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Vol. 32, No. 1, 2009
Issue release date: December 2008
Free Access
Neuroepidemiology 2009;32:40–46
(DOI:10.1159/000170905)

Relation of Hemoglobin to Level of Cognitive Function in Older Persons

Shah R.C.a, d · Wilson R.S.a, c, e · Tang Y.b, f · Dong X.f · Murray A.g · Bennett D.A.a, c
aRush Alzheimer’s Disease Center, bRush Institute for Healthy Aging and Departments of cNeurological Sciences, dFamily Medicine, ePsychology and fInternal Medicine, Rush University Medical Center, Chicago, Ill., and gDepartment of Medicine, Hennepin County Medical Center, Minneapolis, Minn., USA
email Corresponding Author

Abstract

Background: While decreased hemoglobin concentration is common in the elderly, the relationship of the entire range of hemoglobin concentrations with cognitive function is not well understood. Methods: Cross-sectional analyses were conducted utilizing data from community-dwelling, older persons participating in the Rush Memory and Aging Project. Proximate to first available hemoglobin measurement, 21 cognitive tests were administered to measure global cognitive function along with semantic memory, episodic memory, working memory, perceptual speed and visuospatial abilities. Results: For 793 participants without clinical dementia, stroke or Parkinson’s disease, the mean age was 81.0 years (SD = 7.2); 595 (75%) were women, and 94% were white. The mean hemoglobin concentration was 13.3 g/dl (SD = 1.3). 17% of the cohort had anemia. Using linear regression models adjusted for age, education, gender, body mass index, mean corpuscular volume and glomerular filtration rate, both low and high hemoglobin levels were associated with lower global cognitive function (parameter estimate = –0.015, SE = 0.007, p = 0.019). Low and high hemoglobin levels were associated with worse performance on semantic memory (parameter estimate = –0.201, SE = 0.008, p = 0.010) and perceptual speed (parameter estimate = –0.030, SE = 0.010, p = 0.004), but not the other specific cognitive functions. Conclusions: Low and high hemoglobin concentrations in older persons are associated with a lower level of cognitive function in old age, particularly in semantic memory and perceptual speed.


 goto top of outline Key Words

  • Hemoglobin
  • Anemia
  • Cognition
  • Elderly
  • Gender
  • Cross-sectional study

 goto top of outline Abstract

Background: While decreased hemoglobin concentration is common in the elderly, the relationship of the entire range of hemoglobin concentrations with cognitive function is not well understood. Methods: Cross-sectional analyses were conducted utilizing data from community-dwelling, older persons participating in the Rush Memory and Aging Project. Proximate to first available hemoglobin measurement, 21 cognitive tests were administered to measure global cognitive function along with semantic memory, episodic memory, working memory, perceptual speed and visuospatial abilities. Results: For 793 participants without clinical dementia, stroke or Parkinson’s disease, the mean age was 81.0 years (SD = 7.2); 595 (75%) were women, and 94% were white. The mean hemoglobin concentration was 13.3 g/dl (SD = 1.3). 17% of the cohort had anemia. Using linear regression models adjusted for age, education, gender, body mass index, mean corpuscular volume and glomerular filtration rate, both low and high hemoglobin levels were associated with lower global cognitive function (parameter estimate = –0.015, SE = 0.007, p = 0.019). Low and high hemoglobin levels were associated with worse performance on semantic memory (parameter estimate = –0.201, SE = 0.008, p = 0.010) and perceptual speed (parameter estimate = –0.030, SE = 0.010, p = 0.004), but not the other specific cognitive functions. Conclusions: Low and high hemoglobin concentrations in older persons are associated with a lower level of cognitive function in old age, particularly in semantic memory and perceptual speed.

