, or healthcare systems. Thirdly, although we adjusted for key confounders, residual confounding from unmeasured factors may still influence the observed associations. Future research should strive to collect more detailed data on these factors to better control these potential residual confounders. In addition, the assessment of reported dietary fiber intake relied on 24-h recall interviews, which may have been affected by recall bias. Finally, supplements were not considered for this study, which may result in inaccurate calculations of dietary fiber intake.</p></sec>
<sec id="s5">
<title>5 Conclusion</title>
<p>Reported dietary fiber intake, inflammatory markers, and cognitive function were pairwise associated. The AAPR played a mediating role in the association between reported dietary fiber intake and cognitive function.</p></sec>
</body>
<back>
<sec sec-type="data-availability" id="s6">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="supplementary-material" rid="SM1">Supplementary material</xref>, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec sec-type="ethics-statement" id="s7">
<title>Ethics statement</title>
<p>The studies involving humans were approved by National Center for Health Statistics (NCHS) Ethics Review Board (ERB). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.</p>
</sec>
<sec sec-type="author-contributions" id="s8">
<title>Author contributions</title>
<p>KY: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing, Investigation, Formal analysis, Conceptualization. XW: Writing &#x02013; review &#x00026; editing, Writing &#x02013; original draft, Formal analysis, Investigation. FW: Conceptualization, Writing &#x02013; review &#x00026; editing, Investigation. BC: Investigation, Writing &#x02013; review &#x00026; editing. ZZ: Writing &#x02013; review &#x00026; editing. JT: Writing &#x02013; review &#x00026; editing. JZ: Writing &#x02013; review &#x00026; editing. BL: Writing &#x02013; review &#x00026; editing, Supervision, Conceptualization.</p>
</sec>
<sec sec-type="funding-information" id="s9">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research and/or publication of this article.</p>
</sec>
<ack><p>The authors thank the staff and participants of the National Health and Nutrition Examination Survey.</p>
</ack>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="s10">
<title>Generative AI statement</title>
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<title>Publisher&#x00027;s note</title>
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<title>Supplementary material</title>
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<ref-list>
<title>References</title>
<ref id="B1">
<label>1.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Borr&#x000E1;s Blasco</surname> <given-names>C</given-names></name> <name><surname>Vi&#x000F1;a Ribes</surname> <given-names>J</given-names></name></person-group>. <article-title>Neurofisiolog&#x000ED;a Y envejecimiento. Concepto y bases fisiopatol&#x000F3;gicas del deterioro cognitivo</article-title>. <source>Rev Esp Geriatr Gerontol.</source> (<year>2016</year>) <volume>51</volume>:<fpage>3</fpage>&#x02013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1016/S0211-139X(16)30136-6</pub-id><pub-id pub-id-type="pmid">27719970</pub-id></citation></ref>
<ref id="B2">
<label>2.</label>
<citation citation-type="journal"><person-group person-group-type="author"><collab>Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the global burden of disease study 2019</collab></person-group>. <source>Lancet Public Health.</source> (<year>2022</year>) <volume>7</volume>:<fpage>e105</fpage>&#x02013;<lpage>e25</lpage>. <pub-id pub-id-type="doi">10.1016/S2468-2667(21)00249-8</pub-id><pub-id pub-id-type="pmid">34998485</pub-id></citation></ref>
<ref id="B3">
<label>3.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mian</surname> <given-names>M</given-names></name> <name><surname>Tahiri</surname> <given-names>J</given-names></name> <name><surname>Eldin</surname> <given-names>R</given-names></name> <name><surname>Altabaa</surname> <given-names>M</given-names></name> <name><surname>Sehar</surname> <given-names>U</given-names></name> <name><surname>Reddy</surname> <given-names>PH</given-names></name></person-group>. <article-title>Overlooked cases of mild cognitive impairment: implications to early alzheimer&#x00027;s disease</article-title>. <source>Ageing Res Rev.</source> (<year>2024</year>) <volume>98</volume>:<fpage>102335</fpage>. <pub-id pub-id-type="doi">10.1016/j.arr.2024.102335</pub-id><pub-id pub-id-type="pmid">38744405</pub-id></citation></ref>
<ref id="B4">
<label>4.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ag&#x000FC;ero-Torres</surname> <given-names>H</given-names></name> <name><surname>Fratiglioni</surname> <given-names>L</given-names></name> <name><surname>Guo</surname> <given-names>Z</given-names></name> <name><surname>Viitanen</surname> <given-names>M</given-names></name> <name><surname>von Strauss</surname> <given-names>E</given-names></name> <name><surname>Winblad</surname> <given-names>B</given-names></name></person-group>. <article-title>Dementia is the major cause of functional dependence in the elderly: 3-year follow-up data from a population-based study</article-title>. <source>Am J Public Health.</source> (<year>1998</year>) <volume>88</volume>:<fpage>1452</fpage>&#x02013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.2105/AJPH.88.10.1452</pub-id><pub-id pub-id-type="pmid">9772843</pub-id></citation></ref>
<ref id="B5">
<label>5.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hsiao</surname> <given-names>YH</given-names></name> <name><surname>Chang</surname> <given-names>CH</given-names></name> <name><surname>Gean</surname> <given-names>PW</given-names></name></person-group>. <article-title>Impact of social relationships on alzheimer&#x00027;s memory impairment: mechanistic studies</article-title>. <source>J Biomed Sci.</source> (<year>2018</year>) <volume>25</volume>:<fpage>3</fpage>. <pub-id pub-id-type="doi">10.1186/s12929-018-0404-x</pub-id><pub-id pub-id-type="pmid">29325565</pub-id></citation></ref>
