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Vol. 28, No. 1, 2009
Issue release date: August 2009
Section title: Original Research Article
Free Access
Dement Geriatr Cogn Disord 2009;28:75–80
(DOI:10.1159/000231980)

Midlife Serum Cholesterol and Increased Risk of Alzheimer’s and Vascular Dementia Three Decades Later

Solomon A.a, b · Kivipelto M.a, b · Wolozin B.c · Zhou J.d · Whitmer R.A.d
aDepartment of Neurology, University of Kuopio, Kuopio, Finland; bAging Research Center, Karolinska Institutet, Stockholm, Sweden; cDepartment of Pharmacology, Boston University School of Medicine, Boston, Mass., and dDivision of Research, Kaiser Permanente, Oakland, Calif., USA
email Corresponding Author

Abstract

Aims: To investigate midlife cholesterol in relation to Alzheimer’s disease (AD) and vascular dementia (VaD) in a large multiethnic cohort of women and men. Methods: The Kaiser Permanente Northern California Medical Group (healthcare delivery organization) formed the database for this study. The 9,844 participants underwent detailed health evaluations during 1964–1973 at ages 40–45 years; they were still members of the health plan in 1994. AD and VaD were ascertained by medical records between 1 January 1994 and 1 June 2007. Cox proportional hazards models – adjusted for age, education, race/ethnic group, sex, midlife diabetes, hypertension, BMI and late-life stroke – were conducted. Results: In total, 469 participants had AD and 127 had VaD. With desirable cholesterol levels (<200 mg/dl) as a reference, hazard ratios (HR) and 95% CI for AD were 1.23 (0.97–1.55) and 1.57 (1.23–2.01) for borderline (200–239 mg/dl) and high cholesterol (≥240 mg/dl), respectively. HR and 95% CI for VaD were 1.50 (1.01–2.23) for borderline and 1.26 (0.82–1.96) for high cholesterol. Further analyses for AD (cholesterol quartiles, 1st quartile reference) indicated that cholesterol levels >220 mg/dl were a significant risk factor: HR were 1.31 (1.01–1.71; 3rd quartile, 221–248 mg/dl) and 1.58 (1.22–2.06; 4th quartile, 249–500 mg/dl). Conclusion: Midlife serum total cholesterol was associated with an increased risk of AD and VaD. Even moderately elevated cholesterol increased dementia risk. Dementia risk factors need to be addressed as early as midlife, before underlying disease(s) or symptoms appear.

© 2009 S. Karger AG, Basel


  

Key Words

  • Dementia
  • Epidemiology
  • Alzheimer’s dementia
  • Cholesterol
  • Vascular dementia