Copyright © 2008 S. Karger AG, Basel


 goto top of outline References
  1. Woodman R, Ferrucci L, Guralnik J: Anemia in older adults. Curr Opin Hematol 2005;12:123–128.
  2. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC: Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 2004;104:2263– 2268.
  3. Chaves PH, Ashar B, Guralnik JM, Fried LP: Looking at the relationship between hemoglobin concentration and prevalent mobility difficulty in older women: should the criteria currently used to define anemia in older people be reevaluated? J Am Geriatr Soc 2002;50:1257–1264.
  4. Penninx BW, Pahor M, Woodman RC, Guralnik JM: Anemia in old age is associated with increased mortality and hospitalization. J Gerontol A Biol Sci Med Sci 2006;51:474–479.
  5. Denny SD, Kuchibhatla MN, Cohen HJ: Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med 2006;119:327–334.
  6. Chaves PH, Carlson MC, Ferrucci L, Guralnik JM, Serba R, Fried LP: Association between mild anemia and executive function impairment in community-dwelling older women: the Women’s Health and Aging Study II. J Am Geriatr Soc 2006;54:1429–1435.
  7. Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PH, Newman AB, Cushman M: A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med 2005;165:2214–2220.
  8. Bennett DA, Schneider JA, Buchman AS, Mendes de Leon C, Bienias JL, Wilson RS: The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort. Neuroepidemiology 2005;25:163–175.
  9. 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;12:189–198.
  10. Goodglass H, Kaplan E: The Assessment of Aphasia and Related Disorders. Philadelphia, Lea & Febiger, 1972.
  11. Welsh KA, Butters N, Mohs RC, Beekly D, Edland S, Fillenbaum G, Heyman A: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). V. A normative study of the neuropsychological battery. Neurology 1994;44:609–614.
  12. Wechsler D: Wechsler Memory Scale – Revised Manual. San Antonio, Psychological Corp, 1987.
  13. Albert M, Smith L, Scherr P, Taylor JO, Evans DA, Funkenstein HH: Use of brief cognitive tests to identify individuals in the community with clinically diagnosed Alzheimer’s disease. Int J Neurosci 1991;57:167–178.
  14. Kaplan EF, Goodglass H, Weintraub S: The Boston Naming Test. Philadelphia, Lea & Febiger, 1983.
  15. Nelson HE: National Adult Reading Test (NART) Manual. Windsor, NFER-Nelson Publishing Co, 1982.
  16. Cooper JA, Sager HJ: Incidental and intentional recall in Parkinson’s disease: an account based on diminished attentional resources. J Clin Exp Neuropsychol 1993;15:713–731.
  17. Smith A: Symbol Digit Modalities Test Manual – Revised. Los Angeles, Western Psychological Services, 1982.
  18. Trenerry MR, Crosson B, DeBoe J, et al: The Stroop Neuropsychological Screening Test. Odessa, Psychological Assessment Resources, 1989.
  19. Benton AL, Sivan AB, Hamsher K, et al: Contributions to Neuropsychological Assessment, ed 2. New York, Oxford University Press, 1994.
  20. Raven JC, Court JH, Raven J: Manual for Raven’s Progressive Matrices and Vocabulary: Standard Progressive Matrices. Oxford, Oxford Psychologists’ Press, 1992.
  21. Wilson RS, Barnes LL, Krueger KR, Hoganson G, Bienias JL, Bennett DA: Early and late life cognitive activity and cognitive systems in old age. J Int Neuropsychol Soc 2005;11:400–407.
  22. World Health Organization: Nutritional anemias. Report of a WHO Scientific Group. World Health Organization Tech Rep Ser 405. Geneva, WHO, 1968.
  23. Featherman DL, Hauser RM: The measurement of occupation in social surveys; in Hauser RM, Featherman DL (eds): The Process of Stratification. Orlando, Academic Press, 1977, pp 51–80.
  24. Wilson RS, Scherr PA, Bienias JL, Mendes de Leon CF, Everson-Rose SA, Bennett DA, Evans DA: Socioeconomic characteristics of the community in childhood and cognition in old age. Exp Aging Res 2005;31:393–407.
  25. National Kidney Disease Educational Program: GFR calculators. http://www.nkdep.nih.gov/professionals/gfr_calculators/orig_con.htm (accessed February 21, 2007).
  26. National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 2002;39(suppl 1):S1–S266.
  27. Salive ME, Cornoni-Huntley J, Guralnik JM, Phillips CL, Wallace RB, Ostfeld AM, Cohen HJ: Anemia and hemoglobin levels in older persons: relationship with age, gender, and health status. J Am Geriatr Soc 1992;40:489–496.
  28. Hsu C-Y, McCulloch CE, Curhan GC: Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the third national health and nutrition examination survey. J Am Soc Nephrol 2002;13:504–510.
  29. Abramson JL, Jurkovitz CT, Vaccarino V, Weintraub WS, McClellan W: Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study. Kidney Int 2003;64:610–615.
  30. Gruppo Italiano Studio Policitemia: Polycythemia vera: the natural history of 1,213 patients followed for 20 years. Ann Intern Med 1995;123:656–664.
  31. Liesker JJ, Postma DS, Beukema RJ, ten Hacken NH, van der Molen T, Riemersma RA, van Zomeren EH, Kerstjens HA: Cognitive performance in patients with COPD. Respir Med 2004;98:351–356.
  32. Antonelli Incalzi R, Marra C, Giordano A, Calcagni ML, Cappa A, Basso S, Pagliari G, Fuso L: Cognitive impairment in chronic obstructive pulmonary disease – a neuropsychological and SPECT study. J Neurol 2003;250:325–332.
  33. Kozora E, Filley CM, Julian LJ, Cullum CM: Cognitive functioning in patients with chronic obstructive pulmonary disease and mild hypoxemia compared with patients with mild Alzheimer disease and normal controls. Neuropsychiatry Neuropsychol Behav Neurol 1999;12:178–183.
  34. Nangaku M, Inagi R, Miyata T, Fujita T: Hypoxia and hypoxia-inducible factor in renal disease. Nephron Exp Nephrol 2008;110: e1–e7.
  35. Tuder RM, Yun JH, Bhunia A, Fijalkowska I: Hypoxia and chronic lung disease. J Mol Med 2007;85:1317–1324.
  36. Hasselblatt M, Ehrenreich, Siren AL: The brain erythropoietin system and its potential for therapeutic exploitation in brain disease. J Neurosurg Anesthesiol 2006;18:132–138.
  37. Maiesi K, Li F, Chong ZZ: New avenues of exploration for erythropoietin. JAMA 2005;293:90–95.