<ref id="B6">
<label>6.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Okura</surname> <given-names>M</given-names></name> <name><surname>Ogita</surname> <given-names>M</given-names></name> <name><surname>Arai</surname> <given-names>H</given-names></name></person-group>. <article-title>Self-reported cognitive frailty predicts adverse health outcomes for community-dwelling older adults based on an analysis of sex and age</article-title>. <source>J Nutr Health Aging.</source> (<year>2019</year>) <volume>23</volume>:<fpage>654</fpage>&#x02013;<lpage>64</lpage>. <pub-id pub-id-type="doi">10.1007/s12603-019-1217-7</pub-id><pub-id pub-id-type="pmid">31367731</pub-id></citation></ref>
<ref id="B7">
<label>7.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Sattler</surname> <given-names>C</given-names></name> <name><surname>Toro</surname> <given-names>P</given-names></name> <name><surname>Sch&#x000F6;nknecht</surname> <given-names>P</given-names></name> <name><surname>Schr&#x000F6;der</surname> <given-names>J</given-names></name></person-group>. <article-title>Cognitive activity, education and socioeconomic status as preventive factors for mild cognitive impairment and alzheimer&#x00027;s disease</article-title>. <source>Psychiatry Res.</source> (<year>2012</year>) <volume>196</volume>:<fpage>90</fpage>&#x02013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1016/j.psychres.2011.11.012</pub-id><pub-id pub-id-type="pmid">22390831</pub-id></citation></ref>
<ref id="B8">
<label>8.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname> <given-names>BL</given-names></name> <name><surname>Norhaizan</surname> <given-names>ME</given-names></name></person-group>. <article-title>Effect of high-fat diets on oxidative stress, cellular inflammatory response and cognitive function</article-title>. <source>Nutrients.</source> (<year>2019</year>) <volume>11</volume>:<fpage>2579</fpage>. <pub-id pub-id-type="doi">10.3390/nu11112579</pub-id><pub-id pub-id-type="pmid">31731503</pub-id></citation></ref>
<ref id="B9">
<label>9.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname> <given-names>Y-Y</given-names></name> <name><surname>Zhang</surname> <given-names>M</given-names></name> <name><surname>Wang</surname> <given-names>X-X</given-names></name> <name><surname>Liu</surname> <given-names>S</given-names></name> <name><surname>Ding</surname> <given-names>H</given-names></name></person-group>. <article-title>Correlates of cognitive impairment in the elderly in China: a cross-sectional study</article-title>. <source>Front Public Health.</source> (<year>2022</year>) <volume>10</volume>:<fpage>973661</fpage>. <pub-id pub-id-type="doi">10.3389/fpubh.2022.973661</pub-id><pub-id pub-id-type="pmid">36339179</pub-id></citation></ref>
<ref id="B10">
<label>10.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Prokopidis</surname> <given-names>K</given-names></name> <name><surname>Giannos</surname> <given-names>P</given-names></name> <name><surname>Ispoglou</surname> <given-names>T</given-names></name> <name><surname>Witard</surname> <given-names>OC</given-names></name> <name><surname>Isanejad</surname> <given-names>M</given-names></name></person-group>. <article-title>Dietary fiber intake is associated with cognitive function in older adults: data from the national health and nutrition examination survey</article-title>. <source>Am J Med.</source> (<year>2022</year>) <volume>135</volume>:<fpage>e257</fpage>&#x02013;<lpage>e62</lpage>. <pub-id pub-id-type="doi">10.1016/j.amjmed.2022.03.022</pub-id><pub-id pub-id-type="pmid">35367443</pub-id></citation></ref>
<ref id="B11">
<label>11.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Li</surname> <given-names>F</given-names></name> <name><surname>Chen</surname> <given-names>H</given-names></name> <name><surname>Mao</surname> <given-names>N</given-names></name> <name><surname>Liu</surname> <given-names>H</given-names></name></person-group>. <article-title>Dietary fiber intake and cognitive impairment in older patients with chronic kidney disease in the United States: a cross-sectional study</article-title>. <source>PLoS ONE.</source> (<year>2023</year>) <volume>18</volume>:<fpage>e0291690</fpage>. <pub-id pub-id-type="doi">10.1371/journal.pone.0291690</pub-id><pub-id pub-id-type="pmid">37792684</pub-id></citation></ref>
<ref id="B12">
<label>12.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Uni&#x000F3;n-Caballero</surname> <given-names>A</given-names></name> <name><surname>Mero&#x000F1;o</surname> <given-names>T</given-names></name> <name><surname>Andr&#x000E9;s-Lacueva</surname> <given-names>C</given-names></name> <name><surname>Hidalgo-Liberona</surname> <given-names>N</given-names></name> <name><surname>Rabassa</surname> <given-names>M</given-names></name> <name><surname>Bandinelli</surname> <given-names>S</given-names></name> <etal/></person-group>. <article-title>Apolipoprotein E gene variants shape the association between dietary fibre intake and cognitive decline risk in community-dwelling older adults</article-title>. <source>Age Ageing</source>. (<year>2023</year>) <volume>52</volume>:<fpage>afac329</fpage>. <pub-id pub-id-type="doi">10.1093/ageing/afac329</pub-id><pub-id pub-id-type="pmid">36729469</pub-id></citation></ref>
<ref id="B13">
<label>13.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Naomi</surname> <given-names>R</given-names></name> <name><surname>Teoh</surname> <given-names>SH</given-names></name> <name><surname>Embong</surname> <given-names>H</given-names></name> <name><surname>Balan</surname> <given-names>SS</given-names></name> <name><surname>Othman</surname> <given-names>F</given-names></name> <name><surname>Bahari</surname> <given-names>H</given-names></name> <etal/></person-group>. <article-title>The role of oxidative stress and inflammation in obesity and its impact on cognitive impairments-a narrative review</article-title>. <source>Antioxidants.</source> (<year>2023</year>) <volume>12</volume>:<fpage>1071</fpage>. <pub-id pub-id-type="doi">10.3390/antiox12051071</pub-id><pub-id pub-id-type="pmid">37237937</pub-id></citation></ref>
