Folate nutrition is related to neuropsychological functions in the elderly

  • Chang, Nam-Soo (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Eun-Jung (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Ki-Nam (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Hye-Sook (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Seong-Yoon (Department of Psychiatry, Asan Medical Center) ;
  • Jeong, Bum-Seok (Department of Psychiatry, Asan Medical Center)
  • Published : 2009.03.31

Abstract

We investigated the nutritional state of B vitamins and the neuropsychological functions in 25 subjects, aged $63.1{\pm}6.3$ years, residing in rural areas of Korea. Nutritional states of thiamin, riboflavin, and pyridoxine were assessed enzymatically in the erythrocytes, and folate concentrations were measured microbiologically in the plasma and erythrocytes. A battery of composite neuropsychological test was administered to the subjects. Plasma folate was correlated with the total intelligence score (p=0.049). Folate levels in the erythrocytes were correlated with the performance intelligence scores such as block design (p=0.017) and picture arrangement (p=0.016). The red cell folate was correlated with memory scores such as general memory (p=0.009) and delayed recall (p=0.000). Although it did not reach statistical significance, verbal memory (p=0.053) was highly correlated with the red cell folate. The red cell folate was also correlated positively with the percent of conceptual level response number score (p=0.029), and negatively with the grooved pegboard test score for the non-dominant hand (p=0.010). Fine motor coordination was also influenced by folate nutrition, as finger tapping scores in both hands were significantly correlated with red cell folate (dominant hand; p=0.026, non-dominant hand; p=0.004). Other B vitamins such as thiamin, riboflavin, and vitamin $B_6$ were not as strongly correlated with neuropsychological function test scores as folate was. These results suggest that folate nutrition influences neuropsychological function test scores significantly in humans. Further studies are needed to explore the relationship between folate or other vitamin B nutrition and neuropsychological functions and the implications thereof.