    External Resources

  38. Droge W, Schipper HM: Oxidative stress and aberrant signaling in aging and cognitive decline. Aging Cell 2007;6:361–370.

 goto top of outline Author Contacts

Dr. Raj C. Shah
Rush Alzheimer’s Disease Center
600 South Paulina, Room 1038
Chicago, IL 60612 (USA)
Tel. +1 312 563 2902, Fax +1 312 563 4154, E-Mail Raj_C_Shah@rush.edu


 goto top of outline Article Information

Received: March 6, 2008
Accepted: August 19, 2008
Published online: November 12, 2008
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 3, Number of References : 38


 goto top of outline Publication Details

Neuroepidemiology

Vol. 32, No. 1, Year 2009 (Cover Date: December 2008)

Journal Editor: Feigin V.L. (Auckland), Logroscino G. (Boston, MA), Hofman A. (Rotterdam), Donnan G. (Heidelberg Heights, Vic.)
ISSN: 0251–5350 (Print), eISSN: 1423–0208 (Online)

For additional information: http://www.karger.com/NED


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: While decreased hemoglobin concentration is common in the elderly, the relationship of the entire range of hemoglobin concentrations with cognitive function is not well understood. Methods: Cross-sectional analyses were conducted utilizing data from community-dwelling, older persons participating in the Rush Memory and Aging Project. Proximate to first available hemoglobin measurement, 21 cognitive tests were administered to measure global cognitive function along with semantic memory, episodic memory, working memory, perceptual speed and visuospatial abilities. Results: For 793 participants without clinical dementia, stroke or Parkinson’s disease, the mean age was 81.0 years (SD = 7.2); 595 (75%) were women, and 94% were white. The mean hemoglobin concentration was 13.3 g/dl (SD = 1.3). 17% of the cohort had anemia. Using linear regression models adjusted for age, education, gender, body mass index, mean corpuscular volume and glomerular filtration rate, both low and high hemoglobin levels were associated with lower global cognitive function (parameter estimate = –0.015, SE = 0.007, p = 0.019). Low and high hemoglobin levels were associated with worse performance on semantic memory (parameter estimate = –0.201, SE = 0.008, p = 0.010) and perceptual speed (parameter estimate = –0.030, SE = 0.010, p = 0.004), but not the other specific cognitive functions. Conclusions: Low and high hemoglobin concentrations in older persons are associated with a lower level of cognitive function in old age, particularly in semantic memory and perceptual speed.



