The relationship between micronutrients and cognitive ability in an elderly population with mild cognitive impairment and Alzheimer's disease: a cross-sectional study

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Lifestyle and dietary factors, including micronutrients, have been suggested as modifiable risk factors for disease development. This study aims to investigate the association between micronutrients and cognitive ability in these diseases. Methods : A cross-sectional, randomized controlled study was conducted, involving 105 participants with MCI and AD. Dietary assessments were performed using a validated food frequency questionnaire, and micronutrient intake was calculated based on nutrient content. Disease severity was evaluated using the Functional Assessment Staging Tool (FAST). Statistical analyses, including correlation coefficients and multiple regression models, were employed to examine the association between micronutrients and disease progression. Results : The results revealed significant correlations between disease severity and several micronutrients, including omega-3 fatty acids (B = -0.2, P = 0.01), carotenoids (B = -0.19, P = 0.02), antioxidants (B = -0.19, P = 0.02), selenium (B = -0.17, P = 0.03), alpha-carotene (B = -0.16, P = 0.04), beta-carotene (B = -0.17, P = 0.03), and lycopene (B = -0.16, P = 0.04). Multivariate regression analysis showed that higher intake of omega-3 fatty acids was associated with slower disease progression. Furthermore, the levels of these micronutrients declined in advanced stages of the disease. Conclusion : Omega-3 fatty acids, carotenoids, and antioxidants may affect the cognitive ability and disease progression. Further longitudinal studies are warranted to establish causality and explore the therapeutic implications of these findings for the prevention and management of MCI and AD. Alzheimer's disease dementia micronutrients omega-3 carotenoids antioxidants Introduction Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are two significant neurodegenerative disorders that have a profound impact on individuals and society as a whole [ 1 ]. The prevalence of MCI and AD has been steadily increasing worldwide, posing a significant public health challenge [ 1 ]. According to recent estimates, there were approximately 50 million people living with dementia globally in 2020, with AD accounting for the majority of cases [ 2 ]. Furthermore, both MCI and AD are associated with a higher mortality rate and significantly affect the quality of life for affected individuals and their families [ 3 ]. The financial burden encompasses direct medical expenses, long-term care services, and the indirect costs of caregiving and productivity loss. As the prevalence of these conditions continues to rise, the economic impact on healthcare systems and society as a whole is expected to escalate [ 4 ]. The causes and factors contributing to the development of MCI and AD are complex and multifactorial [ 1 ]. While genetic and environmental factors play a role in disease susceptibility, lifestyle and dietary habits have emerged as potential modifiable risk factors [ 5 ]. Micronutrients, including vitamins, minerals, and antioxidants, have garnered significant attention due to their potential role in neuroprotection and cognitive function [ 6 ]. The absorption and utilization of micronutrients are essential for maintaining brain health and optimal cognitive function [ 6 ]. Deficiencies or imbalances in these micronutrients have been implicated in the pathogenesis of neurodegenerative diseases, including MCI and AD [ 7 ]. Furthermore, the impact of micronutrients extends beyond MCI and AD, as they have been investigated in relation to the prevention and management of various other diseases, including cardiovascular disease, cancer, and age-related macular degeneration [ 8 – 10 ]. Understanding the potential role of micronutrients in neurodegenerative diseases requires careful examination and consideration of the existing scientific evidence [ 7 ]. However, the relationship between micronutrient status and cognitive impairment is still not fully understood, and previous research has yielded conflicting results [ 6 ]. Some studies have reported a positive association between antioxidant micronutrients, such as vitamins A, C, and E, and cognitive function, suggesting that higher intake of these micronutrients may be beneficial for reducing the risk of MCI and AD [ 5 – 7 ]. However, other studies have found no significant association or even contradictory results, indicating that the impact of these antioxidants on cognitive decline may be more complex and multifaceted [ 11 ]. In light of the aforementioned considerations, this article aims to explore the relationship between micronutrients and cognitive ability in an elderly population with MCI and AD. By examining individual diet components rather than overall dietary patterns, this study seeks to shed light on the specific micronutrients that may influence disease progression. Methods Study Design and Participants A cross-sectional, randomized controlled study was conducted between September 2020 and January 2021.The study protocol was in accordance with the Statement on Strengthening Observational Study Reporting in Epidemiology (STROBE) [ 12 ]. The Ethics Committee of the Tehran University of Medical Sciences approved the study (IR.TUMS.MEDICINE.REC.1400.893). Participants were recruited from two memory clinics in the Department of Cognitive Neurology and Neuropsychiatry of Roozbeh Hospital and the Department of Geriatrics of Ziaeian Hospital both affiliated with Tehran University of Medical Sciences. The inclusion criteria were as follows: individuals aged 60 years or older, the permission from the patient’s caregivers, and willingness to participate. Patients with Alzheimer's disease (AD) who had confounding underlying conditions, such as another neurodegenerative disease, anoxic brain injury, stroke, or inability to understand or speak Persian, were excluded from the study. The second researcher assessed the eligibility of participants, and informed consent was obtained from the caregivers before participation. Anthropometric Assessments Anthropometric measurements were performed according to the methodology provided by the World Health Organization [ 13 ]. The Seca Clara 803 digital hand scale with an accuracy of 0.01 grams was used for weighing. Height was measured using a shoeless Seca (Stadiometer) with a sensitivity of 0.1 cm (Seca, Germany). Participants body mass index is also calculated using the appropriate formula (BMI= (weight (kg))/ (height (m 2 )). Dementia Assessment The diagnosis of Alzheimer's disease (AD) was based on the NINCDS–ADRDA (National Institute of Neurological and Communicative Disorders, Stroke-Alzheimer's Disease and Related Disorders Association) criteria [ 14 ]. Mild cognitive impairment (MCI) was diagnosed according to standard research criteria [ 15 ]. The severity and extent of Alzheimer's disease progression were assessed using the Functional Assessment Staging Tool (FAST), a reliable method for evaluating performance deterioration in Alzheimer's patients [ 16 ]. The Persian version of FAST was used, which recognizes seven progressive stages of cognitive decline in Alzheimer's disease. Dietary Assessment