Serum iron parameters, HFE C282Y genotype, and cognitive performance in older adults: Results from the FACIT study

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volumn 65 A, Issue 12, 2010, Pages 1312-1321

  Schiepers, Olga J G ^a   Van Boxtel, Martin P J ^a   De Groot, Renate H M ^a,b,c   Jolles, Jelle ^a,b   De Kort, Wim L A M ^d   Swinkels, Dorine W ^e   Kok, Frans J ^f   Verhoef, Petra ^f,g,h   Durga, Jane ^f,g,i  

^a MAASTRICHT UNIVERSITY   (Netherlands)

^b VU UNIVERSITY AMSTERDAM   (Netherlands)

^c OPEN UNIVERSITY OF THE NETHERLANDS   (Netherlands)

^d Sanquin Blood Bank South East Region ^*  (Netherlands)

^e RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^f WAGENINGEN UNIVERSITY   (Netherlands)

^g TOP INSTITUTE FOOD AND NUTRITION   (Netherlands)

^h UNILEVER RESEARCH VLAARDINGEN   (Netherlands)

ⁱ NESTLÉ RESEARCH CENTER   (Switzerland)

Author keywords

Cognitive performance; HFE; Iron parameters; Longitudinal study; Older adults

Indexed keywords

ANTIANEMIC AGENT; CYSTEINE; FERRITIN; FOLIC ACID; IRON; TYROSINE;

AGED; ARTICLE; BLOOD; CLINICAL TRIAL; COGNITION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFECT; FEMALE; FOLLOW UP; GENETICS; GENOTYPE; HEMOCHROMATOSIS; HUMAN; INTIMA; MALE; MIDDLE AGED; MUTATION; PATHOLOGY; RANDOMIZED CONTROLLED TRIAL; TUNICA MEDIA;

AGED; COGNITION; CROSS-SECTIONAL STUDIES; CYSTEINE; DOUBLE-BLIND METHOD; FEMALE; FERRITINS; FOLIC ACID; FOLLOW-UP STUDIES; GENOTYPE; HEMATINICS; HEMOCHROMATOSIS; HUMANS; IRON; MALE; MIDDLE AGED; MUTATION; TUNICA INTIMA; TUNICA MEDIA; TYROSINE;

EID: 78649542630     PISSN: 10795006     EISSN: 1758535X     Source Type: Journal    
DOI: 10.1093/gerona/glq149     Document Type: Article

References (68)