<ref id="B14">
<label>14.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Balcioglu</surname> <given-names>YH</given-names></name> <name><surname>Kirlioglu</surname> <given-names>SS</given-names></name></person-group>. <article-title>C-Reactive protein/albumin and neutrophil/albumin ratios as novel inflammatory markers in patients with schizophrenia</article-title>. <source>Psychiatry Investig.</source> (<year>2020</year>) <volume>17</volume>:<fpage>902</fpage>&#x02013;<lpage>10</lpage>. <pub-id pub-id-type="doi">10.30773/pi.2020.0185</pub-id><pub-id pub-id-type="pmid">32894927</pub-id></citation></ref>
<ref id="B15">
<label>15.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname> <given-names>RH</given-names></name> <name><surname>Wen</surname> <given-names>WX</given-names></name> <name><surname>Jiang</surname> <given-names>ZP</given-names></name> <name><surname>Du</surname> <given-names>ZP</given-names></name> <name><surname>Ma</surname> <given-names>ZH</given-names></name> <name><surname>Lu</surname> <given-names>AL</given-names></name> <etal/></person-group>. <article-title>The clinical value of neutrophil-to-lymphocyte ratio (Nlr), systemic immune-inflammation index (Sii), platelet-to-lymphocyte ratio (Plr) and systemic inflammation response index (Siri) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage</article-title>. <source>Front Immunol.</source> (<year>2023</year>) <volume>14</volume>:<fpage>1115031</fpage>. <pub-id pub-id-type="doi">10.3389/fimmu.2023.1115031</pub-id><pub-id pub-id-type="pmid">36860868</pub-id></citation></ref>
<ref id="B16">
<label>16.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname> <given-names>X</given-names></name> <name><surname>Xin</surname> <given-names>Y</given-names></name> <name><surname>Chen</surname> <given-names>Y</given-names></name> <name><surname>Zhou</surname> <given-names>X</given-names></name></person-group>. <article-title>Prognostic effect of albumin-to-alkaline phosphatase ratio on patients with hepatocellular carcinoma: a systematic review and meta-analysis</article-title>. <source>Sci Rep.</source> (<year>2023</year>) <volume>13</volume>:<fpage>1808</fpage>. <pub-id pub-id-type="doi">10.1038/s41598-023-28889-2</pub-id><pub-id pub-id-type="pmid">36720974</pub-id></citation></ref>
<ref id="B17">
<label>17.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Qi</surname> <given-names>Q</given-names></name> <name><surname>Zhuang</surname> <given-names>L</given-names></name> <name><surname>Shen</surname> <given-names>Y</given-names></name> <name><surname>Geng</surname> <given-names>Y</given-names></name> <name><surname>Yu</surname> <given-names>S</given-names></name> <name><surname>Chen</surname> <given-names>H</given-names></name> <etal/></person-group>. <article-title>A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy</article-title>. <source>Cancer.</source> (<year>2016</year>) <volume>122</volume>:<fpage>2158</fpage>&#x02013;<lpage>67</lpage>. <pub-id pub-id-type="doi">10.1002/cncr.30057</pub-id><pub-id pub-id-type="pmid">27152949</pub-id></citation></ref>
<ref id="B18">
<label>18.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xiong</surname> <given-names>JP</given-names></name> <name><surname>Long</surname> <given-names>JY</given-names></name> <name><surname>Xu</surname> <given-names>WY</given-names></name> <name><surname>Bian</surname> <given-names>J</given-names></name> <name><surname>Huang</surname> <given-names>HC</given-names></name> <name><surname>Bai</surname> <given-names>Y</given-names></name> <etal/></person-group>. <article-title>Albumin-to-alkaline phosphatase ratio: a novel prognostic index of overall survival in cholangiocarcinoma patients after surgery</article-title>. <source>World J Gastrointest Oncol.</source> (<year>2019</year>) <volume>11</volume>:<fpage>39</fpage>&#x02013;<lpage>47</lpage>. <pub-id pub-id-type="doi">10.4251/wjgo.v11.i1.39</pub-id><pub-id pub-id-type="pmid">30984349</pub-id></citation></ref>
<ref id="B19">
<label>19.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hooper</surname> <given-names>NM</given-names></name> <name><surname>Kellett</surname> <given-names>KAB</given-names></name> <name><surname>Vardy</surname> <given-names>ERLC</given-names></name> <name><surname>Cocklin</surname> <given-names>SL</given-names></name> <name><surname>Smith</surname> <given-names>AD</given-names></name> <name><surname>Williams</surname> <given-names>J</given-names></name></person-group>. <article-title>P2-205: plasma alkaline phosphatase inversely correlates with cognitive function in alzheimer&#x00027;s disease</article-title>. <source>Alzheimers Dement</source>. (<year>2010</year>) 6:S374-S. <pub-id pub-id-type="doi">10.1016/j.jalz.2010.05.1254</pub-id><pub-id pub-id-type="pmid">21686125</pub-id></citation></ref>
<ref id="B20">
<label>20.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname> <given-names>L</given-names></name> <name><surname>Wang</surname> <given-names>F</given-names></name> <name><surname>Liu</surname> <given-names>J</given-names></name> <name><surname>Zhang</surname> <given-names>Q</given-names></name> <name><surname>Lei</surname> <given-names>P</given-names></name></person-group>. <article-title>Inverse relationship between baseline serum albumin levels and risk of mild cognitive impairment in elderly: a seven-year retrospective cohort study</article-title>. <source>Tohoku J Exp Med.</source> (<year>2018</year>) <volume>246</volume>:<fpage>51</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1620/tjem.246.51</pub-id><pub-id pub-id-type="pmid">30249938</pub-id></citation></ref>
<ref id="B21">
