Total serum homocysteine levels do not identify cognitive dysfunction in multimorbid elderly patients

  • S. Hengstermann
  • G. Laemmler
  • A. Hanemann
  • A. Schweter
  • E. Steinhagen-Thiessen
  • A. Lun
  • R. -J. Schulz
Geriatric Science

Abstract

Objectives: Total blood homocysteine (Hcys) and folate levels have been investigated in association with cognitive dysfunction in healthy but not in multimorbid elderly patients. We hypothesized that total serum Hcys is an adequate marker to identify multimorbid elderly patients with cognitive dysfunction assessed by the Short Cognitive Performance Test (SKT) and Mini-Mental State Examination (MMSE).Design: Cross-sectional study.Setting: The study center was an acute geriatric hospital.Participants: A total of 189 multimorbid elderly patients were recruited.Methods: Cognitive dysfunction was determined according to the SKT and MMSE. Biochemical parameters (Hcys, folate, vitamin B12, hemoglobin), nutritional status (BMI, Mini Nutritional Assessment, nutritional intake), and activities of daily living were assessed.Results: According to the SKT, 25.4% of patients showed no cerebral cognitive dysfunction, 21.2% had suspected incipient cognitive dysfunction, 12.7% showed mild cognitive dysfunction, 9.0% had moderate cognitive dysfunction, and 31.7% of patients were demented. The median plasma Hcys value was elevated by ≈20% in multimorbid elderly patients, independent of cognitive dysfunction. Serum folate and vitamin B12 concentrations were within normal ranges. We did not find significant differences in nutritional status, activities of daily living, numbers of diseases or medications, or selected biochemical parameters between the SKT groups.Conclusion: Elevated serum Hcys levels with normal plasma folate and vitamin B12 concentrations were observed in multimorbid elderly patients. The plasma Hcys level did not appear to be an important biological risk factor for cognitive dysfunction in multimorbid geriatric patients.

