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Serum zinc concentration and dietary zinc intake in relation to cognitive function: an analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort

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Abstract

Purpose

There are several pathways by which zinc may be a modifiable factor to slow age-related cognitive decline. We investigated the associations between serum and dietary zinc and cognitive impairment in a longitudinal cohort.

Methods

We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort (n = 30,239) and the REGARDS Trace Element Study (n = 2666). Baseline serum zinc concentrations (2003–2007) were measured using inductively coupled plasma mass spectrometry. Baseline dietary zinc intake was measured via the Block food frequency questionnaire. Serum zinc concentrations and dietary zinc intake were categorized into quartiles. The outcome of interest was impairment on the Six-Item Screener (SIS), a measure of global cognitive functioning administered annually. The Enhanced Cognitive Battery (ECB), a more comprehensive series of tests assessing memory and fluency, was administered every two years and considered a secondary outcome. Associations between zinc and incident impairment were assessed using multivariable logistic regression.

Results

Among 2065 participants with serum zinc data, 184 individuals developed impairment over 10 years of follow-up. In adjusted models, there was no significant association between serum zinc and impairment as assessed by the SIS or the ECB. Among 18,103 participants who had dietary data, 1424 experienced incident impairment on the SIS. Dietary zinc intake was not significantly associated with impairment as assessed by the SIS or the ECB in adjusted models.

Conclusion

Findings from this U.S. cohort did not support the hypothesis that serum zinc concentration or dietary zinc intake is associated with the risk of cognitive impairment.

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References

  1. Matthews KA, Xu W, Gaglioti AH, Holt JB, Croft JB, Mack D, McGuire LC (2019) Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥ 65 years. Alzheimers Dement 15(1):17–24. https://doi.org/10.1016/j.jalz.2018.06.3063

    Article  PubMed  Google Scholar 

  2. Tahami Monfared AA, Byrnes MJ, White LA, Zhang Q (2022) The Humanistic and economic burden of Alzheimer’s disease. Neurol Ther. https://doi.org/10.1007/s40120-022-00335-x

    Article  PubMed  PubMed Central  Google Scholar 

  3. Deb A, Thornton JD, Sambamoorthi U, Innes K (2017) Direct and indirect cost of managing Alzheimer’s disease and related dementias in the United States. Expert Rev Pharm Out 17(2):189–202. https://doi.org/10.1080/14737167.2017.1313118

    Article  Google Scholar 

  4. Xie ZY, Wu HR, Zhao JF (2020) Multifunctional roles of zinc in Alzheimer’s disease. Neurotoxicology 80:112–123. https://doi.org/10.1016/j.neuro.2020.07.003

    Article  CAS  PubMed  Google Scholar 

  5. Hancock SM, Finkelstein DI, Adlard PA (2014) Glia and zinc in ageing and Alzheimer’s disease: a mechanism for cognitive decline? Front Aging Neurosci. https://doi.org/10.3389/fnagi.2014.00137

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kim JW, Byun MS, Yi D, Lee JH, Kim MJ, Jung G, Lee JY, Kang KM, Sohn CH, Lee YS, Kim YK, Lee DY, Grp KR (2021) Serum zinc levels and in vivo beta-amyloid deposition in the human brain. Alzheimers Res Ther. https://doi.org/10.1186/s13195-021-00931-3

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ortega RM, Requejo AM, Andres P, Lopez-Sobaler AM, Quintas ME, Redondo MR, Navia B, Rivas T (1997) Dietary intake and cognitive function in a group of elderly people. Am J Clin Nutr 66(4):803–809. https://doi.org/10.1093/ajcn/66.4.803

    Article  CAS  PubMed  Google Scholar 

  8. Ventriglia M, Brewer GJ, Simonelli I, Mariani S, Siotto M, Bucossi S, Squitti R (2015) Zinc in Alzheimer’s disease: a meta-analysis of serum, plasma, and cerebrospinal fluid studies. J Alzheimers Dis 46(1):75–87. https://doi.org/10.3233/Jad-141296