1. Carter CS, Leeuwenburgh C, Daniels M, Foster TC. Infuence of calorie restriction on measures of age-related cognitive decline: role of increased physical activity. J Gerontol A Biol Sci Med Sci. 2009;64(8): 850-859.
2. Petursdottir AL, Farr SA, Morley JE, Banks WA, Skuladottir GV. Effect of dietary n-3 polyunsaturated fatty acids on brain lipid fatty acid composition, learning ability, and memory of senescence-accelerated mouse. J Gerontol A Biol Sci Med Sci. 2008;63(11):1153-1160.
3. Stephan BC, Wells JC, Brayne C, Albanese E, Siervo M. Increased fructose intake as a risk factor for dementia. J Gerontol A Biol Sci Med Sci. 2010;65(8):809-814.
4. Youdim MB. Brain iron defciency and excess; cognitive impairment and neurodegeneration with involvement of striatum and hippocampus. Neurotox Res. 2008;14(1):45-56.
5. Brussaard JH, Brants HA, Bouman M, Lowik MR. Iron intake and iron status among adults in the Netherlands. Eur J Clin Nutr. 1997; 51(suppl 3):S51-S58.
6. Ahmed F, Coyne T, Dobson A, McClintock C. Iron status among Australian adults: fndings of a population based study in Queensland, Australia. Asia Pac J Clin Nutr. 2008;17(1):40-47.
7. Lahti-Koski M, Valsta LM, Alfthan G, Tapanainen H, Aro A. Iron status of adults in the capital area of Finland. Eur J Nutr. 2003;42(5):287-292.
8. Milman N, Byg KE, Ovesen L. Iron status in Danes 1994. II: prevalence of iron defciency and iron overload in 1319 Danish women aged 40-70 years. Infuence of blood donation, alcohol intake and iron supplementation. Ann Hematol. 2000;79(11):612-621.
9. Killip S, Bennett JM, Chambers MD. Iron defciency anemia. Am Fam Physician. 2007;75(5):671-678.
10. Sandstead HH. Causes of iron and zinc defciencies and their effects on brain. J Nutr. 2000;130(2S suppl):347S-349S.
11. Murray RK, Granner DK, Mayes PA, Rodwell VW. Harper's Biochemistry, 24th ed. Stamford, CT: Appleton & Lange; 1996.
12. Thompson KJ, Shoham S, Connor JR. Iron and neurodegenerative disorders. Brain Res Bull. 2001;55(2):155-164.
13. Beard JL, Connor JR. Iron status and neural functioning. Annu Rev Nutr. 2003;23:41-58.
14. Hidalgo C, Núñez MT. Calcium, iron and neuronal function. IUBMB Life. 2007;59(4-5):280-285.
15. Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr. 2007;85(3):778-787.
16. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW. Poorer behavioral and developmental outcome more than 10 years after treatment for iron defciency in infancy. Pediatrics. 2000;105(4):E51.
17. McCann JC, Ames BN. An overview of evidence for a causal relation between iron defciency during development and defcits in cognitive or behavioral function. Am J Clin Nutr. 2007;85(4):931-945.
18. Halterman JS, Kaczorowski JM, Aligne CA, Auinger P, Szilagyi PG Iron defciency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics. 2001;107(6): 1381-1386.
19. Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-defcient adolescent girls. Lancet. 1996;348(9033):992-996.
20. Gao S, Jin Y, Unverzagt FW, et al. Trace element levels and cognitive function in rural elderly Chinese. J Gerontol A Biol Sci Med Sci. 2008;63(6):635-641.
21. La Rue A, Koehler KM, Wayne SJ, Chiulli SJ, Haaland KY, Garry PJ. Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment. Am J Clin Nutr. 1997;65(1):20-29.
22. Lam PK, Kritz-Silverstein D, Barrett Connor E, et al. Plasma trace elements and cognitive function in older men and women: the Rancho Bernardo study. J Nutr Health Aging. 2008;12(1):22-27.
23. Handelman GJ, Levin NW. Iron and anemia in human biology: a review of mechanisms. Heart Fail Rev. 2008;13(4):393-404.
24. Weiss G. Iron metabolism in the anemia of chronic disease. Biochim Biophys Acta. 2009;1790(7):682-693.
25. Marshall TA, Stumbo PJ, Warren JJ, Xie XJ. Inadequate nutrient intakes are common and are associated with low diet variety in rural, community-dwelling elderly. J Nutr. 2001;131(8):2192-2196.