Participants completed a 142-item Willett-format dish-based semi-quantitative food frequency questionnaire (FFQ) specifically developed and validated for Iranian adults [ 17 , 18 ]. The FFQ covered various foods and dishes in the typical Iranian diet. Each food item had nine frequency response options, and portion sizes were also recorded. Based on the FFQ, daily nutrient intake was calculated by multiplying the consumption frequency of each food item by the nutrient content. Nutrient intakes were calculated based on the US Department of Agriculture (USDA) national nutrient database and Iran's Food Composition Table [ 19 , 20 ]. To adjust for total caloric intake, linear regression models were used to calculate the residuals of nutrient intake. These residuals were standardized and used for all subsequent analyses. Covariate Assessment Sociodemographic and lifestyle characteristics were assessed as potential confounders. These included age, gender, race/ethnicity, marital status, years of education, body mass index (BMI), drug abuse, and smoking status. The Charlson Comorbidity Index, which includes information on various medical conditions, was used to assess comorbidities [ 21 ]. Physical activity was assessed using the Godin leisure-time exercise questionnaire, and a summary physical activity score was calculated [ 22 ]. Statistical Analysis Continuous variables were presented as mean ± standard deviation (SD), while categorical variables were described as frequency and percentage. Spearman's rank correlation coefficient was used to assess the association between micronutrient intake and dementia progression, with adjustments made for calorie intake. Multiple regression analyses were conducted to predict the progression of dementia, considering linearity, independence of residuals, homoscedasticity, and multicollinearity. According to Cohen 1988, the effect size of correlations was interpreted as small (0.1– 0.3), medium (0.3–0.5) or large (> 0.5) [ 23 ]. The statistical analysis was performed using SPSS version 26, and a p-value of < 0.05 was considered statistically significant. Results A total of 105 participants with cognitive impairment and Alzheimer's disease were included in the study. The distribution of participants according to disease severity was as follows: Mild Cognitive Impairment (MCI) (n = 24), mild dementia (n = 46), moderate dementia (n = 15), and moderately severe dementia (n = 20). In the Alzheimer's disease group, there were 54 male patients and 51 female patients, and in the MCI group, there were 23 patients of both sexes. The mean body mass index (BMI) of the patients was 25.9, indicating an overall average weight status within the normal range. Among the different severity groups, the Moderately Severe Dementia group exhibited the highest BMI, with a mean value of 26.8 (Figure ) . The mean age of the patients was 74.1 years, reflecting an elderly population. Among the severity groups, the Moderate Dementia group had the highest mean age, with an average of 76.2 years. The average caloric intake of the patients was 1600 kcal/day ( Fig. 2 ) . When comparing the severity groups, both the Mild Dementia and Moderately Severe Dementia groups had the highest caloric intake, averaging at 1676 kcal/day. The association between dietary factors and the severity of Alzheimer's disease was analyzed. Among the dietary factors, several micronutrients showed significant correlations with disease severity. Omega-3 fatty acids (B = -0.2, P = 0.01), carotenoids (B = -0.19, P = 0.02), and antioxidants (carotenoids, vitamins A, C, D, E, and selenium) (B = -0.19, P = 0.02) were negatively correlated with disease severity ( Table 1 ) . Additionally, selenium (B = -0.17, P = 0.03), alpha-carotene (B = -0.16, P = 0.04), beta-carotene (B = -0.17, P = 0.03), and lycopene (B = -0.16, P = 0.04) were also negatively correlated with disease severity ( Table 2 ) . Further analysis using multivariate regression revealed that only omega-3 fatty acid intake (Standardized beta = -0.21, P-value = 0.03) significantly predicted the progression of the disease. Table 1 The correlation of micronutrients with disease progression is based on Spearman's correlation. * P < 0.05, MUFA: monounsaturated fatty acids, PUFA: polyunsaturated fatty acids, Total carotenoids: B-carotene, A-carotene, lutein + zeaxanthin, A-cryptoxanthin, and lycopene, Antioxidants: carotenoids, antioxidant vitamins (vitamins A, C, D, E), and selenium. OMEGA 3 OMEGA 6 MUFA PUFA Anti-Oxidants carotenoids Selenium Correlation − .204 − .031 .035 − .065 − .199 − .195 − .173 Significance .019 * .378 .363 .257 .022 * .024 * .039 * Vitamin B6 Vitamin B9 Vitamin B12 Vitamin E Vitamin D Vitamin C Vitamin A Correlation -0.12 − .127 .005 − .071 − .047 − .071 − .159 Significance 0.1 .100 .479 .236 .318 .236 .053 B-Carotene Lycopene Lutein & zeaxanthin alpha-Carotene beta-cryptoxanthin Correlation − .179 − .164 .081 − .167 − .011 Significance .035 * .048 * .207 .045 * .457 Table 2 Analysis of multivariate regression to predict disease progression by micronutrients after adjusting dietary variables for calorie intake. *P < 0.05. Variable beta coefficient Significance MUFA 0.186 0.551 PUFA -0.867 0.319 Vitamin A 0.700 0.280 Vitamin E 0.577 0.530 Vitamin D -0.101 0.496 Vitamin C -0.161 0.501 Vitamin B9 -0.242 0.328 Vitamin B12 0.106 0.507 Vitamin B6 0.147 0.4 B-Carotene -0.019 0.978 OMEGA 3 -0.219 0.038 * OMEGA 6 -0.020 0.979 Selenium -0.146 0.166 alpha-Carotene -0.905 0.182 beta-Cryptoxanthin 0.217 0.261 Lycopene -0.217 0.099 Luteinzeaxanthin 0.077 0.643 Discussion The present study investigated the relationship between individual dietary components and cognitive decline in elderly patients with MCI and AD. The findings revealed several important associations between micronutrient intake and the progression and severity of the disease. Omega-3 fatty acids, carotenoids, and antioxidants, including vitamins A, C, D, E, and selenium, were found to be negatively correlated with disease severity. Moreover, selenium, alpha-carotene, beta-carotene, and lycopene levels declined in the more advanced stages of Alzheimer's disease. Interestingly, after adjusting for energy intake, only omega-3 fatty acid intake significantly predicted the progression of the disease. These findings are consistent with previous research that has investigated the impact of nutrition on cognitive function and Alzheimer's disease. Recent animal studies have shown that lycopene has protective properties by reducing oxidative stress, suppressing the production of inflammatory cytokines, and preventing the accumulation of amyloid plaques [ 24 – 27 ]. In addition, according to animal experiments, selenium-containing compounds influence the metabolism of neurotransmitters. However, the most important involvement of selenium in AD is the antioxidant function of various selenium-dependent enzymes[ 28 ]. Several studies have shown that Omega-3 fatty acids are associated with improved memory and reduced risk of Alzheimer's disease in the elderly [ 29 ]. Recently, beta-carotene has been shown to have a protective effect against oxidative stress and reduce AD risk .one study evaluated the effects of a beta-carotene-rich diet versus supplements on the risk of developing AD and found that it could significantly reduce its risk [ 30 ]. Several