Abstract
Background
Dietary fibre and cognitive function are associated with the risk of mortality, respectively. Inadequate dietary fibre intake and cognitive impairment frequently co-occur in older adults, but the combined effect of dietary fibre and cognitive function on mortality remains unknown. The study was to investigate the combined effect of dietary fibre and cognitive function on mortality over a 13-year follow-up in a representative of older adults from the U.S.
Methods
We analyzed data from two cycles of the National Health and Nutrition Examination Survey (NHANES) 1999–2000 and 2001–2002 with mortality follow-up data through 13 December 2015 obtained from Public-use Linked Mortality Files. Low dietary fibre intake was defined as the lowest quartile of dietary fibre intake. Cognitive impairment was defined as below the median of Digit Symbol Substitution Test. The separate and combined effects of low dietary fibre intake and cognitive impairment on all-cause and cause-specific mortality were assessed in older adults using weighted Cox proportional hazard models adjusting for potential confounders.
Results
A total of 2012 participants (weighted sample was 32,765,094) aged 60 years and older were enrolled in the study. After a median follow-up of 13.4 years, 1017 participants (50.4%) were identified as all-cause deaths, including 183 (9.1%) participants dying from cancer, 199 (9.9%) participants dying from cardiovascular disease, and 635 (31.5%) participants dying from non-cancer/non-cardiovascular disease. Participants with low dietary fibre intake and cognitive impairment had nearly twice the risk of all-cause (HR, 2.030; 95% CI, 1.406-2.931) and non-cancer/non-cardiovascular (HR, 2.057; 95% CI, 1.297–3.262) mortality, and over triple cancer (HR, 3.334; 95% CI, 1.685–6.599) mortality, compared to those without both.
Conclusions
The combination of low dietary fibre intake and cognitive impairment was associated with an increased risk of all-cause, cancer and non-cancer/non- cardiovascular mortality in older adults.
The inadequate dietary fibre intake and cognitive impairment often coexist in older adults, but the combined effect of dietary fibre and cognitive function on mortality is still unknown.
This study evaluated the combined effect of dietary fibre and cognitive impairment on mortality among older adults with a 13-year follow-up in the United States, based on the National Health and Nutrition Examination Survey (NHANES).
The results provided evidence of the importance of early screening and intervention for dietary fibre intake and cognitive function, and suggested the joint effect of dietary fibre and cognitive function on mortality could be significant for public health in older adults.
Key Messages
Introduction
With the prolongation of life expectancy, the growing burden of an ageing population has become a global concern. Inadequate dietary fibre intake and cognitive impairment commonly occur in older adults, and are related to an increased risk of mortality, respectively [Citation1,Citation2]. Dietary fibre is one of the key components of a healthy diet [Citation3], accumulating studies have found dietary fibre served as a beneficial diet regulation against several diseases, thereby reducing mortality [Citation4]. The dietary fibre intake decreased with age, and the higher prevalence of inadequate dietary fibre intake was observed in older adults [Citation5]. Cognitive impairment related to aging is a precursor to Alzheimer’s disease (AD) and dementia, and has been a major international public health concern [Citation6]. Many studies have indicated that cognitive impairment is associated with an increased risk of mortality [Citation2,Citation7]. Early recognition and appropriate management of inadequate dietary fibre intake and cognitive impairment should be important to reduce the risk of premature death in older adults.
It was confirmed that diet was closely related to cognitive function [Citation8]. Recent studies have suggested there is an inverse association between dietary fibre intake and the risk of dementia [Citation9,Citation10]. Inadequate dietary fibre intake accompanied with cognitive impairment usually occurs in older adults simultaneously. The associations of dietary fibre and cognitive impairment with mortality were investigated, respectively [Citation4,Citation7]. But it is still unknown that the combined effect of dietary fibre and cognitive impairment on mortality in older adults. Defining the combined effect of dietary fibre and cognitive impairment on mortality may be very important in improving the prognosis of older adults. Therefore, this study evaluated the combined effect of dietary fibre and cognitive impairment on mortality among older adults in the United States with a 13-year follow-up, based on the National Health and Nutrition Examination Survey (NHANES).