26. Koziol JA, Ho NJ, Felitti VJ, Beutler E. Reference centiles for serum ferritin and percentage of transferrin saturation, with application to mutations of the HFE gene. Clin Chem. 2001;47(10):1804-1810.
27. Fleming DJ, Jacques PF, Tucker KL, et al. Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores. Am J Clin Nutr. 2001;73(3):638-646.
28. Njajou OT, Houwing-Duistermaat JJ, Osborne RH, et al. A population-based study of the effect of the HFE C282Y and H63D mutations on iron metabolism. Eur J Hum Genet. 2003;11(3):225-231.
29. Wrede CE, Hutzler S, Bollheimer LC, et al. Correlation between iron status and genetic hemochromatosis (codon C282Y) in a large German population. Isr Med Assoc J. 2004;6(1):30-33.
30. Schmechel DE, Browndyke J, Ghio A. Strategies for dissecting genetic-environmental interactions in neurodegenerative disorders. Neurotoxicology. 2006;27(5):637-657.
31. Guerreiro RJ, Bras JM, Santana I, et al. Association of HFE common mutations with Parkinson's disease, Alzheimer's disease and mild cognitive impairment in a Portuguese cohort. BMC Neurol. 2006;6:24.
32. Lehmann DJ, Worwood M, Ellis R, et al. Iron genes, iron load and risk of Alzheimer's disease. J Med Genet. 2006;43(10):e52.
33. Robson KJ, Lehmann DJ, Wimhurst VL, et al. Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer's disease. J Med Genet. 2004;41(4):261-265.
34. Berlin D, Chong G, Chertkow H, Bergman H, Phillips NA, Schipper HM. Evaluation of HFE (hemochromatosis) mutations as genetic modifers in sporadic AD and MCI. Neurobiol Aging. 2004;25(4):465-474.
35. Biasiotto G, Goldwurm S, Finazzi D, et al. HFE gene mutations in a population of Italian Parkinson's disease patients. Parkinsonism Relat Disord. 2008;14(5):426-430.
36. Correia AP, Pinto JP, Dias V, Mascarenhas C, Almeida S, Porto G CAT53 and HFE alleles in Alzheimer's disease: a putative protective role of the C282Y HFE mutation. Neurosci Lett. 2009;457(3): 129-132.
37. Durga J, Van Boxtel MPJ, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007;369(9557): 208-216.
38. Van der Elst W, Van Boxtel MPJ, Van Breukelen GJP, Jolles J. Rey's verbal learning test: normative data for 1855 healthy participants aged 24-81 years and the infuence of age, sex, education, and mode of presentation. J Int Neuropsychol Soc. 2005;11(3):290-302.
39. Van der Elst W, Van Boxtel MPJ, Van Breukelen GJP, Jolles J. The Stroop color-word test: infuence of age, sex, and education; and normative data for a large sample across the adult age range. Assessment. 2006;13(1):62-79.
40. Van der Elst W, Van Boxtel MPJ, Van Breukelen GJP, Jolles J. The Concept Shifting Test: adult normative data. Psychol Assess. 2006;18(4):424-432.
41. Van der Elst W, Van Boxtel MPJ, Van Breukelen GJP, Jolles J. The Letter Digit Substitution Test: normative data for 1,858 healthy participants aged 24-81 from the Maastricht Aging Study (MAAS): infuence of age, education, and sex. J Clin Exp Neuropsychol. 2006;28(6): 998-1009.
42. Van der Elst W, Van Boxtel MPJ, Van Breukelen GJP, Jolles J. Normative data for the Animal, Profession and Letter M Naming verbal fuency tests for Dutch speaking participants and the effects of age, education, and sex. J Int Neuropsychol Soc. 2006;12(1):80-90.
43. Gambino R, Desvarieux E, Orth M, et al. The relation between chemically measured total iron-binding capacity concentrations and immunologically measured transferrin concentrations in human serum. Clin Chem. 1997;43(12):2408-2412.
44. Vernet M, Le Gall JY. Transferrin saturation and screening of genetic hemochromatosis. Clin Chem. 1998;44(2):360-362.
45. Cook JD, Lipschitz DA, Mies LE, Finch CA. Serum ferritin as a measure of iron stores in normal subjects. Am J Clin Nutr. 1974;27(7):681-687.
46. Hider RC. Nature of nontransferrin-bound iron. Eur J Clin Invest. 2002;32(suppl 1):50-54.