Keywords

References

  1. Albright CD, Tsai AY, Friedrich CB, Mar MH & Zeisel SH (1999). Choline availability alters embryonic development of the hippocampus and septum in the rat. Brain Res Dev Brain Res 113:13-20 https://doi.org/10.1016/S0165-3806(98)00183-7
  2. Baker H, De Angelis B, Baker ER, Frank O & Jaslowdagger SP (1999). Lack of effect of 1 year of a high-dose vitamin and mineral supplement on cognitive function of elderly women. Gerontology 45:195-199 https://doi.org/10.1159/000022086
  3. Baker SK & Tarnopolsky MA (2003). Targeting cellular energy production in neurological disorders. Expert Opin Investig Drugs 12:1655-1679 https://doi.org/10.1517/13543784.12.10.1655
  4. Balaghi M, Horne DW & Wagner C (1993). Hepatic one-carbon metabolism in early folate deficiency in rats. Biochem J 1:145-149
  5. Bayoumi RA & Rosalki SB (1976). Evalution of methods of coenzyme activation of erythrocyte enzymes for detection of deficiency of vitamins $B_{1}\;B_{2}$, and $B_{6}$. Clin Chem 22:327
  6. Bell IR, Edman JS, Marby DW, Satlin A, Dreir T, Piptzin B & Cole JO (1990). Vitamin B12 and folate status in acute geropsychiatric inpatients: affective and cognitive characteristics of vitamin nondeficient population. Biol Psychiatry 27:125
  7. Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, Wickramasinghe SN, Everson RB & Ames BN (1997). Folate deficiency causes uracil micincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage. Proc Natl Acad Sci U S A 94:3290-3295 https://doi.org/10.1073/pnas.94.7.3290
  8. Bottiglieri T, Hyland K & Reynolds EH (1994). The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 48:137-152 https://doi.org/10.2165/00003495-199448020-00002
  9. Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW & Reynolds EH (2000). Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 69:228-232 https://doi.org/10.1136/jnnp.69.2.228
  10. Bryan J, Calvaresi E & Hughes D (2002). Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr 132:1345-1356 https://doi.org/10.1093/jn/132.6.1345
  11. Buehring KU, Tamura T & Stockstad ELR (1974). Folate coenzymes of Lactobacillus casei and Streptococcus faecalis. J Biol Chem 249:1081
  12. Chen KJ, Pan WH, wang FL, Wei IL, Shaw NS & Lin BF (2005). Association of B vitamins status and homocysteine levels in elderly Taiwanese. Asia Pac J Clin Nutr 14:250-255
  13. Dakshinamurti K, Paulose CS & Siow YL (1985). Neurobiology of pyridoxine. In: Reynolds RD & Leklem JE (Eds.), Vitamin B-6: Its Role in Health and Disease. p.99-121. Alan Riss, Inc., New York. USA
  14. Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB & Verhoef P (2007). Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomized, double blind, controlled trial. Lancet 369:208-216 https://doi.org/10.1016/S0140-6736(07)60109-3
  15. Duthie SJ, Whalley LJ, Collins AR, Leaper S, Berger K & Deary IJ (2002). Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 75:908-913 https://doi.org/10.1093/ajcn/75.5.908
  16. Fakhrzadeh H, Ghotbi S, Pourebrahim R, Nouri M, Heshmat R, bandarian F, Shafaee A & Larijani B (2006). Total plasma homocysteine, folate and vitamin B-12 status in healthy Iranian adults: The Tehran homocysteine survey (2003-2004): a crosssectional population based study. BMC Public Health 6:29-37 https://doi.org/10.1186/1471-2458-6-29
  17. Feng L, Ng TP, Chuah L, Niti M & Kua EH (2006). Homocysteine, folate, and vitamin B-12 and cognitive performance in older Chinese adults: findings from the Singapore Longitudinal Ageing Study. Am J Clin Nutr 84:1506-1512 https://doi.org/10.1093/ajcn/84.6.1506
  18. Goodwin JS, Goodwin JM & Garry PJ (1983). Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA 249:2917 https://doi.org/10.1001/jama.249.21.2917
  19. Gospe SM Jr, Gietzen DW, Summers PJ, Lunetta JM, Miller JW, Selhub J, Ellis WG & Clifford AJ (1995). Behavioral and neurochemical changes in folate-deficient mice. Physiol Behav 58:935-941 https://doi.org/10.1016/0031-9384(95)00156-D
  20. Haller J, Wegggemans RM, Ferry M & Guigoz Y (1996). Mental health: Minimental state examination and geriatric depression score of elderly Europeans in the SENECA study of 1993. Eur J Clin Nutr 50:S112-S116
  21. Hassing L, Wahlin A, Winblad B & Bäckman L (1999). Further evidence on the effects of vitamin B12 and folate levels on episodic memory functioning: a population-based study of healthy very old adults. Biol Psychiatry 45:1472-1480 https://doi.org/10.1016/S0006-3223(98)00234-0
  22. Heaton RK (1981). A Manual for the Wisconsin Card Sorting Test. Odessa, FL. Psychological Assessment Resources, Inc. USA
  23. Herbert V (1987). The 1986 Herman Award Lecture. Nutriton science as a continually unfolding : the folate and vitamin B-12 paradigm. Am J Clin Nutr 48:387-402
  24. Hirata F & Axelrod J (1980). Phospholipid methylation and biological signal transmission. Science 209:1082-1090 https://doi.org/10.1126/science.6157192
  25. Joosten E, van den Berg A, Riezler R, Naurath HJ, Lindenbaum J, Stabler SP & Allen RH (1993). Metabolic evidence that deficiencies of vitamin B-12 (cobalamine), folate, and vitamin B-6 occur commonly in elderly people. Am J Clin Nutr 58:468-476 https://doi.org/10.1093/ajcn/58.4.468