Methods
Study design and participants
We analyzed data from two cycles of NHANES 1999–2000 and 2001–2002, a series of nationwide, complex, multistage, and probabilistic sampling design surveys designed to assess U.S. civilians’ health and nutritional status conducted by the National Center for Health Statistics (NCHS). Anonymous data can be obtained publicly from https://www.cdc.gov/nchs/nhanes/index.htm. We linked the data with Public-use Linked Mortality Files (https://www.cdc.gov/nchs/data-linkage/mortality.htm) for follow-up mortality data through 13 December 2015. The survey was conducted in the Mobile Examination Center (MEC) including face-to-face interviews, physical examinations and laboratory tests. Participants aged 60 years and older with dietary fibre intake data and cognitive test (n = 2595) were enrolled in the study. A total of 2012 participants were finally involved into the analysis cohort after excluding those with missing covariates. The NCHS Ethics Review Board approved the study protocol (https://www.cdc.gov/nchs/nhanes/irba98.htm), and all participants provided informed consent.
Cognitive function
The (Digit Symbol Substitution Test) DSST was administered in two cycles of NHANES 1999–2002 to assess cognitive function, which is a widely used, sensitivity method for assessing sustained attention, psychomotor speed, and working memory in Aging’s Health studies [Citation11]. Participants were asked to correctly draw a series of symbols within 2 min. Based on guidelines for scoring the DSST, each participant was given one DSST score (The maximum score is 133) according to the number of correctly matched symbols. The higher score represented better cognitive function. Because there is no recommended cutoff value for DSST score, cognitive impairment was defined as below the median of DSST score (42 scores), as described previously [Citation12,Citation13].
Dietary fibre intake
Dietary intake data were collected by trained interviewers using a 24-h recall survey in the MEC. Dietary fibre intake from all foods and beverages was calculated using the US Department of Agriculture, Food and Nutrient Database for Dietary Studies. Low dietary fibre intake was defined as the lowest quartile of dietary fibre intake in the study, as described previously [Citation1].
Study outcomes
The primary outcome was all-cause mortality. The secondary outcomes included cardiovascular mortality, cancer mortality, and non-cancer/non-cardiovascular mortality. Mortality status and specific causes of death were determined by Public-use Linked Mortality Files. Cardiovascular mortality was defined as death from cardiovascular disease referring to the ICD-10 codes (I00–09, 111, 113, and I20–51). Cancer mortality was defined as death from cancer referring to the ICD-10 codes (C00-C97). Those who were not deceased from the above causes were defined as non-cancer/non-cardiovascular mortality. Follow-up time was calculated from the date of the interview in the MEC to the date of death or the end of the follow-up (December 13, 2015).
Covariates
The sociodemographic information (age, sex, ethnicity, marital status, education, the ratio of income to poverty, smoking status) and medical-related information (Body mass index (BMI), hypertension, diabetes mellitus, high cholesterol, cardiovascular and cancer) were obtained through face-to-face interviews and laboratory tests. Ethnicity was categorized into non-Hispanic White, non-Hispanic Black, other Hispanic, and other race. Marital status was defined as married/with a partner, unmarried and other. Education was categorized into less than 11th grade and high-school grade and above. The ratio of income to poverty was categorized as below poverty (<1.30) and above poverty (≥1.30). Smoking status was defined as non-smoker and smoker. BMI was calculated as weight (Kg) divided by the square of height (m2). Hypertension was defined as self-reported hypertension, systolic blood pressure ≥140 mm Hg or/and diastolic blood pressure ≥90 mm Hg, or reported use of anti-hypertensive medications. Diabetes mellitus was defined as self-reported diabetes, haemoglobin A1c ≥6.5%, fasting plasma glucose level ≥126mg/dl, or reported use of oral glucose-lowering medication or insulin. High cholesterol was defined as total cholesterol ≥240 mg/dl or reported use of the lipid-lowering drug. Cardiovascular disease was defined as a self-reported diagnosis of heart failure, coronary heart disease, angina, heart attack or stroke. Cancer was defined as a self-reported diagnosis of cancer.