<label>21.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Li</surname> <given-names>W</given-names></name> <name><surname>Li</surname> <given-names>S</given-names></name> <name><surname>Shang</surname> <given-names>Y</given-names></name> <name><surname>Zhuang</surname> <given-names>W</given-names></name> <name><surname>Yan</surname> <given-names>G</given-names></name> <name><surname>Chen</surname> <given-names>Z</given-names></name> <etal/></person-group>. <article-title>Associations between dietary and blood inflammatory indices and their effects on cognitive function in elderly Americans</article-title>. <source>Front Neurosci.</source> (<year>2023</year>) <volume>17</volume>:<fpage>1117056</fpage>. <pub-id pub-id-type="doi">10.3389/fnins.2023.1117056</pub-id><pub-id pub-id-type="pmid">36895419</pub-id></citation></ref>
<ref id="B22">
<label>22.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mousa</surname> <given-names>N</given-names></name> <name><surname>Salah</surname> <given-names>M</given-names></name> <name><surname>Elbaz</surname> <given-names>S</given-names></name> <name><surname>Elmetwalli</surname> <given-names>A</given-names></name> <name><surname>Elhammady</surname> <given-names>A</given-names></name> <name><surname>Abdelkader</surname> <given-names>E</given-names></name> <etal/></person-group>. <article-title>Neutrophil percentage-to-albumin ratio is a new diagnostic marker for spontaneous bacterial peritonitis: a prospective multicenter study</article-title>. <source>Gut Pathog.</source> (<year>2024</year>) <volume>16</volume>:<fpage>18</fpage>. <pub-id pub-id-type="doi">10.1186/s13099-024-00610-2</pub-id><pub-id pub-id-type="pmid">38561807</pub-id></citation></ref>
<ref id="B23">
<label>23.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname> <given-names>X</given-names></name> <name><surname>Wen</surname> <given-names>Q</given-names></name> <name><surname>Li</surname> <given-names>Y</given-names></name> <name><surname>Zhu</surname> <given-names>H</given-names></name> <name><surname>Zhang</surname> <given-names>F</given-names></name> <name><surname>Li</surname> <given-names>S</given-names></name> <etal/></person-group>. <article-title>Systemic inflammation markers (Sii and Siri) as predictors of cognitive performance: evidence from nhanes 2011&#x02013;2014</article-title>. <source>Front Neurol.</source> (<year>2025</year>) <volume>16</volume>:<fpage>1527302</fpage>. <pub-id pub-id-type="doi">10.3389/fneur.2025.1527302</pub-id><pub-id pub-id-type="pmid">40417122</pub-id></citation></ref>
<ref id="B24">
<label>24.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Jiang</surname> <given-names>P</given-names></name> <name><surname>Chen</surname> <given-names>J</given-names></name> <name><surname>Li</surname> <given-names>J</given-names></name></person-group>. <article-title>Association of the systemic immune-inflammatory index and systemic inflammatory response index with all-cause and cardiovascular mortality in individuals with metabolic inflammatory syndrome</article-title>. <source>Eur J Med Res.</source> (<year>2025</year>) <volume>30</volume>:<fpage>444</fpage>. <pub-id pub-id-type="doi">10.1186/s40001-025-02611-6</pub-id><pub-id pub-id-type="pmid">40452063</pub-id></citation></ref>
<ref id="B25">
<label>25.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Galland</surname> <given-names>L</given-names></name></person-group>. <article-title>Diet and inflammation</article-title>. <source>Nutr Clin Pract.</source> (<year>2010</year>) <volume>25</volume>:<fpage>634</fpage>&#x02013;<lpage>40</lpage>. <pub-id pub-id-type="doi">10.1177/0884533610385703</pub-id><pub-id pub-id-type="pmid">21139128</pub-id></citation></ref>
<ref id="B26">
<label>26.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Saeed</surname> <given-names>MA</given-names></name> <name><surname>Gribben</surname> <given-names>KC</given-names></name> <name><surname>Alam</surname> <given-names>M</given-names></name> <name><surname>Lyden</surname> <given-names>ER</given-names></name> <name><surname>Hanson</surname> <given-names>CK</given-names></name> <name><surname>LeVan</surname> <given-names>TD</given-names></name></person-group>. <article-title>Association of dietary fiber on asthma, respiratory symptoms, and inflammation in the adult national health and nutrition examination survey population</article-title>. <source>Ann Am Thorac Soc.</source> (<year>2020</year>) <volume>17</volume>:<fpage>1062</fpage>&#x02013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1513/AnnalsATS.201910-776OC</pub-id><pub-id pub-id-type="pmid">32369709</pub-id></citation></ref>
<ref id="B27">
<label>27.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Qi</surname> <given-names>X</given-names></name> <name><surname>Li</surname> <given-names>Y</given-names></name> <name><surname>Fang</surname> <given-names>C</given-names></name> <name><surname>Jia</surname> <given-names>Y</given-names></name> <name><surname>Chen</surname> <given-names>M</given-names></name> <name><surname>Chen</surname> <given-names>X</given-names></name> <etal/></person-group>. <article-title>The associations between dietary fibers intake and systemic immune and inflammatory biomarkers, a multi-cycle study of nhanes 2015&#x02013;2020</article-title>. <source>Front Nutr.</source> (<year>2023</year>) <volume>10</volume>:<fpage>1216445</fpage>. <pub-id pub-id-type="doi">10.3389/fnut.2023.1242115</pub-id><pub-id pub-id-type="pmid">37720377</pub-id></citation></ref>
<ref id="B28">
<label>28.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Shivappa</surname> <given-names>N</given-names></name> <name><surname>Steck</surname> <given-names>SE</given-names></name> <name><surname>Hurley</surname> <given-names>TG</given-names></name> <name><surname>Hussey</surname> <given-names>JR</given-names></name> <name><surname>H&#x000E9;bert</surname> <given-names>JR</given-names></name></person-group>. <article-title>Designing and developing a literature-derived, population-based dietary inflammatory index</article-title>. <source>Public Health Nutr.</source> (<year>2014</year>) <volume>17</volume>:<fpage>1689</fpage>&#x02013;<lpage>96</lpage>. <pub-id pub-id-type="doi">10.1017/S1368980013002115</pub-id><pub-id pub-id-type="pmid">23941862</pub-id></citation></ref>
<ref id="B29">