  26. LaRue A, Koehler KM, Wayne SJ, Chiulli SJ, Haaland KY & Garry PJ (1997). Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment. Am J Clin Nutr 65:20-29 https://doi.org/10.1093/ajcn/65.1.20
  27. Leklem JE (1990). Vitamin B-6: A status report. J Nutr 120:1503-1507 https://doi.org/10.1093/jn/120.suppl_11.1503
  28. Lim HS & Heo YR (2002). Plasma total homocysteine, folate and vitamin B-12 status in Korean adults. J Nutr Sci Vitaminol 48:290-297 https://doi.org/10.3177/jnsv.48.290
  29. Lindeman RD, Romero LJ, Koehler KM, Liang HC, LaRue A, Baumgartner RM & Garry PJ (2000). Serum vitamin B-12, C and folate concentrations in the New Mexico elder health survey; correlations with cognitive and affective functions. J Am Coll Nutr 19:68-76 https://doi.org/10.1080/07315724.2000.10718916
  30. Luchsinger JA, Tang M-X, Miller J, Green R & Mayeux R (2007). Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol 64:86-92 https://doi.org/10.1001/archneur.64.1.86
  31. Maj M, D'Elia L, Satz P, Janssen R, Zaudig M, Uchiyama C, Starace F, Galderisi S & Chervinsky A (1993). Evaluation of three new neuropsychological tests designed to minimize cultural bias in the assessment of HIV-1-seropositive persons: a WHO study. Arch Clin Neuropsychol 8:123 https://doi.org/10.1016/0887-6177(93)90030-5
  32. Maxwell CJ, Hogan DB & Ebly EM (2002). Serum folate levels and subsequent adverse cerebrovascular outcomes in elderly persons. Dement Geriatr Cogn Disord 13:225-234 https://doi.org/10.1159/000057701
  33. Nilsson K, Gustafson L & Hultberg B (2001). Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int J Geriatr Psychiatry 16:609-614 https://doi.org/10.1002/gps.388
  34. Ramos MI, Allen LH, Mungas DM, Jagust WJ, Haan MN, Green R & Miller JW (2005). Low folate status is associated with impaired cognitive function and dementia in the Sacramento Area Latino Study on Aging. Am J Clin Nutr 82:1346-1352
  35. Riggs KM, Spiro A, III, Tucker K & Rush D (1996). Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 63:306 https://doi.org/10.1093/ajcn/63.3.306
  36. Rosenberg IH & Miller JW (1992). Nutritional factors in physical and cognitive functions of elderly people. Am J Clin Nutr 55:1237S-1243S https://doi.org/10.1093/ajcn/55.6.1237S
  37. Ruff RM & Parker SB (1993). Gender- and age-specifics changes in motor speed and eye-hand coordination in adults: normative values for the Finger Tapping and Grooved Pegboard Tests. Percept Mot Skills 76:1219 https://doi.org/10.2466/pms.1993.76.3c.1219
  38. Sauberlich HE, Judd JH, Nichoald GE, Broquist HP & Darby WJ (1972). Application of the erythrocyte glutathione reductase assay in evaluating riboflavin nutritional status in a high school student population. Am J Clin Nutr 25:756-762 https://doi.org/10.1093/ajcn/25.8.756
  39. Scott JM, Molloy AM, Kennedy DG, Kennedy S & Weir DG (1994). Effects of disruption of transmethylation in the central nerous system: an animal model. Acta Neurol Scand 154S:27 https://doi.org/10.1111/j.1600-0404.1994.tb05406.x
  40. Sheu KF, Calingasan NY, Lindsay JG & Gibson GE (1998). Immunochemical characterization of the deficiency of the alphaketoglutarate dehydrogenase complex in thiamine-deficient rat brain. J Neurochem 70:1143-1150 https://doi.org/10.1046/j.1471-4159.1998.70031143.x
  41. Smith AD (2002). Homocysteine, B vitamins, and cognitive deficit in the elderly. Am J Clin Nutr 75:785-786 https://doi.org/10.1093/ajcn/75.5.785
  42. Snowdon DA, Tully CL, Smith CD, Riley KP & Markesbery WR (2000). Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun Study. Am J Clin Nutr 71:993-998 https://doi.org/10.1093/ajcn/71.4.993
  43. Sommer BR, Hoff AL & Costa M (2003). Folic acid supplementation in dementia: a preliminary report. J Geriatr Psychiatry Neurol 16:156-159 https://doi.org/10.1177/0891988703256052
  44. Tanphaichitr B, Vimokesant SL, Dhanamitta S & Valyasevi A (1970). Clinical and biochemical studies of adult beriberi. Am J Clin Nutr 23:1017-1026 https://doi.org/10.1093/ajcn/23.8.1017
  45. Tettamanti M, Garrì MT, Nobili A, Riva E & Lucca U (2006). Low folate and the risk of cognitive and functional deficits in the very old: the Monzino 80-plus study. J Am Coll Nutr 25:502-508 https://doi.org/10.1080/07315724.2006.10719565
  46. Varela-Moreiras G & Selhub J (1992). Long-term folate deficiency alters folate content and distribution differentially in rat tissues. J Nutr 122:986-991 https://doi.org/10.1093/jn/122.4.986
  47. Wagner C (1995). Biochemical role of folate in cellular metabolism. In: Bailey LB (Ed.), Folate in Health and Disease. p.23-43. Marcel Dekker, Inc., New York. USA
  48. Wahlin A, Fahlander K, Wahlin T-B, Bunce D & Backman L (2008). Vitamin B status and cognitive perfomance in preclinical and clinical Alzheimer’s disease: Data form The Kungsholmen Project. Dementia and Geriatr Cogn Disord 25:23-31 https://doi.org/10.1159/000111129
  49. Wahlin A, Hill RD, Winblad B & Backman L (1996). Effects on serum vitamin B12 and folate status on episodic memory performance in very old age: a population-based study. Psychol Aging 11:487-496 https://doi.org/10.1037/0882-7974.11.3.487
  50. Wechsler D (1981). WAIS-R Manual. The Psychological Corporation, San Antonio, TX. USA
  51. Wechsler D (1987). Wechsler Memory Scale-Revised Manual. The Psychological Corporation, San Antonio, TX. USA