Statistical analysis
Due to the complex multistage sampling design of NHANES, all statistical analyses were performed with a sample weight (WTDR4YR) according to the manual of NHANES. All baseline characteristics were expressed as weighted mean (standard deviation) for continuous variables and count (weighted percentage) for categorical variables. Student’s t-test and Rao-Scott chi-square test were applied to compare statistical differences among groups. The associations of low dietary fibre intake and cognitive impairment with all-cause and cause-specific mortality were assessed by weighted Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), respectively. We adjusted for no covariates in crude model, and adjusted for age and sex in model I. Then we further adjusted for more covariates including ethnicity, marital status, education, the ratio of income to poverty, smoking status, BMI, hypertension, diabetes mellitus, high cholesterol, cardiovascular disease, and cancer in model II. To assess the combined effect of low dietary fibre intake and cognitive impairment on mortality, we constructed four-level groups, including no cognitive impairment & high dietary fibre group, only low dietary fibre group, only cognitive impairment group, cognitive impairment & low dietary fibre group. The weighted Kaplan-Meier curves were depicted according to four-level groups, and Log-rank tests were applied for comparing the survival distributions among groups. We also explored the combined effect of low dietary fibre intake and cognitive impairment on mortality by adjusting for multiple covariates. R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria) was performed for all statistical analyses. A two-sided P value of <0.05 was considered statistically significant.
Results
Baseline characteristics of the participants
For the final cohort of 2012 participants (weighted sample was 32,765,094), the average age was 70.24 ± 7.20 years old and 55.2% was female. After a median follow-up of 13.4 years, 1017 (50.4%) participants were identified as all-cause deaths, including 183 (9.1%) participants dying from cancer, 199 (9.9%) participants dying from cardiovascular disease, and 635 (31.5%) participants dying from non-cancer/non-cardiovascular disease. The weighted baseline characteristics grouped by cognitive function were presented in . There were significant differences (p < 0.05) between the participants in terms of all variables, except for sex, BMI, smoking status, high cholesterol, cancer, and dietary fibre intake. And the general characteristics grouped by dietary fibre intake were shown in . Most of variables were statistically different among groups (p < 0.05), except for age, hypertension, diabetes mellitus, high cholesterol, cardiovascular disease, cancer, and DSST score.
Table 1. Sample baseline characteristics by cognitive impairment status of participants (NHANES 1999–2002).
Table 2. Sample baseline characteristics by dietary fibre intake status of participants (NHANES 1999–2002).
Separate association with mortality
presents the separate association of low dietary fibre intake and cognitive impairment with all-cause and cause-specific mortality. After adjusting for covariates in model II, the weighted Cox proportional hazard model indicated that cognitive impairment was associated with poorer survival from all-cause (HR, 1.600; 95% CI, 1.373-1.864), and non-cancer/non-cardiovascular mortality (HR, 1.735; 95% CI, 1.361-2.211). However, we just noted the significant associations of low dietary fibre intake with cancer mortality (HR, 2.045; 95% CI, 1.333–3.136) in Model II.
Table 3. Cox proportional hazards models for all-cause and specific-cause mortality by cognitive or fibre intake status.
Combined effects on mortality
The weighted Kaplan-Meier curves were depicted by four-level groups according to their dietary fibre intake and cognitive function status at baseline ( and ). The Log-rank tests indicated that participants with low dietary fibre intake and cognitive impairment tended to have the highest all-cause and cause-specific mortality.
Figure 1. Kaplan–Meier curves were applied to show all-cause (A) and cardiovascular (B) mortality by cognitive impairment and low dietary fibre intake (NHANES 1999-2002).
Figure 2. Kaplan–Meier curves were applied to show cancer (A) and non-cancer/non- cardiovascular (B) mortality by cognitive impairment and low dietary fibre intake (NHANES 1999-2002).
As shown in , considering no cognitive impairment and high dietary fibre intake group as reference, participants who had low dietary fibre intake but without cognitive impairment showed higher cancer (HR, 2.336; 95% CI, 1.263–4.318) mortality risk; those who had cognitive impairment but with high dietary fibre intake had higher all-cause (HR, 1.509; 95% CI, 1.070–2.129), and non-cancer/non-cardiovascular (HR, 1.573; 95% CI, 1.032–2.399) mortality risk. Furthermore, participants with low dietary fibre intake and cognitive impairment had nearly twofold all-cause (HR, 2.030; 95% CI, 1.406–2.931) and non-cancer/non-cardiovascular (HR, 2.057; 95% CI, 1.297–3.262) mortality risk, and more than triple cancer (HR, 3.334; 95% CI, 1.685–6.599) mortality risk, compared to those without both. However, no significant interaction between dietary fibre intake and cognitive impairment was found (p > 0.05).