<label>29.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Marx</surname> <given-names>W</given-names></name> <name><surname>Lane</surname> <given-names>M</given-names></name> <name><surname>Hockey</surname> <given-names>M</given-names></name> <name><surname>Aslam</surname> <given-names>H</given-names></name> <name><surname>Berk</surname> <given-names>M</given-names></name> <name><surname>Walder</surname> <given-names>K</given-names></name> <etal/></person-group>. <article-title>Diet and depression: exploring the biological mechanisms of action</article-title>. <source>Mol Psychiatry.</source> (<year>2021</year>) <volume>26</volume>:<fpage>134</fpage>&#x02013;<lpage>50</lpage>. <pub-id pub-id-type="doi">10.1038/s41380-020-00925-x</pub-id><pub-id pub-id-type="pmid">33144709</pub-id></citation></ref>
<ref id="B30">
<label>30.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Guasch-Ferr&#x000E9;</surname> <given-names>M</given-names></name> <name><surname>Willett</surname> <given-names>WC</given-names></name></person-group>. <article-title>The mediterranean diet and health: a comprehensive overview</article-title>. <source>J Intern Med.</source> (<year>2021</year>) <volume>290</volume>:<fpage>549</fpage>&#x02013;<lpage>66</lpage>. <pub-id pub-id-type="doi">10.1111/joim.13333</pub-id><pub-id pub-id-type="pmid">34423871</pub-id></citation></ref>
<ref id="B31">
<label>31.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Dong</surname> <given-names>X</given-names></name> <name><surname>Li</surname> <given-names>S</given-names></name> <name><surname>Chen</surname> <given-names>J</given-names></name> <name><surname>Li</surname> <given-names>Y</given-names></name> <name><surname>Wu</surname> <given-names>Y</given-names></name> <name><surname>Zhang</surname> <given-names>D</given-names></name></person-group>. <article-title>Association of dietary &#x003A9;-3 and &#x003A9;-6 fatty acids intake with cognitive performance in older adults: national health and nutrition examination survey (Nhanes) 2011-2014</article-title>. <source>Nutr J.</source> (<year>2020</year>) <volume>19</volume>:<fpage>25</fpage>. <pub-id pub-id-type="doi">10.1186/s12937-020-00547-7</pub-id><pub-id pub-id-type="pmid">32222145</pub-id></citation></ref>
<ref id="B32">
<label>32.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Liang</surname> <given-names>X</given-names></name> <name><surname>Lu</surname> <given-names>H</given-names></name> <name><surname>Lin</surname> <given-names>P</given-names></name> <name><surname>Huang</surname> <given-names>X</given-names></name></person-group>. <article-title>Association between dietary fiber to carbohydrate ratio and risk of dental caries in diabetic patients: an analysis of the national health and nutrition examination survey 2015-2020</article-title>. <source>Front Nutr.</source> (<year>2024</year>) <volume>11</volume>:<fpage>1440306</fpage>. <pub-id pub-id-type="doi">10.3389/fnut.2024.1440306</pub-id><pub-id pub-id-type="pmid">39027657</pub-id></citation></ref>
<ref id="B33">
<label>33.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname> <given-names>H</given-names></name> <name><surname>Wei</surname> <given-names>X</given-names></name> <name><surname>Pan</surname> <given-names>J</given-names></name> <name><surname>Chen</surname> <given-names>X</given-names></name> <name><surname>Sun</surname> <given-names>X</given-names></name></person-group>. <article-title>Anemia and frailty in the aging population: implications of dietary fiber intake (findings of the us nhanes from 2007&#x02013;2018)</article-title>. <source>BMC Geriatr.</source> (<year>2023</year>) <volume>23</volume>:<fpage>634</fpage>. <pub-id pub-id-type="doi">10.1186/s12877-023-04352-9</pub-id><pub-id pub-id-type="pmid">37805459</pub-id></citation></ref>
<ref id="B34">
<label>34.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Song</surname> <given-names>W</given-names></name> <name><surname>Feng</surname> <given-names>Y</given-names></name> <name><surname>Gong</surname> <given-names>Z</given-names></name> <name><surname>Tian</surname> <given-names>C</given-names></name></person-group>. <article-title>The association between dietary inflammatory index and cognitive performance in older adults aged 60 years and older</article-title>. <source>Front Nutr.</source> (<year>2022</year>) <volume>9</volume>:<fpage>748000</fpage>. <pub-id pub-id-type="doi">10.3389/fnut.2022.748000</pub-id><pub-id pub-id-type="pmid">35495906</pub-id></citation></ref>
<ref id="B35">
<label>35.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ge</surname> <given-names>S</given-names></name> <name><surname>Dong</surname> <given-names>F</given-names></name> <name><surname>Tian</surname> <given-names>C</given-names></name> <name><surname>Yang</surname> <given-names>C-H</given-names></name> <name><surname>Liu</surname> <given-names>M</given-names></name> <name><surname>Wei</surname> <given-names>J</given-names></name></person-group>. <article-title>Serum soluble alpha-klotho klotho and cognitive functioning in older adults aged 60 and 79: an analysis of cross-sectional data of the national health and nutrition examination survey 2011 to 2014</article-title>. <source>BMC Geriatr.</source> (<year>2024</year>) <volume>24</volume>:<fpage>245</fpage>. <pub-id pub-id-type="doi">10.1186/s12877-024-04661-7</pub-id><pub-id pub-id-type="pmid">38468203</pub-id></citation></ref>
<ref id="B36">
<label>36.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lv</surname> <given-names>JJ</given-names></name> <name><surname>Li</surname> <given-names>XY</given-names></name> <name><surname>Wang</surname> <given-names>JB</given-names></name> <name><surname>Yang</surname> <given-names>XT</given-names></name> <name><surname>Yin</surname> <given-names>MY</given-names></name> <name><surname>Yang</surname> <given-names>CH</given-names></name></person-group>. <article-title>Association of dietary live microbe intake with various cognitive domains in us adults aged 60 years or older</article-title>. <source>Sci Rep.</source> (<year>2024</year>) <volume>14</volume>:<fpage>5714</fpage>. <pub-id pub-id-type="doi">10.1038/s41598-024-51520-x</pub-id><pub-id pub-id-type="pmid">38459061</pub-id></citation></ref>
<ref id="B37">