studies have shown that the carotene in fruits and vegetables can protect brain tissue from free radical damage, thereby improving cognitive function and memory [ 31 ]. Fat-soluble vitamins A, D, and E are considered antioxidants with potential benefits. In some studies, the serum levels of these vitamins were reduced in AD patients compared to healthy individuals [ 32 ]. However, conflicting findings have been reported when examining the association between cognitive function or dementia and the consumption of certain antioxidants in fruits and vegetables, including beta-carotene, vitamins C and E, and flavonoids [ 11 ]. the results suggest that micronutrients, specifically omega-3 fatty acids, carotenoids, antioxidants, selenium, alpha-carotene, beta-carotene, and lycopene, play a crucial role in the progression and severity of AD in elderly individuals with mild cognitive impairment and AD. The negative correlations observed between these dietary factors and disease severity indicate that lower levels of these micronutrients are associated with more advanced stages of AD. The mechanism behind these associations can be attributed to the beneficial effects of these nutrients on brain health. Omega-3 fatty acids, particularly DHA, have positive effects on the regulation of inflammatory processes. They influence the inflammatory response by altering the structure and properties of cell membranes through their direct impact on receptor function and the activity of ion channels involved in immune activation. Recent research has indicated that a lack of production of anti-inflammatory substances plays a significant role in cognitive decline among patients with AD. Additionally, findings from epidemiological studies suggest the presence of a crucial period of at least two years prior to dementia onset in which there is an increase in proinflammatory substances in the brain, potentially influencing the progression of AD [ 33 ]. In light of these findings, researchers, propose that omega-3 supplementation may have preventive or disease-slowing benefits, but it may not be effective in treating dementia once it has already developed [ 34 ]. Although the relationship between the characteristic lesions of AD pathology, such as B-amyloid and tau proteins, and oxidative stress is still not fully understood, there is a growing body of evidence suggesting that oxidative stress and the generation of free radicals play a role in the progression of cellular injury and death, which contributes to the development of neurodegenerative diseases [ 35 , 36 ]. Therefore, therapeutic interventions aimed at inhibiting oxidative stress, such as the use of antioxidant nutrients, may be beneficial in interrupting the cycle of cell death. In AD, oxidative stress is not only elevated but also persistent, and it occurs within an environment that becomes more susceptible to damage as a person ages. In addition to its involvement in AD pathology, oxidative stress has also been identified as a critical component in various steps of atherosclerosis and acute thrombotic events. These include dyslipidemia, the formation of atheroma, the oxidation of low-density lipoproteins, endothelial damage, plaque rupture, myocardial ischemic injury, and recurrent thrombosis. These pathways may be associated with the development and progression of vascular cognitive impairment and dementia. Therefore, the intake of dietary antioxidants can reduce the progress of cognitive decline in Alzheimer's by reducing oxidative stress [ 37 ]. The decline in these micronutrients in more advanced stages of AD may be due to various factors. Neuroinflammation and increased metabolic demands in AD can lead to increased oxidative stress and nutrient depletion. Additionally, changes in appetite, dietary patterns, and nutrient absorption associated with cognitive impairment may contribute to inadequate intake of these essential micronutrients. The study's strengths lie in its rigorous methodology, including a well-defined participant selection process, the use of validated assessment tools for dementia diagnosis and severity, and a comprehensive dish-based food frequency questionnaire for dietary assessment. Additionally, the study adjusted for potential confounding factors and applied appropriate statistical analyses to evaluate the correlations. However, some limitations should be acknowledged, such as the cross-sectional design, which limits causal inference, and the reliance on self-reported dietary data, which may be subject to recall bias, and the study was conducted in a specific population in Iran, which may limit the generalizability of the findings to other populations. Conclusion Certain micronutrients, specifically omega-3 fatty acids, carotenoids, and antioxidants, may play a role in disease progression. Higher intake of omega-3 fatty acids was associated with slower disease progression in AD patients. Furthermore, the levels of these micronutrients declined in the more advanced stages of the disease, indicating their potential involvement in the pathogenesis and progression of AD. These results highlight the importance of considering individual dietary components and incorporating micronutrients into the diet of elderly individuals with cognitive impairment and AD. However, it is important to note that this study was cross-sectional in nature, and further longitudinal studies are needed to establish a causal relationship and determine the optimal intake of these micronutrients for disease management and prevention. Declarations Acknowledgements Not applicable. Authors’ contributions ZV and RH contributed in conception, design, statistical analyses, data interpretation and manuscript drafting. CA, AR, HH, and MA contributed in data collection, interpretation and manuscript drafting. FE, DF and HR contributed to the data analysis and approving the final manuscript. ZV supervised the study. All authors contributed to the article and approved the submitted version. Funding No financial support was provided in any way for this research. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available, but are available from the corresponding author at reasonable request. Ethics approval and consent to participate The Ethics Committee of the Tehran University of Medical Sciences approved the study (IR.TUMS.MEDICINE.REC.1400.893). The legal guardians of the individuals signed an informed written consent. Consent for publication Not applicable. Competing interests Authors declare no competing interests. Author details 1 Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. 2 Department of Geriatric Medicine, Ziaeian Hospital, Tehran University of Medical Sciences, Tehran, Iran 3 Department of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 Department of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran 5 Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran 6 Department of Psychiatry, Psychosomatic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran 7 Department of Emergency Medicine, faculty of medicine, Tehran University of medical sciences, Tehran, Iran 8 Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran 9 Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada 10 Cognitive Neurology and Neuropsychiatry Division, Psychiatry Department, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. 