Table 4. Cox proportional hazards models of all-cause and specific cause mortality by cognitive and fibre intake status.
Discussion
The prospective cohort study of a nationally representative sample of U.S. older adults with a 13-year follow-up, evaluated the combined effects of dietary fibre and cognitive function on all-cause and cause-specific mortality. The results found that dietary fibre was associated with cancer mortality and cognitive impairment was associated with all-cause and non-cancer/non-cardiovascular mortality, respectively. Compared to older adults with non-impaired cognition and high dietary fibre intake, the older adults with both cognitive impairment and low dietary fibre intake had the highest risk of all-cause, cancer and non-cancer/non-cardiovascular mortality after adjusting for potential confounding factors, but their coexistence was not associated with cardiovascular mortality.
Dietary fibre significantly decreased the risk of chronic diseases such as hypertension, type 2 diabetes, cardiovascular disease and cancers [Citation14–16], all of which are considered the leading causes of death. These studies have indirectly demonstrated that dietary fibre is negatively correlated with mortality. An accumulation of research indicated high dietary fibre intake was associated with reduced mortality risk from all-cause, cardiovascular and cancers [Citation4,Citation15,Citation17]. Our previous study, based on NHANES 2003–2014, suggested high dietary fibre intake significantly decreased all-cause and cardiovascular mortality in older adults with hypertension [Citation1]. The study also confirmed that dietary fibre intake was significantly associated with cancer mortality in older adults, consistent with previous studies [Citation16]. But contrary to these results, the association of dietary fibre with cardiovascular and all-cause mortality were not found in the study. The United Kingdom Women’s Cohort Study found that increased dietary fibre intake did not contribute to a lower risk of cardiovascular mortality [Citation18]. A population-based cohort study of Australia suggested that dietary fibre intake was not associated with cardiovascular mortality in both women (RR:0.88 (95%CI 0.53–1.46)) and men (RR:0.84 (95%CI 0.53–1.34) [Citation19]. Meta-analyses showed the different sources of dietary fibre had different effects on cardiovascular and all-cause mortality [Citation4,Citation14], dietary fibre from cereals was associated with reduced risk of cardiovascular and all-cause mortality, however, fruit fibre was not significantly associated with cardiovascular and all-cause mortality [Citation15]. Differences in assessment methods, a cutoff value, the source and daily dietary fibre intake may affect the role of dietary fibre on cardiovascular and all-cause mortality risk.
The DSST is regarded as one of the most widely used neuropsychological assessment methods in older adults [Citation20]. The DSST provides a better prediction performance of brain dysfunction, and accurately identifies cognitive impairment in older adults [Citation21]. A review found low DSST score was an independent risk factor for mortality in older adults [Citation22]. Older adults with even mild cognitive impairment increased risk of mortality [Citation23]. The mechanism of the relationship between cognitive impairment and mortality remains unclear, but there are potential general explanations for their relationship. People with cognitive impairment may have a worse ability for medical management and self-care, and an unhealthy lifestyle [Citation24]. Cognitive decline in older adults is usually related to vascular cognitive impairments. Vascular cognitive impairments share the same risk factors for cardiovascular disease, such as hypertension, diabetes, smoking, and hyperlipidemia, which would affect health by pathophysiological processes of cardiovascular disease [Citation25].
Previous studies have suggested the different associations of cognitive impairment with mortality according to the cause of mortality [Citation24]. A study found that cognitive impairment reduced the risk of mortality [Citation26], but other previous studies showed the cognitive function was significantly associated with all-cause mortality but not cancer mortality [Citation27,Citation28]. In our study, the negative associations of cognitive function with all-cause and non-cancer/non-cardiovascular mortality were found. These results suggested dietary fibre and cognitive impairment could serve as independent predictors for mortality in older adults, which given evidence to conventional screen dietary fibre intake and cognitive function in older adults.