<label>37.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Li</surname> <given-names>W</given-names></name> <name><surname>Li</surname> <given-names>S</given-names></name> <name><surname>Zhuang</surname> <given-names>W</given-names></name> <name><surname>Shang</surname> <given-names>Y</given-names></name> <name><surname>Yan</surname> <given-names>G</given-names></name> <name><surname>Lu</surname> <given-names>J</given-names></name> <etal/></person-group>. <article-title>Non-linear relationship between dietary vitamin e intake and cognitive performance in older adults</article-title>. <source>Public Health.</source> (<year>2023</year>) <volume>219</volume>:<fpage>10</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1016/j.puhe.2023.03.012</pub-id><pub-id pub-id-type="pmid">37075487</pub-id></citation></ref>
<ref id="B38">
<label>38.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname> <given-names>T</given-names></name> <name><surname>Liu</surname> <given-names>Y</given-names></name> <name><surname>Tian</surname> <given-names>T</given-names></name></person-group>. <article-title>Predicting pathological complete response after neoadjuvant chemotherapy in breast cancer by clinicopathological indicators and ultrasound parameters using a nomogram</article-title>. <source>Sci Rep.</source> (<year>2024</year>) <volume>14</volume>:<fpage>16348</fpage>. <pub-id pub-id-type="doi">10.1038/s41598-024-64766-2</pub-id><pub-id pub-id-type="pmid">39013971</pub-id></citation></ref>
<ref id="B39">
<label>39.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xie</surname> <given-names>H</given-names></name> <name><surname>Wei</surname> <given-names>L</given-names></name> <name><surname>Liu</surname> <given-names>M</given-names></name> <name><surname>Liang</surname> <given-names>Y</given-names></name> <name><surname>Yuan</surname> <given-names>G</given-names></name> <name><surname>Gao</surname> <given-names>S</given-names></name> <etal/></person-group>. <article-title>Neutrophil-albumin ratio as a biomarker for postoperative complications and long-term prognosis in patients with colorectal cancer undergoing surgical treatment</article-title>. <source>Front Nutr.</source> (<year>2022</year>) <volume>9</volume>:<fpage>976216</fpage>. <pub-id pub-id-type="doi">10.3389/fnut.2022.976216</pub-id><pub-id pub-id-type="pmid">36458178</pub-id></citation></ref>
<ref id="B40">
<label>40.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Guo</surname> <given-names>M</given-names></name> <name><surname>Zhu</surname> <given-names>C</given-names></name></person-group>. <article-title>Serum neurofilament light chain, markers of systemic inflammation and clinically relevant depressive symptoms in us adults</article-title>. <source>J Affect Disord.</source> (<year>2024</year>) <volume>363</volume>:<fpage>572</fpage>&#x02013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1016/j.jad.2024.07.146</pub-id><pub-id pub-id-type="pmid">39074516</pub-id></citation></ref>
<ref id="B41">
<label>41.</label>
<citation citation-type="web"><person-group person-group-type="author"><name><surname>2011&#x02013;2012</surname> <given-names>Laboratory Data-Continuous Nhanes</given-names></name></person-group>. Available online at: <ext-link ext-link-type="uri" xlink:href="https://wwwn.cdc.gov/nchs/nhanes/search/datapage.aspx?Component=Laboratory&#x00026;CycleBeginYear=2011">https://wwwn.cdc.gov/nchs/nhanes/search/datapage.aspx?Component=Laboratory&#x00026;CycleBeginYear=2011</ext-link> (Accessed September 20, 2024).</citation>
</ref>
<ref id="B42">
<label>42.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>He</surname> <given-names>Q</given-names></name> <name><surname>An</surname> <given-names>L</given-names></name> <name><surname>Yue</surname> <given-names>Y</given-names></name> <name><surname>Cui</surname> <given-names>C</given-names></name> <name><surname>Wang</surname> <given-names>C</given-names></name> <name><surname>Xu</surname> <given-names>H</given-names></name> <etal/></person-group>. <article-title>Non-linear association between dietary fiber intake and cognitive function mediated by vitamin E: a cross-sectional study in older adults</article-title>. <source>Front Nutr.</source> (<year>2025</year>) <volume>12</volume>:<fpage>1611162</fpage>. <pub-id pub-id-type="doi">10.3389/fnut.2025.1611162</pub-id><pub-id pub-id-type="pmid">40672427</pub-id></citation></ref>
<ref id="B43">
<label>43.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ba</surname> <given-names>DM</given-names></name> <name><surname>Gao</surname> <given-names>X</given-names></name> <name><surname>Al-Shaar</surname> <given-names>L</given-names></name> <name><surname>Muscat</surname> <given-names>JE</given-names></name> <name><surname>Chinchilli</surname> <given-names>VM</given-names></name> <name><surname>Beelman</surname> <given-names>RB</given-names></name> <etal/></person-group>. <article-title>Mushroom intake and depression: a population-based study using data from the US national health and nutrition examination survey (Nhanes), 2005&#x02013;2016</article-title>. <source>J Affect Disord.</source> (<year>2021</year>) <volume>294</volume>:<fpage>686</fpage>&#x02013;<lpage>92</lpage>. <pub-id pub-id-type="doi">10.1016/j.jad.2021.07.080</pub-id><pub-id pub-id-type="pmid">34333177</pub-id></citation></ref>
<ref id="B44">
<label>44.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Butler</surname> <given-names>L</given-names></name> <name><surname>Popkin</surname> <given-names>BM</given-names></name> <name><surname>Poti</surname> <given-names>JM</given-names></name></person-group>. <article-title>Associations of alcoholic beverage consumption with dietary intake, waist circumference and BMI in US adults, Nhanes 2003&#x02013;2012</article-title>. <source>J Acad Nutr Diet</source>. (<year>2018</year>) <volume>118</volume>:<fpage>409</fpage>&#x02013;<lpage>20</lpage>.e3. <pub-id pub-id-type="doi">10.1016/j.jand.2017.09.030</pub-id><pub-id pub-id-type="pmid">29276140</pub-id></citation></ref>
<ref id="B45">
<label>45.</label>