11 Geriatric Department, Ziaeeian Hospital, Tehran University of Medical Sciences, Tehran, Iran. 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Cite Share Download PDF Status: Published Journal Publication published 25 Oct, 2024 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 30 Jul, 2024 Reviews received at journal 26 Jul, 2024 Reviewers agreed at journal 26 Jul, 2024 Reviewers agreed at journal 22 Jul, 2024 Reviewers agreed at journal 22 Jul, 2024 Reviews received at journal 21 Jul, 2024 Reviewers agreed at journal 20 Jul, 2024 Reviewers invited by journal 20 Jul, 2024 Editor invited by journal 30 Apr, 2024 Editor assigned by journal 29 Apr, 2024 Submission checks completed at journal 29 Apr, 2024 First submitted to journal 07 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4231202","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":297485141,"identity":"20baa29e-f614-4f4f-be01-4a41334788e4","order_by":0,"name":"Camellia Akhgarjand","email":"data:image/png;base64,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","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Camellia","middleName":"","lastName":"Akhgarjand","suffix":""},{"id":297485143,"identity":"fd9d7503-2c18-46da-912f-a8767b0a129c","order_by":1,"name":"Rezvan Hashemi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Rezvan","middleName":"","lastName":"Hashemi","suffix":""},{"id":297485145,"identity":"cd0d62d6-fc6b-4351-896b-3285058d22e9","order_by":2,"name":"Maryam Amini","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Maryam","middleName":"","lastName":"Amini","suffix":""},{"id":297485147,"identity":"28f3d41c-0b27-4a4b-8fed-7add7119889f","order_by":3,"name":"Hamid Rasekhi","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hamid","middleName":"","lastName":"Rasekhi","suffix":""},{"id":297485152,"identity":"44e9bc4e-ffdb-41c2-997e-ab9be1ac2d1f","order_by":4,"name":"Dorreh Farazandeh","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Dorreh","middleName":"","lastName":"Farazandeh","suffix":""},{"id":297485157,"identity":"aea66abc-6cd2-42f4-8423-cd0e829dbea5","order_by":5,"name":"Farnaz Etesam","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Farnaz","middleName":"","lastName":"Etesam","suffix":""},{"id":297485161,"identity":"67419eb3-ae58-4bf2-8f94-6f153feb571d","order_by":6,"name":"Aziz Rasooli","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Aziz","middleName":"","lastName":"Rasooli","suffix":""},{"id":297485165,"identity":"5a772be4-fa64-47c0-81d4-265e97b7cecb","order_by":7,"name":"Hirad Houjaghani","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hirad","middleName":"","lastName":"Houjaghani","suffix":""},{"id":297485169,"identity":"2793682c-aa55-4aeb-884f-ad74a748967a","order_by":8,"name":"Sholeh Faezi","email":"","orcid":"","institution":"Western University","correspondingAuthor":false,"prefix":"","firstName":"Sholeh","middleName":"","lastName":"Faezi","suffix":""},{"id":297485174,"identity":"4350fb58-f3a0-44bc-9ffe-3a5944745ec2","order_by":9,"name":"Zahra Vahabi","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zahra","middleName":"","lastName":"Vahabi","suffix":""}],"badges":[],"createdAt":"2024-04-07 11:59:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4231202/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4231202/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-024-03800-2","type":"published","date":"2024-10-25T15:57:44+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67682403,"identity":"2f1cca7c-c554-4712-8fcd-a2f7d575681b","added_by":"auto","created_at":"2024-10-28 16:13:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":494197,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4231202/v1/9fd62b7c-e68b-4555-a029-e09789bacec7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The relationship between micronutrients and cognitive ability in an elderly population with mild cognitive impairment and Alzheimer's disease: a cross-sectional study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMild cognitive impairment (MCI) and Alzheimer's disease (AD) are two significant neurodegenerative disorders that have a profound impact on individuals and society as a whole [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The prevalence of MCI and AD has been steadily increasing worldwide, posing a significant public health challenge [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. According to recent estimates, there were approximately 50\u0026nbsp;million people living with dementia globally in 2020, with AD accounting for the majority of cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Furthermore, both MCI and AD are associated with a higher mortality rate and significantly affect the quality of life for affected individuals and their families [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The financial burden encompasses direct medical expenses, long-term care services, and the indirect costs of caregiving and productivity loss. As the prevalence of these conditions continues to rise, the economic impact on healthcare systems and society as a whole is expected to escalate [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe causes and factors contributing to the development of MCI and AD are complex and multifactorial [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. While genetic and environmental factors play a role in disease susceptibility, lifestyle and dietary habits have emerged as potential modifiable risk factors [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Micronutrients, including vitamins, minerals, and antioxidants, have garnered significant attention due to their potential role in neuroprotection and cognitive function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The absorption and utilization of micronutrients are essential for maintaining brain health and optimal cognitive function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Deficiencies or imbalances in these micronutrients have been implicated in the pathogenesis of neurodegenerative diseases, including MCI and AD [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Furthermore, the impact of micronutrients extends beyond MCI and AD, as they have been investigated in relation to the prevention and management of various other diseases, including cardiovascular disease, cancer, and age-related macular degeneration [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Understanding the potential role of micronutrients in neurodegenerative diseases requires careful examination and consideration of the existing scientific evidence [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, the relationship between micronutrient status and cognitive impairment is still not fully understood, and previous research has yielded conflicting results [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Some studies have reported a positive association between antioxidant micronutrients, such as vitamins A, C, and E, and cognitive function, suggesting that higher intake of these micronutrients may be beneficial for reducing the risk of MCI and AD [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, other studies have found no significant association or even contradictory results, indicating that the impact of these antioxidants on cognitive decline may be more complex and multifaceted [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn light of the aforementioned considerations, this article aims to explore the relationship between micronutrients and cognitive ability in an elderly population with MCI and AD. By examining individual diet components rather than overall dietary patterns, this study seeks to shed light on the specific micronutrients that may influence disease progression.