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Vol. 20, No. 1, 2005
Issue release date: June 2005
Section title: Original Research Article
Dement Geriatr Cogn Disord 2005;20:45–51
(DOI:10.1159/000085074)

Supplemental Use of Antioxidant Vitamins and Subsequent Risk of Cognitive Decline and Dementia

Maxwell C.J.a, b · Hicks M.S.a · Hogan D.B.a-c · Basran J.b · Ebly E.M.c
Departments of aCommunity Health Sciences, bMedicine, and cClinical Neurosciences, University of Calgary, Calgary, Canada
email Corresponding Author

Abstract

There are conflicting reports about the potential role of vitamin antioxidants in preventing and/or slowing the progression of various forms of cognitive impairment including Alzheimer’s disease (AD). We examined longitudinal data from the Canadian Study of Health and Aging, a population-based, prospective 5-year investigation of the epidemiology of dementia among Canadians aged 65+ years. Our primary objective was to examine the association between supplemental use of antioxidant vitamins and subsequent risk of significant cognitive decline (decrease in 3MS score of 10 points or more) among subjects with no evidence of dementia at baseline (n = 894). We also explored the relationship between vitamin supplement use and incident vascular cognitive impairment (VCI; including a diagnosis of vascular dementia, possible AD with vascular components and VCI but not dementia), dementia (all cases) and AD. After adjusting for potential confounding factors assessed at baseline, subjects reporting a combined use of vitamin E and C supplements and/or multivitamin consumption at baseline were significantly less likely (adjusted OR 0.51; 95% CI 0.29–0.90) to experience significant cognitive decline during a 5-year follow-up period. Subjects reporting any antioxidant vitamin use at baseline also showed a significantly lower risk for incident VCI (adjusted OR 0.34, 95% CI 0.13–0.89). A reduced risk for incident dementia or AD was not observed. Our findings suggest a possible protective effect for antioxidant vitamins in relation to cognitive decline but randomized controlled trials are required for confirmation.

© 2005 S. Karger AG, Basel


  

Key Words

  • Antioxidant vitamins
  • Cognitive decline
  • Dementia
  • Vascular cognitive impairment
  • Alzheimer’s disease

References

  1. Sano M, Ernesto C, Thomas RG, et al: A controlled trial of selegiline, α-tocopherol, or both as treatment for Alzheimer’s disease: The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997;336:1216–1222.
  2. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JCM, Breteler MMB: Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3223–3229.
  3. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA: Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002;287:3230–3237.
  4. Luchsinger JA, Tang M-X, Shea S, Mayeux R: Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol 2003;60:203–208.
  5. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JCS, for the Cache County Study Group: Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements. The Cache County Study. Arch Neurol 2004;61:82–88.
  6. Markesbery WR: The role of oxidative stress in Alzheimer disease. Arch Neurol 1999;56:1449–1452.
  7. Christen, Y: Oxidative stress and Alzheimer disease. Am J Clin Nutr 2000;71(suppl):621S–629S.
  8. Delanty N, Dichter MA: Antioxidant therapy in neurologic disease. Arch Neurol 2000;57:1265–1270.
  9. Misonou H, Morishima-Kawashima M, Ihara Y: Oxidative stress induces intracellular accumulation of amyloid β-protein (Aβ) in human neuroblastoma cells. Biochemistry 2000;39:6951–6959.
  10. Halliwell B: Role of free radicals in the neurodegenerative diseases. Therapeutic implications for antioxidant treatment. Drugs Aging 2001;18:685–716.
  11. Poon HF, Calabrese V, Scapagnini G, Butterfield DA: Free radicals: Key to brain aging and heme oxygenase as a cellular response to oxidative stress. J Gerontol A Biol Sci Med Sci 2004;59A:478–493.
  12. Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR: Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000;54:1265–1272.
  13. Morris MC, Beckett LA, Scherr PA, Hebert LE, Bennett DA, Field TS, Evans DA: Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord 1998;12:121–126.
  14. Morris MC, Evans DA, Bienias JL, Tangney CC, Wilson RS: Vitamin E and cognitive decline in older persons. Arch Neurol 2002;59:1125–1132.
  15. Teng EL, Chui HC: The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry 1987;48:314–318.
  16. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 3. Washington, American Psychiatric Association, 1987, pp 133–136.
  17. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984;34:939–944.
  18. World Health Organization: International Classification of Diseases, 10th revision: Clinical descriptions and diagnostic guidelines. Categories F00-F99, mental, behavioural and developmental disorders (1987 draft of chapter V). Geneva, World Health Organization, 1987, Rep No MNH/MEP/87.1 rev1.
  19. Canadian Study of Health and Aging Working Group: Canadian Study of Health and Aging: Study methods and prevalence of dementia. CMAJ 1994;150:899–913.
  20. The Canadian Study of Health and Aging Working Group: The incidence of dementia in Canada. Neurology 2000;55:66–73.
  21. Maxwell CJ, Hogan DB, Ebly EM: Serum folate levels and subsequent adverse cerebrovascular outcomes in elderly persons. Dement Geriatr Cogn Disord 2002;13:225–234.
  22. Maxwell CJ, Hogan DB, Ebly EM: Calcium-channel blockers and cognitive function in elderly people: Results from the Canadian Study of Health and Aging. CMAJ 1999;161:501–506.
  23. Rockwood K, Ebly E, Hachinski V, Hogan D: Presence and treatment of vascular risk factors in patients with vascular cognitive impairment. Arch Neurol 1997;54:33–39.
  24. Kelsey JL, Whittemore AS, Evans AS, Thompson WD: Methods in Observational Epidemiology, ed 2. New York, Oxford University Press, 1996.
  25. SAS Institute Inc: SAS User’s Guide, release 8.2 for Windows. Cary, SAS Institute Inc., 1999–2001.
  26. Tang M-X, Stern Y, Marder K, Bell K, Gurland B, Lantigua R, Andrews H, Feng L, Tycko B, Mayeux R: The APOE-ε4 allele and the risk of Alzheimer disease among African Americans, Whites and Hispanics. JAMA 1998;279:751–755.