More significantly, our study found the cognitive impairment accompanied by low dietary fibre intake significantly increased the risk of all-cause mortality, cancer and non-cancer/non-cardiovascular mortality in older adults, compared to only cognitive impairment or low dietary fibre intake. A middle-aged cohort of Australians reported the higher intakes of dietary fibre or multigrain products were related to better cognitive performance [Citation29]. Several studies have suggested older adults with high dietary fibre intake reduce cognitive impairment [Citation30,Citation31]. Clinical evidences showed the richness, diversity and composition of the gut microbiome in individuals with AD and cognitive impairment were significantly different from healthy individuals [Citation32–34], and gut microbiota was associated with AD and cognitive impairment [Citation35,Citation36]. The microbiota-gut-brain axis has received increasing attention recently as a pathogenesis of AD [Citation37]. Dietary fibre interacts with gut microbiota, affects microbial ecology and increases productions of beneficial microbial metabolites, such as short-chain fatty acids, leads to health benefits [Citation3]. Recent studies have shown that dietary fibre may regulate cognition function via the microbiota-gut-brain axis in animal models [Citation38,Citation39]. Some studies have found that older adults with cognitive impairment have more nutritional problems than those who are healthy, people with mild cognitive impairment and early-stage AD had reduced dietary intake due to loss of appetite and apathy [Citation40–42], which may lead to inadequate dietary fibre intake in older adults with cognitive impairment. The relationship between dietary fibre intake and cognitive impairment maybe mutual. Inadequate dietary fibre intake and cognitive impairment are not life-threatening illnesses, but they do increase the risk of death in older adults. In fact, inadequate intake of dietary fibre and cognitive impairment are usually co-occurring in older adults. The public health importance of dietary fibre and cognitive function is widely recognized, but there have been no studies investigating the joint effect of dietary fibre and cognitive function on mortality in older adults. Our study first emphasized the important combination of low dietary fibre intake and cognitive impairment that significantly increased the risk of mortality in older adults, compared with low dietary fibre intake or cognitive impairment alone. Based on this evidence, our results suggest that screening for dietary fibre intake and cognitive function should be included in the public health and management program for older adults. Early identification of inadequate dietary fibre intake and cognitive impairment for positive intervention strategies may decrease the risk of mortality and improve the long-term survival of older adults.
Several limitations still needed to be illustrated in the study. First, dietary fibre intake and cognitive function were only assessed at baseline, the lack of dynamic monitoring during the follow-up period. It is difficult to demonstrate the effects of the changes in dietary fibre intake or cognitive function on mortality, future prospective studies are needed. Second, dietary fibre intake was collected through 24-hour recall, which might cause recall bias and self-report bias. Third, DSST as a single cognitive function test cannot comprehensively assess all areas of cognitive function, other cognitive deficits need to be further studied. Finally, our results may not be generalized to the non-US population and those under the age of 60. Despite its limitations, this study included a large population-based cohort of older adults of NHANES, with long follow-up duration and standardized statistical methods, the results provided a more stable and reliable causal association of the combination of dietary fibre and cognitive function with mortality in older adults.
Conclusion
In conclusion, the study found the older adults with low dietary fibre intake and cognitive impairment had the highest risk of all-cause mortality, cancer and non-cancer/non-cardiovascular mortality. The results provided evidence to support the importance of early screening and intervention for dietary fibre intake and cognitive function, and suggested the joint effect of dietary fibre and cognitive function on mortality may have important public health implications for older adults. Further prospective and intervention studies should be necessary to confirm our findings.
Ethics approval
The survey protocol was approved by NCHS Ethics Review Board (https://www.cdc.gov/nchs/nhanes/irba98.htm), and all participants have written informed consent.
Authors’ contributions
Zhang H participated in the design of this study, acquired data, performed the statistical analysis and drafted the manuscript. Tian W and Qi G participated in its design. Sun Y conceived of the study, and participated in its design and drafting, and provided critical revision for important intellectual content.
Acknowledgement
We would like to thank the data collection team and NHANES administration for the related data available through the NHANES website.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
All data included in this study are from a public NHANES database (https://www.cdc.gov/nchs/nhanes/index.htm), which can be accessed by everyone through the links provided.