<citation citation-type="web"><person-group person-group-type="author"><collab>US Department of Health and Human Services</collab></person-group>. <source>Dietary Guidelines for Americans, 2020&#x02013;2025</source>. (<year>2020</year>). Available online at: <ext-link ext-link-type="uri" xlink:href="https://health.gov/our-work/nutrition-physical-activity/dietary-guidelines">https://health.gov/our-work/nutrition-physical-activity/dietary-guidelines</ext-link> (Accessed July 22, 2024).</citation>
</ref>
<ref id="B46">
<label>46.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Sun</surname> <given-names>W</given-names></name> <name><surname>Li</surname> <given-names>S</given-names></name> <name><surname>Chen</surname> <given-names>C</given-names></name> <name><surname>Lu</surname> <given-names>Z</given-names></name> <name><surname>Zhang</surname> <given-names>D</given-names></name></person-group>. <article-title>Dietary fiber intake is positively related with cognitive function in US older adults</article-title>. <source>J Funct Foods.</source> (<year>2022</year>) <volume>90</volume>:<fpage>104986</fpage>. <pub-id pub-id-type="doi">10.1016/j.jff.2022.104986</pub-id></citation>
</ref>
<ref id="B47">
<label>47.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname> <given-names>CS</given-names></name></person-group>. <article-title>Roles of diet-associated gut microbial metabolites on brain health: cell-to-cell interactions between gut bacteria and the central nervous system</article-title>. <source>Adv Nutr.</source> (<year>2024</year>) <volume>15</volume>:<fpage>100136</fpage>. <pub-id pub-id-type="doi">10.1016/j.advnut.2023.10.008</pub-id><pub-id pub-id-type="pmid">38436218</pub-id></citation></ref>
<ref id="B48">
<label>48.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gubert</surname> <given-names>C</given-names></name> <name><surname>Kong</surname> <given-names>G</given-names></name> <name><surname>Costello</surname> <given-names>C</given-names></name> <name><surname>Adams</surname> <given-names>CD</given-names></name> <name><surname>Masson</surname> <given-names>BA</given-names></name> <name><surname>Qin</surname> <given-names>W</given-names></name> <etal/></person-group>. <article-title>Dietary fibre confers therapeutic effects in a preclinical model of huntington&#x00027;s disease</article-title>. <source>Brain Behav Immun.</source> (<year>2024</year>) <volume>116</volume>:<fpage>404</fpage>&#x02013;<lpage>18</lpage>. <pub-id pub-id-type="doi">10.1016/j.bbi.2023.12.023</pub-id><pub-id pub-id-type="pmid">38142919</pub-id></citation></ref>
<ref id="B49">
<label>49.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>De Vadder</surname> <given-names>F</given-names></name> <name><surname>Kovatcheva-Datchary</surname> <given-names>P</given-names></name> <name><surname>Goncalves</surname> <given-names>D</given-names></name> <name><surname>Vinera</surname> <given-names>J</given-names></name> <name><surname>Zitoun</surname> <given-names>C</given-names></name> <name><surname>Duchampt</surname> <given-names>A</given-names></name> <etal/></person-group>. <article-title>Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits</article-title>. <source>Cell.</source> (<year>2014</year>) <volume>156</volume>:<fpage>84</fpage>&#x02013;<lpage>96</lpage>. <pub-id pub-id-type="doi">10.1016/j.cell.2013.12.016</pub-id><pub-id pub-id-type="pmid">24412651</pub-id></citation></ref>
<ref id="B50">
<label>50.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Silva</surname> <given-names>YP</given-names></name> <name><surname>Bernardi</surname> <given-names>A</given-names></name> <name><surname>Frozza</surname> <given-names>RL</given-names></name></person-group>. <article-title>The role of short-chain fatty acids from gut microbiota in gut-brain communication</article-title>. <source>Front Endocrinol.</source> (<year>2020</year>) <volume>11</volume>:<fpage>25</fpage>. <pub-id pub-id-type="doi">10.3389/fendo.2020.00025</pub-id><pub-id pub-id-type="pmid">32082260</pub-id></citation></ref>
<ref id="B51">
<label>51.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Niero</surname> <given-names>M</given-names></name> <name><surname>Bartoli</surname> <given-names>G</given-names></name> <name><surname>De Colle</surname> <given-names>P</given-names></name> <name><surname>Scarcella</surname> <given-names>M</given-names></name> <name><surname>Zanetti</surname> <given-names>M</given-names></name></person-group>. <article-title>Impact of dietary fiber on inflammation and insulin resistance in older patients: a narrative review</article-title>. <source>Nutrients.</source> (<year>2023</year>) <volume>15</volume>:<fpage>2365</fpage>. <pub-id pub-id-type="doi">10.3390/nu15102365</pub-id><pub-id pub-id-type="pmid">37242248</pub-id></citation></ref>
<ref id="B52">
<label>52.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bermudez-Brito</surname> <given-names>M</given-names></name> <name><surname>Sahasrabudhe</surname> <given-names>NM</given-names></name> <name><surname>R&#x000F6;sch</surname> <given-names>C</given-names></name> <name><surname>Schols</surname> <given-names>HA</given-names></name> <name><surname>Faas</surname> <given-names>MM</given-names></name> <name><surname>de Vos</surname> <given-names>P</given-names></name></person-group>. <article-title>The impact of dietary fibers on dendritic cell responses <italic>in vitro</italic> is dependent on the differential effects of the fibers on intestinal epithelial cells</article-title>. <source>Mol Nutr Food Res.</source> (<year>2015</year>) <volume>59</volume>:<fpage>698</fpage>&#x02013;<lpage>710</lpage>. <pub-id pub-id-type="doi">10.1002/mnfr.201400811</pub-id><pub-id pub-id-type="pmid">25620425</pub-id></citation></ref>
<ref id="B53">
<label>53.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Medina-Rodriguez</surname> <given-names>EM</given-names></name> <name><surname>Beurel</surname> <given-names>E</given-names></name></person-group>. <article-title>Blood brain barrier and inflammation in depression</article-title>. <source>Neurobiol Dis.</source> (<year>2022</year>) <volume>175</volume>:<fpage>105926</fpage>. <pub-id pub-id-type="doi">10.1016/j.nbd.2022.105926</pub-id><pub-id pub-id-type="pmid">36375722</pub-id></citation></ref>