References

  1. Hachinski V: Stroke and vascular cognitive impairment: a transdisciplinary, translational and transactional approach. Stroke 2007;38:1396–1403.
  2. Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J: Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 2006;5:735–741.
  3. Aguero-Torres H, Kivipelto M, von Strauss E: Rethinking the dementia diagnoses in a population-based study: what is Alzheimer’s disease and what is vascular dementia? A study from the Kungsholmen project. Dement Geriatr Cogn Disord 2006;22:244–249.
  4. Rockwood K: Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer’s disease. Acta Neurol Scand Suppl 2006;185:71–77.
  5. He K, Xu Y, van Horn L: The puzzle of dietary fat intake and risk of ischemic stroke: a brief review of epidemiologic data. J Am Diet Assoc 2007;107:287–295.
  6. Romero JR: Prevention of ischemic stroke: overview of traditional risk factors. Curr Drug Targets 2007;8:794–801.
  7. Hachinski V, Iadecola C, Petersen RC, et al: National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220–2241.
  8. Bjorkhem I: Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 2006;260:493–508.
  9. Stewart R, White LR, Xue QL, Launer LJ: Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia Aging Study. Arch Neurol 2007;64:103–107.
  10. Solomon A, Kåreholt I, Ngandu T, et al: Serum cholesterol changes after midlife and late-life cognition: 21-year follow-up study. Neurology 2007;68:751–756.
  11. National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Final Report (NIH Publication No. 02-5215). Bethesda, National Heart, Lung and Blood Institute, National Institutes of Health, 2002.
  12. Arellano MG, Petersen GR, Petitti DB, Smith RE: The California Automated Mortality Linkage System (CAMLIS). Am J Public Health 1984;74:1324–1330.
  13. Iribarren C, Sidney S, Sternfeld B, Browner WS: Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. JAMA 2000;283:2810–2815.
  14. Collen MF, Davis LF: The multitest laboratory in health care. J Occup Med 1969;11:355–360.
  15. Collen MF: Multiphasic Health Testing Services. New York, John Wiley & Sons, 1978.
  16. Krieger N: Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health 1992;82:703–710.
  17. Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K: Midlife cardiovascular risk factors and risk of dementia in late-life. Neurology 2005;64:277–281.
  18. Tan ZS, Seshadri S, Beiser A, et al: Plasma total cholesterol level as a risk factor for Alzheimer disease: the Framingham Study. Arch Intern Med 2003;163:1053–1057.
  19. Kalmijn S, Foley D, White L, et al: Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men: the Honolulu-Asia aging study. Arterioscler Thromb Vasc Biol 2000;20:2255–2260.
  20. Kivipelto M, Helkala EL, Laakso MP, et al: Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002;137:149–155.
  21. Notkola IL, Sulkava R, Pekkanen J, et al: Serum total cholesterol, apolipoprotein E ε4 allele, and Alzheimer’s disease. Neuroepidemiology 1998;17:14–20.
  22. Kivipelto M, Solomon A: Cholesterol as a risk factor for Alzheimer’s disease – epidemiological evidence. Acta Neurol Scand Suppl 2006;185:50–57.

  

Author Contacts

Alina Solomon
Department of Neurology, University of Kuopio
PO Box 1627
FI–70211 Kuopio (Finland)
Tel. +46 8 690 5822, Fax +46 8 690 5954, E-Mail alina.solomon@uku.fi

  

Article Information

Accepted: April 27, 2009
Published online: August 4, 2009
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 4, Number of References : 22

  

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 28, No. 1, Year 2009 (Cover Date: August 2009)

Journal Editor: Chan-Palay V. (New York, N.Y.)
ISSN: 1420-8008 (Print), eISSN: 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

Aims: To investigate midlife cholesterol in relation to Alzheimer’s disease (AD) and vascular dementia (VaD) in a large multiethnic cohort of women and men. Methods: The Kaiser Permanente Northern California Medical Group (healthcare delivery organization) formed the database for this study. The 9,844 participants underwent detailed health evaluations during 1964–1973 at ages 40–45 years; they were still members of the health plan in 1994. AD and VaD were ascertained by medical records between 1 January 1994 and 1 June 2007. Cox proportional hazards models – adjusted for age, education, race/ethnic group, sex, midlife diabetes, hypertension, BMI and late-life stroke – were conducted. Results: In total, 469 participants had AD and 127 had VaD. With desirable cholesterol levels (<200 mg/dl) as a reference, hazard ratios (HR) and 95% CI for AD were 1.23 (0.97–1.55) and 1.57 (1.23–2.01) for borderline (200–239 mg/dl) and high cholesterol (≥240 mg/dl), respectively. HR and 95% CI for VaD were 1.50 (1.01–2.23) for borderline and 1.26 (0.82–1.96) for high cholesterol. Further analyses for AD (cholesterol quartiles, 1st quartile reference) indicated that cholesterol levels >220 mg/dl were a significant risk factor: HR were 1.31 (1.01–1.71; 3rd quartile, 221–248 mg/dl) and 1.58 (1.22–2.06; 4th quartile, 249–500 mg/dl). Conclusion: Midlife serum total cholesterol was associated with an increased risk of AD and VaD. Even moderately elevated cholesterol increased dementia risk. Dementia risk factors need to be addressed as early as midlife, before underlying disease(s) or symptoms appear.