Additional information
Funding
References
- Zhang HR, Yang Y, Tian W, et al. Dietary fibre and all-cause and cardiovascular mortality in older adults with hypertension: a cohort study of NHANES. J Nutr Health Aging. 2022;26(4):1–10.
- Perna L, Wahl HW, Mons U, et al. Cognitive impairment, all-cause and cause-specific mortality among non-demented older adults. Age Ageing. 2015;44(3):445–451.
- Barber TM, Kabisch S, Pfeiffer AFH, et al. The health benefits of dietary fibre. Nutrients. 2020;12(10):3209.
- Kim Y, Je Y. Dietary fibre intake and total mortality: a meta-analysis of prospective cohort studies. Am J Epidemiol. 2014;180(6):565–573.
- Silva GMD, Durante ÉB, Assumpção D, et al. High prevalence of inadequate dietary fibre consumption and associated factors in older adults: a population-based study. Brazilian J Epidemiol. 2019;22:e190044.
- Iadecola C, Duering M, Hachinski V, et al. Vascular cognitive impairment and dementia: JACC scientific expert panel. J Am Coll Cardiol. 2019;73(25):3326–3344.
- Sachs GA, Carter R, Holtz LR, et al. Cognitive impairment: an independent predictor of excess mortality: a cohort study. Ann Intern Med. 2011;155(5):300–308.
- Solfrizzi V, Custodero C, Lozupone M, et al. Relationships of dietary patterns, foods, and micro- and macronutrients with Alzheimer’s disease and late-life cognitive disorders: a systematic review. J Alzheimers Dis. 2017;59(3):815–849.
- Cao L, Tan L, Wang HF, et al. Dietary patterns and risk of dementia: a systematic review and meta-analysis of cohort studies. Mol Neurobiol. 2016;53(9):6144–6154.
- Yamagishi K, Maruyama K, Ikeda A, et al. Dietary fibre intake and risk of incident disabling dementia: the circulatory risk in communities study. Nutritional Neuroscience. 2022;6:1–8.
- Wechser. Manual for the wechsler adult intelligence scale-revised. New York: The Psuchological Corporation; 1981.
- Loprinzi PD, Crush E, Joyner C. Cardiovascular disease biomarkers on cognitive function in older adults: Joint effects of cardiovascular disease biomarkers and cognitive function on mortality risk. Prev Med. 2017;94:27–30.
- Liao H, Zhu Z, Wang H, et al. Cognitive performance concomitant with vision acuity predicts 13-year risk for mortality. Front Aging Neurosci. 2019;11:65.
- Yao B, Fang H, Xu W, et al. Dietary fibre intake and risk of type 2 diabetes: a dose-response analysis of prospective studies. Eur J Epidemiol. 2014;29(2):79–88.
- Kim Y, Je Y. Dietary fibre intake and mortality from cardiovascular disease and all cancers: a meta-analysis of prospective cohort studies. Arch Cardiovasc Dis. 2016;109(1):39–54.
- Sun B, Shi X, Wang T, et al. Exploration of the association between dietary fibre intake and hypertension among U.S. Adults using 2017 American college of cardiology/American heart association blood pressure guidelines: NHANES 2007-2014. Nutrients. 2018;10(8):1091.
- Chan CW, Lee PH. Association between dietary fibre intake with cancer and all-cause mortality among 15 740 adults: the national health and nutrition examination survey III. J Hum Nutr Diet. 2016;29(5):633–642.
- Threapleton DE, Greenwood DC, Burley VJ, et al. Dietary fibre and cardiovascular disease mortality in the UK women’s cohort study. Eur J Epidemiol. 2013;28(4):335–346.
- Buyken AE, Flood V, Empson M, et al. Carbohydrate nutrition and inflammatory disease mortality in older adults. Am J Clin Nutr. 2010;92(3):634–643.
- Jaeger J. Digit symbol substitution test: the case for sensitivity over specificity in neuropsychological testing. J Clin Psychopharmacol. 2018;38(5):513–519.
