Skip to main content

Advertisement

SpringerLink
Log in

Cholesterol in mild cognitive impairment and Alzheimer’s disease in a birth cohort over 14 years

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Animal epidemiological and clinical studies suggest that cholesterol is a risk factor for Alzheimer’s disease (AD). Nevertheless, the relation of cholesterol to mild cognitive impairment (MCI), influence of APOE genotype and its changes in lifespan is controversial. We investigated the potential impact of plasma total cholesterol (TC) on development of MCI and AD in the interdisciplinary longitudinal study on adult development and aging, a representative birth cohort (born 1930–1932), examined in 1993/1994 (VT1), 1997/1998 (VT2), and 2005/2007 (VT3). Of 500 participants at baseline, 381 survived and were examined at VT3. After exclusion of participants with lifetime prevalence of major psychiatric diseases or mild cognitive disorder due to a medical condition, 222 participants were included in the analysis. At VT3, 82 participants had MCI, 22 participants had AD, and 118 were in good health. Participants with MCI and AD at VT3 evidenced higher TC levels at VT1 than those who were healthy. Higher TC levels at baseline were associated with an increased risk for cognitive disorders at VT3 (highest vs. lowest quartile: OR 2.64, 95 % CI 1.12–6.23, p < 0.05). Over the 14 year follow-up, TC levels declined in those with MCI and AD, but remained stable in those who remained healthy. These findings were not modified by APOE genotype or use of cholesterol-lowering medications. Our findings demonstrate that higher TC levels are observed long before the clinical manifestation of MCI and AD in patients without psychiatric or somatic comorbidities and are independent of APOE genotype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schonknecht P, Lutjohann D, Pantel J, Bardenheuer H, Hartmann T, von Bergmann K, Beyreuther K, Schroder J (2002) Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with Alzheimer’s disease compared to healthy controls. Neurosci Lett 324(1):83–85

    Article  CAS  PubMed  Google Scholar 

  2. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Iivonen S, Mannermaa A, Tuomilehto J, Nissinen A, Soininen H (2002) 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 137(3):149–155

    Article  CAS  PubMed  Google Scholar 

  3. Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K (2005) Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 64(2):277–281. doi:10.1212/01.WNL.0000149519.47454.F2

    Article  CAS  PubMed  Google Scholar 

  4. Solomon A, Kareholt I, Ngandu T, Winblad B, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M (2007) Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study. Neurology 68(10):751–756. doi:10.1212/01.wnl.0000256368.57375.b7

    Article  CAS  PubMed  Google Scholar 

  5. Kivipelto M, Solomon A (2006) Cholesterol as a risk factor for Alzheimer’s disease—epidemiological evidence. Acta Neurol Scand Suppl 185:50–57. doi:10.1111/j.1600-0404.2006.00685.x

    Article  Google Scholar 

  6. Anstey KJ, Lipnicki DM, Low LF (2008) Cholesterol as a risk factor for dementia and cognitive decline: a systematic review of prospective studies with meta-analysis. Am J Geriatr Psychiatry 16(5):343–354. doi:10.1097/JGP.0b013e31816b72d4

    Article  PubMed  Google Scholar 

  7. Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE (2007) Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med 5:20. doi:10.1186/1741-7015-5-20

    Article  PubMed Central  PubMed  Google Scholar 

  8. Li G, Larson EB, Sonnen JA, Shofer JB, Petrie EC, Schantz A, Peskind ER, Raskind MA, Breitner JC, Montine TJ (2007) Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology 69(9):878–885. doi:10.1212/01.wnl.0000277657.95487.1c

    Article  CAS  PubMed  Google Scholar 

  9. Mielke MM, Zandi PP, Shao H, Waern M, Ostling S, Guo X, Bjorkelund C, Lissner L, Skoog I, Gustafson DR (2010) The 32-year relationship between cholesterol and dementia from midlife to late life. Neurology 75(21):1888–1895. doi:10.1212/WNL.0b013e3181feb2bf