  

Author Contacts

Dr. Colleen Maxwell
Community Health Sciences, University of Calgary
Heritage Medical Research Building, 3330 Hospital Drive N.W.
Calgary, Alberta T2N 4N1 (Canada)
Tel. +1 403 220 6557, Fax +1 403 270 7307, E-Mail maxwell@ucalgary.ca

  

Article Information

Accepted: December 17, 2004
Published online: April 12, 2005
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 2, Number of References : 26

  

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 20, No. 1, Year 2005 (Cover Date: Released June 2005)

Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420–8008 (print), 1421–9824 (Online)

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


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

There are conflicting reports about the potential role of vitamin antioxidants in preventing and/or slowing the progression of various forms of cognitive impairment including Alzheimer’s disease (AD). We examined longitudinal data from the Canadian Study of Health and Aging, a population-based, prospective 5-year investigation of the epidemiology of dementia among Canadians aged 65+ years. Our primary objective was to examine the association between supplemental use of antioxidant vitamins and subsequent risk of significant cognitive decline (decrease in 3MS score of 10 points or more) among subjects with no evidence of dementia at baseline (n = 894). We also explored the relationship between vitamin supplement use and incident vascular cognitive impairment (VCI; including a diagnosis of vascular dementia, possible AD with vascular components and VCI but not dementia), dementia (all cases) and AD. After adjusting for potential confounding factors assessed at baseline, subjects reporting a combined use of vitamin E and C supplements and/or multivitamin consumption at baseline were significantly less likely (adjusted OR 0.51; 95% CI 0.29–0.90) to experience significant cognitive decline during a 5-year follow-up period. Subjects reporting any antioxidant vitamin use at baseline also showed a significantly lower risk for incident VCI (adjusted OR 0.34, 95% CI 0.13–0.89). A reduced risk for incident dementia or AD was not observed. Our findings suggest a possible protective effect for antioxidant vitamins in relation to cognitive decline but randomized controlled trials are required for confirmation.