- Tsatali M, Poptsi E, Moraitou D, et al. Discriminant validity of the WAIS-R digit symbol substitution test in subjective cognitive decline, mild cognitive impairment (amnestic subtype) and alzheimer’s disease dementia (ADD) in Greece. Brain Sciences. 2021;11(7):881.
- Rosano C, Newman AB, Katz R, et al. Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults. J Am Geriatr Soc. 2008;56(9):1618–1625.
- Gillum RF, Kwagyan J, Obisesan TO. Smoking, cognitive function and mortality in a U.S. national cohort study. Int J Environ Res Public Health. 2011;8(9):3628–3636.
- Batty GD, Deary IJ, Zaninotto P. Association of cognitive function with cause-specific mortality in middle and older age: follow-up of participants in the english longitudinal study of ageing. Am J Epidemiol. 2016;183(3):183–190.
- Tamosiunas A, Sapranaviciute-Zabazlajeva L, Luksiene D, et al. Cognitive function and mortality: results from Kaunas HAPIEE study 2006-2017. IJERPH. 2020;17(7):2397.
- Benito-León J, Romero JP, Louis ED, et al. Faster cognitive decline in elders without dementia and decreased risk of cancer mortality: NEDICES study. Neurology. 2014;82(16):1441–1448.
- Hagger-Johnson G, Deary IJ, Davies CA, et al. Reaction time and mortality from the major causes of death: the NHANES-III study. PLoS One. 2014;9(1):e82959.
- Yaffe K, Peltz CB, Ewing SK, et al. Long-term cognitive trajectories and mortality in older women. J Gerontol A Biol Sci Med Sci. 2016;71(8):1074–1080.
- Milte CM, Ball K, Crawford D, et al. Diet quality and cognitive function in mid-aged and older men and women. BMC Geriatr. 2019;19(1):361.
- Vercambre MN, Boutron-Ruault MC, Ritchie K, et al. Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly french women. Br J Nutr. 2009;102(3):419–427.
- Aparicio Vizuete A, Robles F, Rodríguez-Rodríguez E, et al. Association between food and nutrient intakes and cognitive capacity in a group of institutionalized elderly people. Eur J Nutr. 2010;49(5):293–300.
- Manderino L, Carroll I, Azcarate-Peril MA, et al. Preliminary evidence for an association between the composition of the gut microbiome and cognitive function in neurologically healthy older adults. J Int Neuropsychol Soc. 2017;23(8):700–705.
- Zhuang ZQ, Shen LL, Li WW, et al. Gut microbiota is altered in patients with Alzheimer’s disease. J Alzheimers Dis. 2018;63(4):1337–1346.
- Nagpal R, Neth BJ, Wang S, et al. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer’s disease markers in subjects with mild cognitive impairment. EBioMedicine. 2019;47:529–542.
- Bonfili L, Cecarini V, Berardi S, et al. Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep. 2017;7(1):2426.
- Zhang L, Wang Y, Xiayu X, et al. Altered gut microbiota in a mouse model of alzheimer’s disease. J Alzheimers Dis. 2017;60(4):1241–1257.
- Askarova S, Umbayev B, Masoud AR, et al. The links between the gut microbiome, aging, modern lifestyle and alzheimer’s disease. Front Cell Infect Microbiol. 2020;10:104.
- Liu X, Li X, Xia B, et al. High-fibre diet mitigates maternal obesity-induced cognitive and social dysfunction in the offspring via gut-brain axis. Cell Metab. 2021;33(5):923–938.e926.
- Shi H, Ge X, Ma X, et al. A fibre-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites. Microbiome. 2021;9(1):223.
- Di Iulio F, Palmer K, Blundo C, et al. Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer’s disease and mild cognitive impairment subtypes. Int Psychogeriatr. 2010;22(4):629–640.
- Suma S, Watanabe Y, Hirano H, et al. Factors affecting the appetites of persons with alzheimer’s disease and mild cognitive impairment. Geriatr Gerontol Int. 2018;18(8):1236–1243.
- Kimura A, Sugimoto T, Kitamori K, et al. Malnutrition is associated with behavioral and psychiatric symptoms of dementia in older women with mild cognitive impairment and Early-Stage alzheimer’s disease. Nutrients. 2019;11(8):1951.