    Article  CAS  PubMed  Google Scholar 

  9. Socha K, Klimiuk K, Naliwajko SK, Soroczynska J, Puscion-Jakubik A, Markiewicz-Zukowska R, Kochanowicz J (2021) Dietary habits, selenium, copper, zinc and total antioxidant status in serum in relation to cognitive functions of patients with Alzheimer’s disease. Nutrients 13(2):287. https://doi.org/10.3390/nu13020287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang ZX, Tan L, Wang HF, Ma J, Liu J, Tan MS, Sun JH, Zhu XC, Jiang T, Yu JT (2015) Serum iron, zinc, and copper levels in patients with Alzheimer’s disease: a replication study and meta-analyses. J Alzheimers Dis 47(3):565–581. https://doi.org/10.3233/JAD-143108

    Article  CAS  PubMed  Google Scholar 

  11. Shang N, Zhang L, Wang S, Huang T, Wang YH, Gao XC, Xu SM, Zhang JQ, Zhang L, Niu Q, Zhang QL (2021) Increased aluminum and lithium and decreased zinc levels in plasma is related to cognitive impairment in workers at an aluminum factory in China: a cross-sectional study. Ecotox Environ Safe. https://doi.org/10.1016/j.ecoenv.2021.112110

    Article  Google Scholar 

  12. Markiewicz-Zukowska R, Gutowska A, Borawska MH (2015) Serum Zinc Concentrations Correlate with Mental and Physical Status of Nursing Home Residents. PLoS ONE 10(1):e0117257. https://doi.org/10.1371/journal.pone.0117257

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mravunac M, Szymlek-Gay EA, Daly RM, Roberts BR, Formica M, Gianoudis J, O’Connell SL, Nowson CA, Cardoso BR (2019) Greater circulating copper concentrations and copper/zinc ratios are associated with lower psychological distress, but not cognitive performance, in a sample of Australian older adults. Nutrients 11(10):2503. https://doi.org/10.3390/nu11102503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rembach A, Hare DJ, Doecke JD, Burnham SC, Volitakis I, Fowler CJ, Cherny RA, McLean C, Grimm R, Martins R, Ames D, Masters CL, Bush AI, Roberts BR (2014) Decreased serum zinc is an effect of ageing and not Alzheimer’s disease. Metallomics 6(7):1216–1219. https://doi.org/10.1039/c4mt00060a

    Article  CAS  PubMed  Google Scholar 

  15. Klinedinst BS, Le ST, Larsen B, Pappas C, Hoth NJ, Pollpeter A, Wang Q, Wang YY, Yu S, Wang L, Allenspach K, Mochel JP, Bennett DA, Willette AA (2020) Genetic factors of Alzheimer’s disease modulate how diet is associated with long-term cognitive trajectories: a UK biobank study. J Alzheimers Dis 78(3):1245–1257. https://doi.org/10.3233/Jad-201058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cherian L, Wang Y, Fakuda K, Leurgans S, Aggarwal N, Morris M (2019) Mediterranean-dash intervention for neurodegenerative delay (MIND) diet slows cognitive decline after stroke. J Prev Alzheimers Dis 6(4):267–273. https://doi.org/10.14283/jpad.2019.28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Howard VJ, Cushman M, Pulley L, Gomez CR, Go RC, Prineas RJ, Graham A, Moy CS, Howard G (2005) The reasons for geographic and racial differences in stroke study: objectives and design. Neuroepidemiology 25(3):135–143. https://doi.org/10.1159/000086678

    Article  PubMed  Google Scholar 

  18. Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L (1986) A data-based approach to diet questionnaire design and testing. Am J Epidemiol 124(3):453–469. https://doi.org/10.1093/oxfordjournals.aje.a114416