Key words

Homocysteine folate cognitive dysfunction multimorbid elderly 

References

  1. 1.
    Rosenberg IH, Miller JW. Nutritional factors in physical and cognitive functions of elderly people. Am J Clin Nutr. 1992;55(6) Suppl: 1237S-243S. Review.PubMedGoogle Scholar
  2. 2.
    Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55(11): 1449–55.PubMedCrossRefGoogle Scholar
  3. 3.
    Stampfer MJ, Malinow MR, Willett WC et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA. 1992;19;268(7): 877–81.CrossRefGoogle Scholar
  4. 4.
    Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet. 1995; 346(8987): 1395–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Blom HJ. Determinants of plasma homocysteine. Am J Clin Nutr. 1998;67(2): 188–9.PubMedGoogle Scholar
  6. 6.
    Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Scihub J. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr. 2001;73(3): 613–21.PubMedGoogle Scholar
  7. 7.
    Schulz RJ. Homocysteine as a biomarker for cognitive dysfunction in the elderly. Curr Opin Nutr Metab Care. 2007; 10: 718–723.CrossRefGoogle Scholar
  8. 8.
    Crystal HA, Ortof E, Frishman WH, Gruber A, Hershman D, Aronson M. Serum vitamin B12 levels and incidence of dementia in a healthy elderly population: a report from the Bronx Longitudinal Aging Study. J Am Geriatr Soc. 1994;42(9): 933–6.PubMedGoogle Scholar
  9. 9.
    Metz J, Bell AH, Flicker L, Bottiglieri T et al. The significance of subnormal serum vitamin B12 concentration in older people: a case control study. J Am Geriatr Soc. 1996;44(11): 1355–61.PubMedGoogle Scholar
  10. 10.
    Riggs KM, Spiro A 3rd, Tucker K, Rush D. Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr. 1996;63(3): 306–14.PubMedGoogle Scholar
  11. 11.
    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 Jan;65(1): 20–9.PubMedGoogle Scholar
  12. 12.
    Wahlin A, Hill RD, Winblad B, Backman L. Effects of serum vitamin B12 and folate status on episodic memory performance in very old age: a population-based study. Psychol Aging. 1996;11(3): 487–96.PubMedCrossRefGoogle Scholar
  13. 13.
    Andersson A, Brattstrom L, Israelsson B, Isaksson A, Hamfelt A, Hultberg B. Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status. Eur J Clin Invest. 1992;22(2): 79–87.PubMedCrossRefGoogle Scholar
  14. 14.
    Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993; 270(22): 2693–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Saw SM, Yuan JM, Ong CN, Arakawa K, Lee HP, Coetzee GA, Yu MC. Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore. Am J Clin Nutr. 2001;73(2): 232–9.PubMedGoogle Scholar
  16. 16.
    Garcia A, Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ. 2004;171(8): 897–904. Review.PubMedGoogle Scholar
  17. 17.
    Budge M, Johnston C, Hogervorst E et al. Plasma total homocysteine and cognitive performance in a volunteer elderly population. Ann N Y Acad Sci. 2000;903: 407–10.PubMedCrossRefGoogle Scholar
  18. 18.
    Duthie SJ, Whalley LJ, Collins AR, Leaper S, Berger K, Deary IJ. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr. 2002;75(5): 908–13PubMedGoogle Scholar
  19. 19.
    Teunissen CE, Blom AH, Van Boxtel MP et al. Homocysteine: a marker for cognitive performance? A longitudinal follow-up study. J Nutr Health Aging. 2003;7(3): 153–9.PubMedGoogle Scholar
  20. 20.
    Kalmijn S, Launer LJ, Lindemans J, Bots ML, Hofman A, Breteler MM. Total homocysteine and cognitive decline in a community-based sample of elderly subjects: the Rotterdam Study. Am J Epidemiol. 1999; 150(3): 283–9.PubMedGoogle Scholar
  21. 21.
    Ravaglia G, Forti P, Maioli F et al. Blood homocysteine and vitamin B levels are not associated with cognitive skills in healthy normally ageing subjects. J Nutr Health Aging. 2000;4(4): 218–22.PubMedGoogle Scholar
  22. 22.
    Erzigkeit H. SKT: The SKT: a short cognitive performance test as an instrument for the assessment of clinical efficacy of cognition enhancers, In: Bergener M, Reisberg B (eds.). Diagnosis and treatment of senile dementia. New York: Springer-Verlag; 1989: 164–174Google Scholar
  23. 23.
    Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3): 189–98.PubMedCrossRefGoogle Scholar
  24. 24.
    Chumlea WC, Guo S. Equations for predicting stature in white and black elderly individuals. J Gerontol. 1992;47: M197-M203PubMedGoogle Scholar
  25. 25.
    Guigoz Y, Vellas B, Garry PJ. Mini Nutritional Assessment: A practical assessment tool for grading the nutritional state of elderly patients. Facts and Research in Gerontology. 1994; Suppl. 2: 15–59.Google Scholar
  26. 26.
    Harris JA, Benedict FG. A biometric study of human basal metabolism. Proc Natl Acad Sci. USA 1918;4(12): 370–3.PubMedCrossRefGoogle Scholar