 goto top of outline Author Contacts

Dr. Raj C. Shah
Rush Alzheimer’s Disease Center
600 South Paulina, Room 1038
Chicago, IL 60612 (USA)
Tel. +1 312 563 2902, Fax +1 312 563 4154, E-Mail Raj_C_Shah@rush.edu


 goto top of outline Article Information

Received: March 6, 2008
Accepted: August 19, 2008
Published online: November 12, 2008
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 3, Number of References : 38


 goto top of outline Publication Details

Neuroepidemiology

Vol. 32, No. 1, Year 2009 (Cover Date: December 2008)

Journal Editor: Feigin V.L. (Auckland), Logroscino G. (Boston, MA), Hofman A. (Rotterdam), Donnan G. (Heidelberg Heights, Vic.)
ISSN: 0251–5350 (Print), eISSN: 1423–0208 (Online)

For additional information: http://www.karger.com/NED


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Woodman R, Ferrucci L, Guralnik J: Anemia in older adults. Curr Opin Hematol 2005;12:123–128.
  2. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC: Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 2004;104:2263– 2268.
  3. Chaves PH, Ashar B, Guralnik JM, Fried LP: Looking at the relationship between hemoglobin concentration and prevalent mobility difficulty in older women: should the criteria currently used to define anemia in older people be reevaluated? J Am Geriatr Soc 2002;50:1257–1264.
  4. Penninx BW, Pahor M, Woodman RC, Guralnik JM: Anemia in old age is associated with increased mortality and hospitalization. J Gerontol A Biol Sci Med Sci 2006;51:474–479.
  5. Denny SD, Kuchibhatla MN, Cohen HJ: Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med 2006;119:327–334.
  6. Chaves PH, Carlson MC, Ferrucci L, Guralnik JM, Serba R, Fried LP: Association between mild anemia and executive function impairment in community-dwelling older women: the Women’s Health and Aging Study II. J Am Geriatr Soc 2006;54:1429–1435.
  7. Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PH, Newman AB, Cushman M: A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med 2005;165:2214–2220.
  8. Bennett DA, Schneider JA, Buchman AS, Mendes de Leon C, Bienias JL, Wilson RS: The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort. Neuroepidemiology 2005;25:163–175.
  9. 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;12:189–198.
  10. Goodglass H, Kaplan E: The Assessment of Aphasia and Related Disorders. Philadelphia, Lea & Febiger, 1972.
  11. Welsh KA, Butters N, Mohs RC, Beekly D, Edland S, Fillenbaum G, Heyman A: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). V. A normative study of the neuropsychological battery. Neurology 1994;44:609–614.
  12. Wechsler D: Wechsler Memory Scale – Revised Manual. San Antonio, Psychological Corp, 1987.
  13. Albert M, Smith L, Scherr P, Taylor JO, Evans DA, Funkenstein HH: Use of brief cognitive tests to identify individuals in the community with clinically diagnosed Alzheimer’s disease. Int J Neurosci 1991;57:167–178.
  14. Kaplan EF, Goodglass H, Weintraub S: The Boston Naming Test. Philadelphia, Lea & Febiger, 1983.
  15. Nelson HE: National Adult Reading Test (NART) Manual. Windsor, NFER-Nelson Publishing Co, 1982.
  16. Cooper JA, Sager HJ: Incidental and intentional recall in Parkinson’s disease: an account based on diminished attentional resources. J Clin Exp Neuropsychol 1993;15:713–731.
  17. Smith A: Symbol Digit Modalities Test Manual – Revised. Los Angeles, Western Psychological Services, 1982.