    Article  CAS  PubMed  Google Scholar 

  19. Newby PK, Noel SE, Grant R, Judd S, Shikany JM, Ard J (2012) Race and region have independent and synergistic effects on dietary intakes in black and white women. Nutr J 11:25. https://doi.org/10.1186/1475-2891-11-25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Judd SE, Letter AJ, Shikany JM, Roth DL, Newby PK (2014) Dietary patterns derived using exploratory and confirmatory factor analysis are stable and generalizable across race, region, and gender subgroups in the REGARDS study. Front Nutr 1:29. https://doi.org/10.3389/fnut.2014.00029

    Article  PubMed  Google Scholar 

  21. Shikany JM, Safford MM, Newby PK, Durant RW, Brown TM, Judd SE (2015) Southern dietary pattern is associated with hazard of acute coronary heart disease in the reasons for geographic and racial differences in stroke (REGARDS) study. Circulation 132(9):804–814. https://doi.org/10.1161/CIRCULATIONAHA.114.014421

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gillett SR, Boyle RH, Zakai NA, McClure LA, Jenny NS, Cushman M (2014) Validating laboratory results in a national observational cohort study without field centers: the reasons for geographic and racial differences in stroke cohort. Clin Biochem 47(16–17):243–246. https://doi.org/10.1016/j.clinbiochem.2014.08.003

    Article  PubMed  PubMed Central  Google Scholar 

  23. Callahan CM, Unverzagt FW, Hui SL, Perkins AJ, Hendrie HC (2002) Six-item screener to identify cognitive impairment among potential subjects for clinical research. Med Care 40(9):771–781. https://doi.org/10.1097/00005650-200209000-00007

    Article  PubMed  Google Scholar 

  24. Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C (1989) The consortium to establish a registry for Alzheimer’s disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology 39(9):1159–1165. https://doi.org/10.1212/wnl.39.9.1159

    Article  CAS  PubMed  Google Scholar 

  25. Rosen WG (1980) Verbal fluency in aging and dementia. J Clin Neuropsychol 2(2):135–146. https://doi.org/10.1080/01688638008403788

    Article  Google Scholar 

  26. Unverzagt FW, McClure LA, Wadley VG, Jenny NS, Go RC, Cushman M, Kissela BM, Kelley BJ, Kennedy R, Moy CS, Howard V, Howard G (2011) Vascular risk factors and cognitive impairment in a stroke-free cohort. Neurology 77(19):1729–1736. https://doi.org/10.1212/WNL.0b013e318236ef23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kohout FJ, Berkman LF, Evans DA, Cornoni-Huntley J (1993) Two shorter forms of the CES-D (Center for epidemiological studies depression) depression symptoms index. J Aging Health 5(2):179–193. https://doi.org/10.1177/089826439300500202

    Article  CAS  PubMed  Google Scholar 

  28. Brzoska MM, Moniuszko-Jakoniuk J (2001) Interactions between cadmium and zinc in the organism. Food Chem Toxicol 39(10):967–980. https://doi.org/10.1016/S0278-6915(01)00048-5

    Article  CAS  PubMed  Google Scholar 

  29. (2001) In: Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington (DC). https://doi.org/10.17226/10026

  30. Li DD, Zhang W, Wang ZY, Zhao P (2017) Serum copper, zinc, and iron levels in patients with Alzheimer’s disease: a meta-analysis of case-control studies. Front Aging Neurosci 9:300. https://doi.org/10.3389/fnagi.2017.00300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li S, Sun W, Zhang D (2019) Association of zinc, iron, copper, and selenium intakes with low cognitive performance in older adults: a cross-sectional study from national health and nutrition examination survey (NHANES). J Alzheimers Dis 72(4):1145–1157. https://doi.org/10.3233/JAD-190263

    Article  PubMed  Google Scholar 

  32. Wang X, Wang H, Zhang F, Cui Y, Zhang D, Shen X (2022) Threshold effects and interactive effects of total zinc and selenium intake on cognitive function in older adults. Clin Nutr ESPEN 47:383–390. https://doi.org/10.1016/j.clnesp.2021.11.001