  27. 27.
    Mahoney FI, Barthel DW. Functional evaluation: The Bathel Index. Md State Med J. 1965; 14: 61–5.PubMedGoogle Scholar
  28. 28.
    Jacques PF, Rosenberg IH, Rogers G et al. Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 1999; 69(3): 482–9.PubMedGoogle Scholar
  29. 29.
    Strassburg A, Krems C, Luhrmann PM et al. Effect of age on plasma homocysteine concentrations in young and elderly subjects considering serum vitamin concentrations and different lifestyle factors. Int J Vitam Nutr Res. 2004;74(2): 129–36.PubMedCrossRefGoogle Scholar
  30. 30.
    Huerta JM, Gonzalez S, Vigil E et al. Folate and cobalamin synergistically decrease the risk of high plasma homocysteine in a nonsupplemented elderly institutionalized population. ClinBiochem. 2004;37(10): 904–10.Google Scholar
  31. 31.
    Wolters M, Hermann S, Hahn A. B vitamin status and concentrations of homocysteine and methylmalonic acid in elderly German women. Am J Clin Nutr. 2003;78(4): 765–72.PubMedGoogle Scholar
  32. 32.
    Lindenbaum J, Healton EB, Savage DG et al. Neuropsychiatrie disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. 1988. Nutrition. 1995; 11(2): 181PubMedGoogle Scholar
  33. 33.
    Morris MS, Jacques PF, Rosenberg IH, Selhub J; National Health and Nutrition Examination Survey. Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 2001;73(5): 927–33.PubMedGoogle Scholar
  34. 34.
    Seshadri S, Beiser A, Selhub J et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346(7): 476–83.PubMedCrossRefGoogle Scholar
  35. 35.
    Hernanz A, Fernandez-Vivancos E, Montiel C, Vazquez JJ, Arnalich F. Changes in the intracellular homocysteine and glutathione content associated with aging. Life Sci. 2000;67(11): 1317–24.PubMedCrossRefGoogle Scholar
  36. 36.
    Garry PJ, Goodwin JS, Hunt WC. Folate and vitamin B12 status in a healthy elderly population. J Am Geriatr Soc. 1984;32(10): 719–26.PubMedGoogle Scholar
  37. 37.
    Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994;60(1): 2–11.PubMedGoogle Scholar
  38. 38.
    Allen RH, Stabler SP, Savage DG, Lindenbaum J. Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. FASEB J. 1993;7(14): 1344–53. Review.PubMedGoogle Scholar
  39. 39.
    Ventura P, Panini R, Verlato C, Scarpetta G, Salvioli G. Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects. Metabolism. 2001; 50: 1466–71.PubMedCrossRefGoogle Scholar
  40. 40.
    Frosst P, Blom HJ, Milos R et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1): 111–3.PubMedCrossRefGoogle Scholar
  41. 41.
    Russo GT, Friso S, Jacques PF et al; Framingham Offspring Study Cohort. Age and gender affect the relation between methylenetetrahydrofolate reductase C677T genotype and fasting plasma homocysteine concentrations in the Framingham Offspring Study Cohort. J Nutr. 2003; 133(11): 3416–21.PubMedGoogle Scholar
  42. 42.
    Chanarin I, Metz J. Diagnosis of cobalamin deficiency: the old and the new. Br J Haematol. 1997;97(4): 695–700.PubMedCrossRefGoogle Scholar
  43. 43.
    Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG, Lindenbaum J. Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest. 1988;81(2): 466–74.PubMedCrossRefGoogle Scholar
  44. 44.
    Kim JM, Stewart R, Kim SW, Yang SJ, Shin HY, Shin, IS, Yoon JS. Changes in folate, vitamin B12, and homocysteine associated with incident dementia. J Neurol Neurosurg Psychiatry. 2008; Feb 5 (in print).Google Scholar
  45. 45.
    Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolies J, Katan MB, Verhoef P. 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 Jan 20;369(9557): 208–16.PubMedCrossRefGoogle Scholar
  46. 46.
    Raeder S, Landaas S, Laake K, et al. Homocysteine measurements in geriatric patients. Scand J Clin Lab Invest. 2006; 66: 309–315.PubMedCrossRefGoogle Scholar
  47. 47.
    La Rue A, Koehler KM, Wayne SJ, et al. Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment. Am J Clin Nutr. 1997; 65: 20–29.PubMedGoogle Scholar
  48. 48.
    Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999 May 13;340(19): 1449–54PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag France and Serdi Éditions 2008

Authors and Affiliations

  • S. Hengstermann
    • 1
  • G. Laemmler
    • 1
  • A. Hanemann
    • 1
  • A. Schweter
    • 1
  • E. Steinhagen-Thiessen
    • 1
  • A. Lun
    • 2
  • R. -J. Schulz
    • 1
  1. 1.Campus Virchow-Klinikum, Research Group on Geriatrics at “Ev. Geriatriezentrum Berlin”Charité - Universitätsmedizin BerlinBerlinGermany
  2. 2.Campus Virchow-Klinikum, Institute of Laboratory MedicineCharité - Universitätsmedizin BerlinBerlinGermany

Personalised recommendations