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e \u003cp\u003eA cross-sectional, randomized controlled study was conducted between September 2020 and January 2021.The study protocol was in accordance with the Statement on Strengthening Observational Study Reporting in Epidemiology (STROBE) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The Ethics Committee of the Tehran University of Medical Sciences approved the study (IR.TUMS.MEDICINE.REC.1400.893).\u003c/p\u003e \u003cp\u003eParticipants were recruited from two memory clinics in the Department of Cognitive Neurology and Neuropsychiatry of Roozbeh Hospital and the Department of Geriatrics of Ziaeian Hospital both affiliated with Tehran University of Medical Sciences. The inclusion criteria were as follows: individuals aged 60 years or older, the permission from the patient\u0026rsquo;s caregivers, and willingness to participate. Patients with Alzheimer's disease (AD) who had confounding underlying conditions, such as another neurodegenerative disease, anoxic brain injury, stroke, or inability to understand or speak Persian, were excluded from the study. The second researcher assessed the eligibility of participants, and informed consent was obtained from the caregivers before participation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eAnthropometric Assessments\u003c/h2\u003e \u003cp\u003eAnthropometric measurements were performed according to the methodology provided by the World Health Organization [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The Seca Clara 803 digital hand scale with an accuracy of 0.01 grams was used for weighing. Height was measured using a shoeless Seca (Stadiometer) with a sensitivity of 0.1 cm (Seca, Germany). Participants body mass index is also calculated using the appropriate formula (BMI= (weight (kg))/ (height (m\u003csup\u003e2\u003c/sup\u003e)).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDementia Assessment\u003c/h2\u003e \u003cp\u003eThe diagnosis of Alzheimer's disease (AD) was based on the NINCDS\u0026ndash;ADRDA (National Institute of Neurological and Communicative Disorders, Stroke-Alzheimer's Disease and Related Disorders Association) criteria [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Mild cognitive impairment (MCI) was diagnosed according to standard research criteria [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The severity and extent of Alzheimer's disease progression were assessed using the Functional Assessment Staging Tool (FAST), a reliable method for evaluating performance deterioration in Alzheimer's patients [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The Persian version of FAST was used, which recognizes seven progressive stages of cognitive decline in Alzheimer's disease.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eDietary Assessment\u003c/h2\u003e \u003cp\u003eParticipants completed a 142-item Willett-format dish-based semi-quantitative food frequency questionnaire (FFQ) specifically developed and validated for Iranian adults [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The FFQ covered various foods and dishes in the typical Iranian diet. Each food item had nine frequency response options, and portion sizes were also recorded. Based on the FFQ, daily nutrient intake was calculated by multiplying the consumption frequency of each food item by the nutrient content. Nutrient intakes were calculated based on the US Department of Agriculture (USDA) national nutrient database and Iran's Food Composition Table [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. To adjust for total caloric intake, linear regression models were used to calculate the residuals of nutrient intake. These residuals were standardized and used for all subsequent analyses.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eCovariate Assessment\u003c/h2\u003e \u003cp\u003eSociodemographic and lifestyle characteristics were assessed as potential confounders. These included age, gender, race/ethnicity, marital status, years of education, body mass index (BMI), drug abuse, and smoking status. The Charlson Comorbidity Index, which includes information on various medical conditions, was used to assess comorbidities [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Physical activity was assessed using the Godin leisure-time exercise questionnaire, and a summary physical activity score was calculated [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), while categorical variables were described as frequency and percentage. Spearman's rank correlation coefficient was used to assess the association between micronutrient intake and dementia progression, with adjustments made for calorie intake. Multiple regression analyses were conducted to predict the progression of dementia, considering linearity, independence of residuals, homoscedasticity, and multicollinearity. According to Cohen 1988, the effect size of correlations was interpreted as small (0.1\u0026ndash; 0.3), medium (0.3\u0026ndash;0.5) or large (\u0026gt;\u0026thinsp;0.5) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The statistical analysis was performed using SPSS version 26, and a p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 105 participants with cognitive impairment and Alzheimer's disease were included in the study. The distribution of participants according to disease severity was as follows: Mild Cognitive Impairment (MCI) (n\u0026thinsp;=\u0026thinsp;24), mild dementia (n\u0026thinsp;=\u0026thinsp;46), moderate dementia (n\u0026thinsp;=\u0026thinsp;15), and moderately severe dementia (n\u0026thinsp;=\u0026thinsp;20). In the Alzheimer's disease group, there were 54 male patients and 51 female patients, and in the MCI group, there were 23 patients of both sexes. The mean body mass index (BMI) of the patients was 25.9, indicating an overall average weight status within the normal range. Among the different severity groups, the Moderately Severe Dementia group exhibited the highest BMI, with a mean value of 26.8 \u003cb\u003e(Figure )\u003c/b\u003e. The mean age of the patients was 74.1 years, reflecting an elderly population. Among the severity groups, the Moderate Dementia group had the highest mean age, with an average of 76.2 years. The average caloric intake of the patients was 1600 kcal/day \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. When comparing the severity groups, both the Mild Dementia and Moderately Severe Dementia groups had the highest caloric intake, averaging at 1676 kcal/day.