    Article  PubMed  Google Scholar 

  33. Maylor EA, Simpson EE, Secker DL, Meunier N, Andriollo-Sanchez M, Polito A, Stewart-Knox B, McConville C, O’Connor JM, Coudray C (2006) Effects of zinc supplementation on cognitive function in healthy middle-aged and older adults: the ZENITH study. Br J Nutr 96(4):752–760

    CAS  PubMed  Google Scholar 

  34. Yaffe K, Clemons TE, McBee WL, Lindblad AS, Age-Related Eye Disease Study Research G (2004) Impact of antioxidants, zinc, and copper on cognition in the elderly: a randomized, controlled trial. Neurology 63(9):1705–1707. https://doi.org/10.1212/01.wnl.0000142969.19465.8f

    Article  CAS  PubMed  Google Scholar 

  35. Kesse-Guyot E, Fezeu L, Jeandel C, Ferry M, Andreeva V, Amieva H, Hercberg S, Galan P (2011) French adults’ cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the supplementation in vitamins and mineral antioxidants (SU.VI.MAX) trial. Am J Clin Nutr 94(3):892–899. https://doi.org/10.3945/ajcn.110.007815

    Article  CAS  PubMed  Google Scholar 

  36. King JC, Brown KH, Gibson RS, Krebs NF, Lowe NM, Siekmann JH, Raiten DJ (2015) Biomarkers of nutrition for development (BOND)-zinc review. J Nutr 146(4):858S-885S. https://doi.org/10.3945/jn.115.220079

    Article  PubMed  Google Scholar 

  37. Hennigar SR, Lieberman HR, Fulgoni VL 3rd, McClung JP (2018) Serum Zinc concentrations in the US population are related to sex, age, and time of blood draw but not dietary or supplemental zinc. J Nutr 148(8):1341–1351. https://doi.org/10.1093/jn/nxy105

    Article  PubMed  Google Scholar 

  38. Boucher B, Cotterchio M, Kreiger N, Nadalin V, Block T, Block G (2006) Validity and reliability of the Block98 food-frequency questionnaire in a sample of Canadian women. Public Health Nutr 9(1):84–93. https://doi.org/10.1079/phn2005763

    Article  PubMed  Google Scholar 

  39. Tran J, Nimojan T, Saripella A, Tang-Wai DF, Butris N, Kapoor P, Berezin L, Englesakis M, Chung F (2022) Rapid cognitive assessment tools for screening of mild cognitive impairment in the preoperative setting: a systematic review and meta-analysis. J Clin Anesth 78:110682. https://doi.org/10.1016/j.jclinane.2022.110682

    Article  PubMed  Google Scholar 

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Funding

The REGARDS Trace Element Study is supported by a research grant from the National Institutes of Health (NIH) (RF1AG056111). REGARDS is supported by cooperative agreement U01 NS041588 co-funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Service. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIA. Representatives of the NINDS were involved in the review of the manuscript but were not directly involved in the collection, management, analysis, or interpretation of the data. The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at https://www.uab.edu/soph/regardsstudy/.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, 622 W 168th Street, Room 16–20, New York, NY, 10032, USA

    Meghan Angley, Yijia Zhang, Liping Lu, Shai Bejerano & Ka Kahe

  2. Department of Epidemiology, Columbia University Irving Medical Center, New York, NY, USA

    Meghan Angley, Yijia Zhang, Liping Lu & Ka Kahe

  3. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

    Frederick Unverzagt

  4. Department of Chemistry, University of Missouri Research Reactor, University of Missouri, Columbia, MI, USA

    John Brockman

  5. Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA

    Leslie A. McClure

  6. Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA

    Suzanne Judd

  7. Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA

    Mary Cushman

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  1. Meghan Angley
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Correspondence to Ka Kahe.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Written informed consent was obtained from all participants. This study was approved by the Institutional Review Boards (IRB) of all participating REGARDS institutions and the IRB of Columbia University Irving Medical Center (IRB AAAS9507).

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Angley, M., Zhang, Y., Lu, L. et al. Serum zinc concentration and dietary zinc intake in relation to cognitive function: an analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Eur J Nutr (2024). https://doi.org/10.1007/s00394-023-03294-7

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