© 2005 S. Karger AG, Basel


  

Author Contacts

Dr. Colleen Maxwell
Community Health Sciences, University of Calgary
Heritage Medical Research Building, 3330 Hospital Drive N.W.
Calgary, Alberta T2N 4N1 (Canada)
Tel. +1 403 220 6557, Fax +1 403 270 7307, E-Mail maxwell@ucalgary.ca

  

Article Information

Accepted: December 17, 2004
Published online: April 12, 2005
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 2, Number of References : 26

  

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 20, No. 1, Year 2005 (Cover Date: Released June 2005)

Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420–8008 (print), 1421–9824 (Online)

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


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Received: 12/17/2004
Published online: 6/6/2005
Issue release date: June 2005

Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 2

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

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


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. Sano M, Ernesto C, Thomas RG, et al: A controlled trial of selegiline, α-tocopherol, or both as treatment for Alzheimer’s disease: The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997;336:1216–1222.
  2. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JCM, Breteler MMB: Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3223–3229.
  3. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA: Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002;287:3230–3237.
  4. Luchsinger JA, Tang M-X, Shea S, Mayeux R: Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol 2003;60:203–208.
  5. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JCS, for the Cache County Study Group: Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements. The Cache County Study. Arch Neurol 2004;61:82–88.
  6. Markesbery WR: The role of oxidative stress in Alzheimer disease. Arch Neurol 1999;56:1449–1452.
  7. Christen, Y: Oxidative stress and Alzheimer disease. Am J Clin Nutr 2000;71(suppl):621S–629S.
  8. Delanty N, Dichter MA: Antioxidant therapy in neurologic disease. Arch Neurol 2000;57:1265–1270.
  9. Misonou H, Morishima-Kawashima M, Ihara Y: Oxidative stress induces intracellular accumulation of amyloid β-protein (Aβ) in human neuroblastoma cells. Biochemistry 2000;39:6951–6959.
  10. Halliwell B: Role of free radicals in the neurodegenerative diseases. Therapeutic implications for antioxidant treatment. Drugs Aging 2001;18:685–716.
  11. Poon HF, Calabrese V, Scapagnini G, Butterfield DA: Free radicals: Key to brain aging and heme oxygenase as a cellular response to oxidative stress. J Gerontol A Biol Sci Med Sci 2004;59A:478–493.
  12. Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR: Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000;54:1265–1272.
  13. Morris MC, Beckett LA, Scherr PA, Hebert LE, Bennett DA, Field TS, Evans DA: Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord 1998;12:121–126.
  14. Morris MC, Evans DA, Bienias JL, Tangney CC, Wilson RS: Vitamin E and cognitive decline in older persons. Arch Neurol 2002;59:1125–1132.
  15. Teng EL, Chui HC: The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry 1987;48:314–318.
  16. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 3. Washington, American Psychiatric Association, 1987, pp 133–136.
  17. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984;34:939–944.
  18. World Health Organization: International Classification of Diseases, 10th revision: Clinical descriptions and diagnostic guidelines. Categories F00-F99, mental, behavioural and developmental disorders (1987 draft of chapter V). Geneva, World Health Organization, 1987, Rep No MNH/MEP/87.1 rev1.
  19. Canadian Study of Health and Aging Working Group: Canadian Study of Health and Aging: Study methods and prevalence of dementia. CMAJ 1994;150:899–913.
  20. The Canadian Study of Health and Aging Working Group: The incidence of dementia in Canada. Neurology 2000;55:66–73.
  21. Maxwell CJ, Hogan DB, Ebly EM: Serum folate levels and subsequent adverse cerebrovascular outcomes in elderly persons. Dement Geriatr Cogn Disord 2002;13:225–234.
  22. Maxwell CJ, Hogan DB, Ebly EM: Calcium-channel blockers and cognitive function in elderly people: Results from the Canadian Study of Health and Aging. CMAJ 1999;161:501–506.
  23. Rockwood K, Ebly E, Hachinski V, Hogan D: Presence and treatment of vascular risk factors in patients with vascular cognitive impairment. Arch Neurol 1997;54:33–39.
  24. Kelsey JL, Whittemore AS, Evans AS, Thompson WD: Methods in Observational Epidemiology, ed 2. New York, Oxford University Press, 1996.
  25. SAS Institute Inc: SAS User’s Guide, release 8.2 for Windows. Cary, SAS Institute Inc., 1999–2001.
  26. Tang M-X, Stern Y, Marder K, Bell K, Gurland B, Lantigua R, Andrews H, Feng L, Tycko B, Mayeux R: The APOE-ε4 allele and the risk of Alzheimer disease among African Americans, Whites and Hispanics. JAMA 1998;279:751–755.