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe association between dietary factors and the severity of Alzheimer's disease was analyzed. Among the dietary factors, several micronutrients showed significant correlations with disease severity. Omega-3 fatty acids (B = -0.2, P\u0026thinsp;=\u0026thinsp;0.01), carotenoids (B = -0.19, P\u0026thinsp;=\u0026thinsp;0.02), and antioxidants (carotenoids, vitamins A, C, D, E, and selenium) (B = -0.19, P\u0026thinsp;=\u0026thinsp;0.02) were negatively correlated with disease severity \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Additionally, selenium (B = -0.17, P\u0026thinsp;=\u0026thinsp;0.03), alpha-carotene (B = -0.16, P\u0026thinsp;=\u0026thinsp;0.04), beta-carotene (B = -0.17, P\u0026thinsp;=\u0026thinsp;0.03), and lycopene (B = -0.16, P\u0026thinsp;=\u0026thinsp;0.04) were also negatively correlated with disease severity \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Further analysis using multivariate regression revealed that only omega-3 fatty acid intake (Standardized beta = -0.21, P-value\u0026thinsp;=\u0026thinsp;0.03) significantly predicted the progression of the disease.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe correlation of micronutrients with disease progression is based on Spearman's correlation.\u003cem\u003e*\u003c/em\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.05, MUFA: monounsaturated fatty acids, PUFA: polyunsaturated fatty acids, Total carotenoids: B-carotene, A-carotene, lutein\u0026thinsp;+\u0026thinsp;zeaxanthin, A-cryptoxanthin, and lycopene, Antioxidants: carotenoids, antioxidant vitamins (vitamins A, C, D, E), and selenium.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOMEGA 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOMEGA 6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMUFA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePUFA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAnti-Oxidants\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ecarotenoids\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSelenium\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrelation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.065\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.173\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.019 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.378\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.363\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.022 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.024 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.039 *\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVitamin B6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVitamin B9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVitamin B12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVitamin E\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVitamin D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eVitamin C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eVitamin A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrelation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.071\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.071\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.159\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.479\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.318\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eB-Carotene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLycopene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLutein \u0026amp; zeaxanthin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ealpha-Carotene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ebeta-cryptoxanthin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrelation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.035 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.048 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.045 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e.457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnalysis of multivariate regression to predict disease progression by micronutrients after adjusting dietary variables for calorie intake. *P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ebeta coefficient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMUFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.186\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePUFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.867\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin E\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.577\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.530\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.496\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.501\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.507\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB-Carotene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOMEGA 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.038 *\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOMEGA 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.166\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ealpha-Carotene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.905\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.182\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ebeta-Cryptoxanthin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.261\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLycopene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLuteinzeaxanthin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study investigated the relationship between individual dietary components and cognitive decline in elderly patients with MCI and AD. The findings revealed several important associations between micronutrient intake and the progression and severity of the disease. Omega-3 fatty acids, carotenoids, and antioxidants, including vitamins A, C, D, E, and selenium, were found to be negatively correlated with disease severity. Moreover, selenium, alpha-carotene, beta-carotene, and lycopene levels declined in the more advanced stages of Alzheimer's disease. Interestingly, after adjusting for energy intake, only omega-3 fatty acid intake significantly predicted the progression of the disease.\u003c/p\u003e \u003cp\u003eThese findings are consistent with previous research that has investigated the impact of nutrition on cognitive function and Alzheimer's disease. Recent animal studies have shown that lycopene has protective properties by reducing oxidative stress, suppressing the production of inflammatory cytokines, and preventing the accumulation of amyloid plaques [\u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In addition, according to animal experiments, selenium-containing compounds influence the metabolism of neurotransmitters. However, the most important involvement of selenium in AD is the antioxidant function of various selenium-dependent enzymes[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Several studies have shown that Omega-3 fatty acids are associated with improved memory and reduced risk of Alzheimer's disease in the elderly [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Recently, beta-carotene has been shown to have a protective effect against oxidative stress and reduce AD risk .one study evaluated the effects of a beta-carotene-rich diet versus supplements on the risk of developing AD and found that it could significantly reduce its risk [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Several studies have shown that the carotene in fruits and vegetables can protect brain tissue from