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Stewart R, White LR, Xue QL, Launer LJ (2007) Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia Aging Study. Arch Neurol 64(1):103–107. doi:10.1001/archneur.64.1.103

    Article  PubMed  Google Scholar 

  11. Tokuda T, Calero M, Matsubara E, Vidal R, Kumar A, Permanne B, Zlokovic B, Smith JD, Ladu MJ, Rostagno A, Frangione B, Ghiso J (2000) Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer’s amyloid beta peptides. Biochem J 348(Pt 2):359–365

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Howland DS, Trusko SP, Savage MJ, Reaume AG, Lang DM, Hirsch JD, Maeda N, Siman R, Greenberg BD, Scott RW, Flood DG (1998) Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol. J Biol Chem 273(26):16576–16582

    Article  CAS  PubMed  Google Scholar 

  13. Schroder J, Kratz B, Pantel J, Minnemann E, Lehr U, Sauer H (1998) Prevalence of mild cognitive impairment in an elderly community sample. J Neural Transm Suppl 54:51–59

    Article  Google Scholar 

  14. Schonknecht P, Pantel J, Kruse A, Schroder J (2005) Prevalence and natural course of aging-associated cognitive decline in a population-based sample of young-old subjects. Am J Psychiatry 162(11):2071–2077

    Article  PubMed  Google Scholar 

  15. Martin P, Martin M (2000) Design und Methodik der Interdisziplinären Längsschnittstudie des Erwachsenenalters. In: Martin P (ed) Aspekte der Entwicklung im mittleren und höheren Erwachsenenalter. Steinkopff, Darmstadt, pp 17–27

    Chapter  Google Scholar 

  16. Wittchen H, Zaudig M, Schramm E, Spengler P, Mombour W, Klug J, Horn R (1991) Strukturiertes klinisches Interview für DSM-III-R. Beltz-Test, Göttingen

    Google Scholar 

  17. Levy R (1994) Aging-associated cognitive decline. Working party of the International Psychogeriatric Association in collaboration with the World Health Organization. Int Psychogeriatr 6(1):63–68

    Article  CAS  PubMed  Google Scholar 

  18. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) 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 34(7):939–944

    Article  CAS  PubMed  Google Scholar 

  19. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS–AIREN international workshop. Neurology 43(2):250–260

    Article  CAS  PubMed  Google Scholar 

  20. Aslanidis C, Schmitz G (1999) High-speed apolipoprotein E genotyping and apolipoprotein B3500 mutation detection using real-time fluorescence PCR and melting curves. Clin Chem 45(7):1094–1097

    CAS  PubMed  Google Scholar 

  21. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198

    Article  CAS  PubMed  Google Scholar 

  22. Oswald W, Fleischmann V (1991) Nürnberger Alters–Inventar. Universität Erlangen-Nürnberg, Erlangen

    Google Scholar 

  23. Sturm W, Willmes K, Horn W (1993) Leistungsprüfsystem für 50-90jährige. Hogrefe, Göttingen

    Google Scholar 

  24. Brickenkamp R (1978) Test d2: Aufmerksamkeits–Belastungs-test. Hofgrefe, Göttingen

    Google Scholar 

  25. Tewes W (1991) HAWIE-R: Hamburg–Wchsler–Intelligneztest für Erwachsene, revision. Huber, Bern

    Google Scholar 

  26. Mielke MM, Zandi PP, Sjogren M, Gustafson D, Ostling S, Steen B, Skoog I (2005) High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology 64(10):1689–1695. doi:10.1212/01.WNL.0000161870.78572.A5

    Article  CAS  PubMed  Google Scholar 

  27. Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissinen A (2005) Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 62(10):1556–1560. doi:10.1001/archneur.62.10.1556

    Article  PubMed  Google Scholar 

  28. Notkola IL, Sulkava R, Pekkanen J, Erkinjuntti T, Ehnholm C, Kivinen P, Tuomilehto J, Nissinen A (1998) Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer’s disease. Neuroepidemiology 17(1):14–20