<ref id="B54">
<label>54.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname> <given-names>Y</given-names></name> <name><surname>Wang</surname> <given-names>Y</given-names></name> <name><surname>Li</surname> <given-names>X</given-names></name> <name><surname>Xie</surname> <given-names>X</given-names></name></person-group>. <article-title>Clinical role of pretreatment albumin-to-alkaline phosphatase ratio in lung cancer: a meta-analysis</article-title>. <source>Sci Rep.</source> (<year>2024</year>) <volume>14</volume>:<fpage>1166</fpage>. <pub-id pub-id-type="doi">10.1038/s41598-024-51844-8</pub-id><pub-id pub-id-type="pmid">38216656</pub-id></citation></ref>
<ref id="B55">
<label>55.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname> <given-names>S</given-names></name> <name><surname>Liu</surname> <given-names>M</given-names></name> <name><surname>Xiang</surname> <given-names>L</given-names></name> <name><surname>Qiu</surname> <given-names>H</given-names></name> <name><surname>Cheng</surname> <given-names>L</given-names></name> <name><surname>Huang</surname> <given-names>Z</given-names></name> <etal/></person-group>. <article-title>tumour burden score combined with albumin-to-alkaline phosphatase ratio predicts prognosis in patients with intrahepatic cholangiocarcinoma</article-title>. <source>J Cell Mol Med.</source> (<year>2024</year>) <volume>28</volume>:<fpage>e18530</fpage>. <pub-id pub-id-type="doi">10.1111/jcmm.18530</pub-id><pub-id pub-id-type="pmid">38961673</pub-id></citation></ref>
<ref id="B56">
<label>56.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wigner</surname> <given-names>P</given-names></name> <name><surname>Czarny</surname> <given-names>P</given-names></name> <name><surname>Galecki</surname> <given-names>P</given-names></name> <name><surname>Su</surname> <given-names>K-P</given-names></name> <name><surname>Sliwinski</surname> <given-names>T</given-names></name></person-group>. <article-title>The molecular aspects of oxidative &#x00026; nitrosative stress and the tryptophan catabolites pathway (trycats) as potential causes of depression</article-title>. <source>Psychiatry Res.</source> (<year>2018</year>) <volume>262</volume>:<fpage>566</fpage>&#x02013;<lpage>74</lpage>. <pub-id pub-id-type="doi">10.1016/j.psychres.2017.09.045</pub-id><pub-id pub-id-type="pmid">28951145</pub-id></citation></ref>
<ref id="B57">
<label>57.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hanley</surname> <given-names>AJ</given-names></name> <name><surname>Williams</surname> <given-names>K</given-names></name> <name><surname>Festa</surname> <given-names>A</given-names></name> <name><surname>Wagenknecht</surname> <given-names>LE</given-names></name> <name><surname>D&#x00027;Agostino RB</surname> <given-names>Jr</given-names></name> <name><surname>Haffner</surname> <given-names>SM</given-names></name></person-group>. <article-title>Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study</article-title>. <source>Diabetes.</source> (<year>2005</year>) <volume>54</volume>:<fpage>3140</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.2337/diabetes.54.11.3140</pub-id><pub-id pub-id-type="pmid">16249437</pub-id></citation></ref>
<ref id="B58">
<label>58.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Seo</surname> <given-names>MS</given-names></name> <name><surname>Shim</surname> <given-names>JY</given-names></name> <name><surname>Lee</surname> <given-names>YJ</given-names></name></person-group>. <article-title>Relationship between serum alkaline phosphatase level, c-reactive protein and leukocyte counts in adults aged 60 years or older</article-title>. <source>Scand J Clin Lab Invest.</source> (<year>2019</year>) <volume>79</volume>:<fpage>233</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1080/00365513.2019.1585567</pub-id><pub-id pub-id-type="pmid">30888211</pub-id></citation></ref>
<ref id="B59">
<label>59.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Don</surname> <given-names>BR</given-names></name> <name><surname>Kaysen</surname> <given-names>G</given-names></name></person-group>. <article-title>Serum albumin: relationship to inflammation and nutrition</article-title>. <source>Semin Dial.</source> (<year>2004</year>) <volume>17</volume>:<fpage>432</fpage>&#x02013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1111/j.0894-0959.2004.17603.x</pub-id><pub-id pub-id-type="pmid">15660573</pub-id></citation></ref>
<ref id="B60">
<label>60.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Milesi</surname> <given-names>G</given-names></name> <name><surname>Rangan</surname> <given-names>A</given-names></name> <name><surname>Grafenauer</surname> <given-names>S</given-names></name></person-group>. <article-title>Whole grain consumption and inflammatory markers: a systematic literature review of randomized control trials</article-title>. <source>Nutrients.</source> (<year>2022</year>) <volume>14</volume>:<fpage>374</fpage>. <pub-id pub-id-type="doi">10.3390/nu14020374</pub-id><pub-id pub-id-type="pmid">35057555</pub-id></citation></ref>
<ref id="B61">
<label>61.</label>
<citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname> <given-names>F</given-names></name> <name><surname>Lu</surname> <given-names>S</given-names></name> <name><surname>Tian</surname> <given-names>M</given-names></name> <name><surname>Hu</surname> <given-names>K</given-names></name> <name><surname>Chen</surname> <given-names>R</given-names></name> <name><surname>Zhang</surname> <given-names>B</given-names></name> <etal/></person-group>. <article-title>Albumin-to-alkaline phosphatase ratio is an independent prognostic indicator in combined hepatocellular and cholangiocarcinoma</article-title>. <source>J Cancer.</source> (<year>2020</year>) <volume>11</volume>:<fpage>5177</fpage>&#x02013;<lpage>86</lpage>. <pub-id pub-id-type="doi">10.7150/jca.45633</pub-id><pub-id pub-id-type="pmid">32742464</pub-id></citation></ref>
</ref-list>
</back>
</article>