free radical damage, thereby improving cognitive function and memory [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Fat-soluble vitamins A, D, and E are considered antioxidants with potential benefits. In some studies, the serum levels of these vitamins were reduced in AD patients compared to healthy individuals [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, conflicting findings have been reported when examining the association between cognitive function or dementia and the consumption of certain antioxidants in fruits and vegetables, including beta-carotene, vitamins C and E, and flavonoids [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ethe results suggest that micronutrients, specifically omega-3 fatty acids, carotenoids, antioxidants, selenium, alpha-carotene, beta-carotene, and lycopene, play a crucial role in the progression and severity of AD in elderly individuals with mild cognitive impairment and AD. The negative correlations observed between these dietary factors and disease severity indicate that lower levels of these micronutrients are associated with more advanced stages of AD.\u003c/p\u003e \u003cp\u003eThe mechanism behind these associations can be attributed to the beneficial effects of these nutrients on brain health. Omega-3 fatty acids, particularly DHA, have positive effects on the regulation of inflammatory processes. They influence the inflammatory response by altering the structure and properties of cell membranes through their direct impact on receptor function and the activity of ion channels involved in immune activation. Recent research has indicated that a lack of production of anti-inflammatory substances plays a significant role in cognitive decline among patients with AD. Additionally, findings from epidemiological studies suggest the presence of a crucial period of at least two years prior to dementia onset in which there is an increase in proinflammatory substances in the brain, potentially influencing the progression of AD [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In light of these findings, researchers, propose that omega-3 supplementation may have preventive or disease-slowing benefits, but it may not be effective in treating dementia once it has already developed [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough the relationship between the characteristic lesions of AD pathology, such as B-amyloid and tau proteins, and oxidative stress is still not fully understood, there is a growing body of evidence suggesting that oxidative stress and the generation of free radicals play a role in the progression of cellular injury and death, which contributes to the development of neurodegenerative diseases [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Therefore, therapeutic interventions aimed at inhibiting oxidative stress, such as the use of antioxidant nutrients, may be beneficial in interrupting the cycle of cell death. In AD, oxidative stress is not only elevated but also persistent, and it occurs within an environment that becomes more susceptible to damage as a person ages. In addition to its involvement in AD pathology, oxidative stress has also been identified as a critical component in various steps of atherosclerosis and acute thrombotic events. These include dyslipidemia, the formation of atheroma, the oxidation of low-density lipoproteins, endothelial damage, plaque rupture, myocardial ischemic injury, and recurrent thrombosis. These pathways may be associated with the development and progression of vascular cognitive impairment and dementia. Therefore, the intake of dietary antioxidants can reduce the progress of cognitive decline in Alzheimer's by reducing oxidative stress [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The decline in these micronutrients in more advanced stages of AD may be due to various factors. Neuroinflammation and increased metabolic demands in AD can lead to increased oxidative stress and nutrient depletion. Additionally, changes in appetite, dietary patterns, and nutrient absorption associated with cognitive impairment may contribute to inadequate intake of these essential micronutrients.\u003c/p\u003e \u003cp\u003eThe study's strengths lie in its rigorous methodology, including a well-defined participant selection process, the use of validated assessment tools for dementia diagnosis and severity, and a comprehensive dish-based food frequency questionnaire for dietary assessment. Additionally, the study adjusted for potential confounding factors and applied appropriate statistical analyses to evaluate the correlations. However, some limitations should be acknowledged, such as the cross-sectional design, which limits causal inference, and the reliance on self-reported dietary data, which may be subject to recall bias, and the study was conducted in a specific population in Iran, which may limit the generalizability of the findings to other populations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCertain micronutrients, specifically omega-3 fatty acids, carotenoids, and antioxidants, may play a role in disease progression. Higher intake of omega-3 fatty acids was associated with slower disease progression in AD patients. Furthermore, the levels of these micronutrients declined in the more advanced stages of the disease, indicating their potential involvement in the pathogenesis and progression of AD. These results highlight the importance of considering individual dietary components and incorporating micronutrients into the diet of elderly individuals with cognitive impairment and AD. However, it is important to note that this study was cross-sectional in nature, and further longitudinal studies are needed to establish a causal relationship and determine the optimal intake of these micronutrients for disease management and prevention.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZV and RH contributed in conception, design, statistical analyses, data interpretation and manuscript drafting. CA, AR, HH, and MA contributed in data collection, interpretation and manuscript drafting. FE, DF and HR contributed to the data analysis and approving the final manuscript. ZV supervised the study. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo financial support was provided in any way for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available, but are available from the corresponding author at reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of the Tehran University of Medical Sciences approved the study (IR.TUMS.MEDICINE.REC.1400.893).\u0026nbsp;The legal guardians of the individuals signed an informed written consent.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Geriatric Medicine, Ziaeian Hospital, Tehran University of Medical Sciences, Tehran, Iran\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003eDepartment of Nutrition Research, \u0026nbsp;National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e4\u003c/sup\u003eDepartment of Nutrition Research, \u0026nbsp;National Nutrition and Food Technology Research Institute and Faculty of \u0026nbsp;Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e5\u003c/sup\u003eFaculty of Medicine, Tehran University of Medical Science, Tehran, Iran\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e6\u003c/sup\u003eDepartment of Psychiatry, Psychosomatic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e7\u003c/sup\u003eDepartment of Emergency Medicine, faculty of medicine, Tehran University of medical sciences, Tehran, Iran\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e8\u003c/sup\u003eFaculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e9\u003c/sup\u003eDepartment of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e10\u003c/sup\u003e Cognitive Neurology and Neuropsychiatry Division, Psychiatry Department, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e11\u003c/sup\u003eGeriatric Department, Ziaeeian Hospital, Tehran University of Medical Sciences, Tehran, Iran.