© 2009 S. Karger AG, Basel


  

Author Contacts

Alina Solomon
Department of Neurology, University of Kuopio
PO Box 1627
FI–70211 Kuopio (Finland)
Tel. +46 8 690 5822, Fax +46 8 690 5954, E-Mail alina.solomon@uku.fi

  

Article Information

Accepted: April 27, 2009
Published online: August 4, 2009
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 4, Number of References : 22

  

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 28, No. 1, Year 2009 (Cover Date: August 2009)

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

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


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Accepted: 4/27/2009
Published online: 8/4/2009
Issue release date: August 2009

Number of Print Pages: 6
Number of Figures: 0
Number of Tables: 4

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. Hachinski V: Stroke and vascular cognitive impairment: a transdisciplinary, translational and transactional approach. Stroke 2007;38:1396–1403.
  2. Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J: Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 2006;5:735–741.
  3. Aguero-Torres H, Kivipelto M, von Strauss E: Rethinking the dementia diagnoses in a population-based study: what is Alzheimer’s disease and what is vascular dementia? A study from the Kungsholmen project. Dement Geriatr Cogn Disord 2006;22:244–249.
  4. Rockwood K: Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer’s disease. Acta Neurol Scand Suppl 2006;185:71–77.
  5. He K, Xu Y, van Horn L: The puzzle of dietary fat intake and risk of ischemic stroke: a brief review of epidemiologic data. J Am Diet Assoc 2007;107:287–295.
  6. Romero JR: Prevention of ischemic stroke: overview of traditional risk factors. Curr Drug Targets 2007;8:794–801.
  7. Hachinski V, Iadecola C, Petersen RC, et al: National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220–2241.
  8. Bjorkhem I: Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 2006;260:493–508.
  9. Stewart R, White LR, Xue QL, Launer LJ: Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia Aging Study. Arch Neurol 2007;64:103–107.
  10. Solomon A, Kåreholt I, Ngandu T, et al: Serum cholesterol changes after midlife and late-life cognition: 21-year follow-up study. Neurology 2007;68:751–756.
  11. National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Final Report (NIH Publication No. 02-5215). Bethesda, National Heart, Lung and Blood Institute, National Institutes of Health, 2002.
  12. Arellano MG, Petersen GR, Petitti DB, Smith RE: The California Automated Mortality Linkage System (CAMLIS). Am J Public Health 1984;74:1324–1330.
  13. Iribarren C, Sidney S, Sternfeld B, Browner WS: Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. JAMA 2000;283:2810–2815.
  14. Collen MF, Davis LF: The multitest laboratory in health care. J Occup Med 1969;11:355–360.
  15. Collen MF: Multiphasic Health Testing Services. New York, John Wiley & Sons, 1978.
  16. Krieger N: Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health 1992;82:703–710.
  17. Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K: Midlife cardiovascular risk factors and risk of dementia in late-life. Neurology 2005;64:277–281.
  18. Tan ZS, Seshadri S, Beiser A, et al: Plasma total cholesterol level as a risk factor for Alzheimer disease: the Framingham Study. Arch Intern Med 2003;163:1053–1057.
  19. Kalmijn S, Foley D, White L, et al: Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men: the Honolulu-Asia aging study. Arterioscler Thromb Vasc Biol 2000;20:2255–2260.
  20. Kivipelto M, Helkala EL, Laakso MP, et al: Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002;137:149–155.
  21. Notkola IL, Sulkava R, Pekkanen J, et al: Serum total cholesterol, apolipoprotein E ε4 allele, and Alzheimer’s disease. Neuroepidemiology 1998;17:14–20.
  22. Kivipelto M, Solomon A: Cholesterol as a risk factor for Alzheimer’s disease – epidemiological evidence. Acta Neurol Scand Suppl 2006;185:50–57.