  18. Trenerry MR, Crosson B, DeBoe J, et al: The Stroop Neuropsychological Screening Test. Odessa, Psychological Assessment Resources, 1989.
  19. Benton AL, Sivan AB, Hamsher K, et al: Contributions to Neuropsychological Assessment, ed 2. New York, Oxford University Press, 1994.
  20. Raven JC, Court JH, Raven J: Manual for Raven’s Progressive Matrices and Vocabulary: Standard Progressive Matrices. Oxford, Oxford Psychologists’ Press, 1992.
  21. Wilson RS, Barnes LL, Krueger KR, Hoganson G, Bienias JL, Bennett DA: Early and late life cognitive activity and cognitive systems in old age. J Int Neuropsychol Soc 2005;11:400–407.
  22. World Health Organization: Nutritional anemias. Report of a WHO Scientific Group. World Health Organization Tech Rep Ser 405. Geneva, WHO, 1968.
  23. Featherman DL, Hauser RM: The measurement of occupation in social surveys; in Hauser RM, Featherman DL (eds): The Process of Stratification. Orlando, Academic Press, 1977, pp 51–80.
  24. Wilson RS, Scherr PA, Bienias JL, Mendes de Leon CF, Everson-Rose SA, Bennett DA, Evans DA: Socioeconomic characteristics of the community in childhood and cognition in old age. Exp Aging Res 2005;31:393–407.
  25. National Kidney Disease Educational Program: GFR calculators. http://www.nkdep.nih.gov/professionals/gfr_calculators/orig_con.htm (accessed February 21, 2007).
  26. National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 2002;39(suppl 1):S1–S266.
  27. Salive ME, Cornoni-Huntley J, Guralnik JM, Phillips CL, Wallace RB, Ostfeld AM, Cohen HJ: Anemia and hemoglobin levels in older persons: relationship with age, gender, and health status. J Am Geriatr Soc 1992;40:489–496.
  28. Hsu C-Y, McCulloch CE, Curhan GC: Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the third national health and nutrition examination survey. J Am Soc Nephrol 2002;13:504–510.
  29. Abramson JL, Jurkovitz CT, Vaccarino V, Weintraub WS, McClellan W: Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study. Kidney Int 2003;64:610–615.
  30. Gruppo Italiano Studio Policitemia: Polycythemia vera: the natural history of 1,213 patients followed for 20 years. Ann Intern Med 1995;123:656–664.
  31. Liesker JJ, Postma DS, Beukema RJ, ten Hacken NH, van der Molen T, Riemersma RA, van Zomeren EH, Kerstjens HA: Cognitive performance in patients with COPD. Respir Med 2004;98:351–356.
  32. Antonelli Incalzi R, Marra C, Giordano A, Calcagni ML, Cappa A, Basso S, Pagliari G, Fuso L: Cognitive impairment in chronic obstructive pulmonary disease – a neuropsychological and SPECT study. J Neurol 2003;250:325–332.
  33. Kozora E, Filley CM, Julian LJ, Cullum CM: Cognitive functioning in patients with chronic obstructive pulmonary disease and mild hypoxemia compared with patients with mild Alzheimer disease and normal controls. Neuropsychiatry Neuropsychol Behav Neurol 1999;12:178–183.
  34. Nangaku M, Inagi R, Miyata T, Fujita T: Hypoxia and hypoxia-inducible factor in renal disease. Nephron Exp Nephrol 2008;110: e1–e7.
  35. Tuder RM, Yun JH, Bhunia A, Fijalkowska I: Hypoxia and chronic lung disease. J Mol Med 2007;85:1317–1324.
  36. Hasselblatt M, Ehrenreich, Siren AL: The brain erythropoietin system and its potential for therapeutic exploitation in brain disease. J Neurosurg Anesthesiol 2006;18:132–138.
  37. Maiesi K, Li F, Chong ZZ: New avenues of exploration for erythropoietin. JAMA 2005;293:90–95.

    External Resources

  38. Droge W, Schipper HM: Oxidative stress and aberrant signaling in aging and cognitive decline. Aging Cell 2007;6:361–370.