47. Breuer W, Hershko C, Cabantchik ZI. The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus Sci. 2000; 23(3):185-192.
48. Breuer W, Cabantchik ZI. A fuorescence-based one-step assay for serum non-transferrin-bound iron. Anal Biochem. 2001;299(2):194-202.
49. De Kok JB, Wiegerinck ET, Giesendorf BA, Swinkels DW. Rapid genotyping of single nucleotide polymorphisms using novel minor groove binding DNA oligonucleotides (MGB probes). Hum Mutat. 2002;19(5):554-559.
50. Jeffrey GP, Chakrabarti S, Hegele RA, Adams PC. Polymorphism in intron 4 of HFE may cause overestimation of C282Y homozygote prevalence in haemochromatosis. Nat Genet. 1999;22(4):325-326.
51. Lynas C. A cheaper and more rapid polymerase chain reaction-restriction fragment length polymorphism method for the detection of the HLA-H gene mutations occurring in hereditary hemochromatosis. Blood. 1997;90(10):4235-4236.
52. De Bie SE. Standaardvragen 1987: Voorstellen voor uniformering van vraagstellingen naar achtergrondkenmerken en interviews (Dutch) [Standard Questions 1987: Proposal for Uniformization of Questions Regarding Background Variables and Interviews]. 2nd ed. Leiden, The Netherlands: Leiden University Press; 1987.
53. Washburn RA, Smith KW, Jette AM, Janney CA. The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol. 1993;46(2):153-162.
54. Cunietti E, Chiari MM, Monti M, et al. Distortion of iron status indices by acute infammation in older hospitalized patients. Arch Gerontol Geriatr. 2004;39(1):35-42.
55. Pulliam JF, Jennings CD, Kryscio RJ, et al. Association of HFE mutations with neurodegeneration and oxidative stress in Alzheimer's disease and correlation with APOE. Am J Med Genet B Neuropsychiatr Genet. 2003;119B(1):48-53.
56. Shah RC, Wilson RS, Tang Y, Dong X, Murray A, Bennett DA. Relation of hemoglobin to level of cognitive function in older persons. Neuroepidemiology. 2009;32(1):40-46.
57. Mitsopoulos E, Zanos S, Ginikopoulou E, et al. Do serum and red blood cell folate levels indicate iron response in hemodialysis patients? ASAIO J. 2006;52(2):163-168.
58. Verbeke G, Molenberghs G. Linear Mixed Models for Longitudinal Data. New York: Springer; 2000.
59. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107(3):363-369.
60. Tobin MD, Minelli C, Burton PR, Thompson JR. Commentary: development of Mendelian randomization: from hypothesis test to 'Mende-lian deconfounding'. Int J Epidemiol. 2004;33(1):26-29.
61. Gómez-Llorente C, Miranda-León MT, Blanco S, Gandia-Pla S, Gómez-Capilla JA, Fárez-Vidal ME. Frequency and clinical expression of HFE gene mutations in a Spanish population of subjects with abnormal iron metabolism. Ann Hematol. 2005;84(10):650-655.
62. Kartikasari AE, Georgiou NA, Visseren FL, Van Kats-Renaud H, Van Asbeck BS, Marx JJ. Endothelial activation and induction of monocyte adhesion by nontransferrin-bound iron present in human sera. FASEB J. 2006;20(2):353-355.
63. De Valk B, Addicks MA, Gosriwatana I, Lu S, Hider RC, Marx JJ. Non-transferrin-bound iron is present in serum of hereditary haemochromatosis heterozygotes. Eur J Clin Invest. 2000;30(3):248-251.
64. Deary IJ, Whiteman MC, Pattie A, et al. Cognitive change and the APOE epsilon 4 allele. Nature. 2002;418(6901):932.
65. Smith JD. Apolipoproteins and aging: emerging mechanisms. Ageing Res Rev. 2002;1(3):345-365.
66. Dale JC, Burritt MF, Zinsmeister AR. Diurnal variation of serum iron, iron-binding capacity, transferrin saturation, and ferritin levels. Am J Clin Pathol. 2002;117(5):802-808.
67. Mizuno S, Mihara T, Miyaoka T, Inagaki T, Horiguchi J. CSF iron, ferritin and transferrin levels in restless legs syndrome. J Sleep Res. 2005;14(1):43-47.
68. Haba-Rubio J, Staner L, Petiau C, Erb G, Schunck T, Macher JP Restless legs syndrome and low brain iron levels in patients with haemochromatosis. J Neurol Neurosurg Psychiatry. 2005;76(7): 1009-1010.