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMangialasche F, Polidori MC, Monastero R, Ercolani S, Camarda C, Cecchetti R, et al. 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Food chemistry. 2018;238:134-8.\u003c/li\u003e\n\u003cli\u003eCharlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. Journal of chronic diseases. 1987;40 5:373-83.\u003c/li\u003e\n\u003cli\u003eGodin G, Shephard R. A simple method to assess exercise behavior in the community. Can J Appl Sport Sci. 1985;10 3:141-6.\u003c/li\u003e\n\u003cli\u003eCohen J. Statistical power analysis for the behavioral sciences New York. NY: Academic. 1988:54.\u003c/li\u003e\n\u003cli\u003eChen D, Huang C, Chen Z. A review for the pharmacological effect of lycopene in central nervous system disorders. Biomedicine \u0026amp; Pharmacotherapy. 2019;111:791-801.\u003c/li\u003e\n\u003cli\u003eLiu C-B, Wang R, Yi Y-F, Gao Z, Chen Y-Z. Lycopene mitigates \u0026beta;-amyloid induced inflammatory response and inhibits NF-\u0026kappa;B signaling at the choroid plexus in early stages of Alzheimer\u0026rsquo;s disease rats. 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International journal of molecular sciences. 2020;21 4:1505.\u003c/li\u003e\n\u003cli\u003eAraya-Quintanilla F, Guti\u0026eacute;rrez-Espinoza H, S\u0026aacute;nchez-Montoya U, Mu\u0026ntilde;oz-Ya\u0026ntilde;ez MJ, Baeza-Vergara A, Petersen-Yanjar\u0026iacute; M, et al. Effectiveness of omega-3 fatty acid supplementation in patients with Alzheimer disease: A systematic review and meta-analysis. Neurolog\u0026iacute;a (English Edition). 2020;35 2:105-14.\u003c/li\u003e\n\u003cli\u003eFreund-Levi Y, Eriksdotter-J\u0026ouml;nhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, et al. \u0026omega;-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Archives of neurology. 2006;63 10:1402-8.\u003c/li\u003e\n\u003cli\u003eAndersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nature medicine. 2004;10 Suppl 7:S18-S25.\u003c/li\u003e\n\u003cli\u003eCastellani RJ, Lee H-g, Perry G, Smith MA. Antioxidant protection and neurodegenerative disease: The role of amyloid-\u0026beta; and tau. American Journal of Alzheimer\u0026apos;s Disease \u0026amp; Other Dementias\u0026reg;. 2006;21 2:126-30.\u003c/li\u003e\n\u003cli\u003eRafnsson SB, Dilis V, Trichopoulou A. Antioxidant nutrients and age-related cognitive decline: a systematic review of population-based cohort studies. European Journal of Nutrition. 2013;52 6:1553-67; doi: 10.1007/s00394-013-0541-7.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Alzheimer's disease, dementia, micronutrients, omega-3, carotenoids, antioxidants","lastPublishedDoi":"10.21203/rs.3.rs-4231202/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4231202/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are significant neurodegenerative disorders with increasing prevalence worldwide. Lifestyle and dietary factors, including micronutrients, have been suggested as modifiable risk factors for disease development. This study aims to investigate the association between micronutrients and cognitive ability in these diseases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A cross-sectional, randomized controlled study was conducted, involving 105 participants with MCI and AD. Dietary assessments were performed using a validated food frequency questionnaire, and micronutrient intake was calculated based on nutrient content. Disease severity was evaluated using the Functional Assessment Staging Tool (FAST). Statistical analyses, including correlation coefficients and multiple regression models, were employed to examine the association between micronutrients and disease progression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The results revealed significant correlations between disease severity and several micronutrients, including omega-3 fatty acids (B = -0.2, P = 0.01), carotenoids (B = -0.19, P = 0.02), antioxidants (B = -0.19, P = 0.02), selenium (B = -0.17, P = 0.03), alpha-carotene (B = -0.16, P = 0.04), beta-carotene (B = -0.17, P = 0.03), and lycopene (B = -0.16, P = 0.04). Multivariate regression analysis showed that higher intake of omega-3 fatty acids was associated with slower disease progression. Furthermore, the levels of these micronutrients declined in advanced stages of the disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Omega-3 fatty acids, carotenoids, and antioxidants may affect the cognitive ability and disease progression. Further longitudinal studies are warranted to establish causality and explore the therapeutic implications of these findings for the prevention and management of MCI and AD.\u003c/p\u003e","manuscriptTitle":"The relationship between micronutrients and cognitive ability in an elderly population with mild cognitive impairment and Alzheimer's disease: a cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-07 18:40:13","doi":"10.21203/rs.3.rs-4231202/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-30T19:57:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-26T14:19:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"244320689594243501776840425271516397057","date":"2024-07-26T09:59:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"29453535190450821010114040664403841382","date":"2024-07-22T06:48:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289954271038929928962212913514503965968","date":"2024-07-22T06:14:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-21T14:25:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"317772101006917035714332726140410896695","date":"2024-07-20T14:22:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-20T09:12:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-04-30T14:31:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-29T06:34:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-29T06:34:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2024-04-07T11:53:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5892f1a6-c346-444f-a785-9f1137469f16","owner":[],"postedDate":"May 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-28T16:08:20+00:00","versionOfRecord":{"articleIdentity":"rs-4231202","link":"https://doi.org/10.1186/s12883-024-03800-2","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2024-10-25 15:57:44","publishedOnDateReadable":"October 25th, 2024"},"versionCreatedAt":"2024-05-07 18:40:13","video":"","vorDoi":"10.1186/s12883-024-03800-2","vorDoiUrl":"https://doi.org/10.1186/s12883-024-03800-2","workflowStages":[]},"version":"v1","identity":"rs-4231202","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4231202","identity":"rs-4231202","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}