    Article  CAS  PubMed  Google Scholar 

  29. Reitz C, Tang MX, Luchsinger J, Mayeux R (2004) Relation of plasma lipids to Alzheimer disease and vascular dementia. Arch Neurol 61(5):705–714. doi:10.1001/archneur.61.5.70561/5/705

    Article  PubMed Central  PubMed  Google Scholar 

  30. Coffey CE, Saxton JA, Ratcliff G, Bryan RN, Lucke JF (1999) Relation of education to brain size in normal aging: implications for the reserve hypothesis. Neurology 53(1):189–196

    Article  CAS  PubMed  Google Scholar 

  31. Richter V, Rassoul F, Hentschel B, Kothe K, Krobara M, Unger R, Purschwitz K, Rotzsch W, Thiery J, Muradian K (2004) Age-dependence of lipid parameters in the general population and vegetarians. Z Gerontol Geriatr 37(3):207–213. doi:10.1007/s00391-004-0232-3

    Article  CAS  PubMed  Google Scholar 

  32. Mielke M, Zandi P, Shao H, Waern M, Östling S, Guo X, Björkelund C, Lissner L, Skoog I, Gustafson D (2010) The 32 year relationship between cholesterol and dementia from mid- to late-life. Neurology 75(21):1888–1895

    Google Scholar 

  33. Gustafson DR, Melchior L, Eriksson E, Sundh V, Blennow K, Skoog I (2010) The ACE insertion deletion polymorphism relates to dementia by metabolic phenotype, APOEepsilon4, and age of dementia onset. Neurobiol Aging 31(6):910–916. doi:10.1016/j.neurobiolaging.2008.07.015

    Article  CAS  PubMed  Google Scholar 

  34. Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L, Cohen D (1994) Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 6(1):29–32. doi:10.1038/ng0194-29

    Article  CAS  PubMed  Google Scholar 

  35. Tang MX, Stern Y, Marder K, Bell K, Gurland B, Lantigua R, Andrews H, Feng L, Tycko B, Mayeux R (1998) The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA 279(10):751–755

    Article  CAS  PubMed  Google Scholar 

  36. Hall K, Murrell J, Ogunniyi A, Deeg M, Baiyewu O, Gao S, Gureje O, Dickens J, Evans R, Smith-Gamble V, Unverzagt FW, Shen J, Hendrie H (2006) Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba. Neurology 66(2):223–227. doi:10.1212/01.wnl.0000194507.39504.17

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Mahley RW, Rall SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1:507–537. doi:10.1146/annurev.genom.1.1.507

    Article  CAS  PubMed  Google Scholar 

  38. Sing CF, Davignon J (1985) Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 37(2):268–285

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Wehr H, Parnowski T, Puzynski S, Bednarska-Makaruk M, Bisko M, Kotapka-Minc S, Rodo M, Wolkowska M (2000) Apolipoprotein E genotype and lipid and lipoprotein levels in dementia. Dement Geriatr Cogn Disord 11(2):70–73

    Article  CAS  PubMed  Google Scholar 

  40. Cramer C, Haan MN, Galea S, Langa KM, Kalbfleisch JD (2008) Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 71(5):344–350. doi:10.1212/01.wnl.0000319647.15752.7b

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Rockwood K (2006) Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer’s disease. Acta Neurol Scand 185:71–77. doi:10.1111/j.1600-0404.2006.00688.x

    Article  CAS  Google Scholar 

  42. Beydoun MA, Beason-Held LL, Kitner-Triolo MH, Beydoun HA, Ferrucci L, Resnick SM, Zonderman AB (2011) Statins and serum cholesterol’s associations with incident dementia and mild cognitive impairment. J Epidemiol Community Health 65(11):949–957. doi:10.1136/jech.2009.100826

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The interdisciplinary longitudinal study on adult development and aging (ILSE) was supported by the “Research Program of the State of Baden-Württemberg” and the “Federal Ministry for Family, Senior Citizen, Women, and Youth, Germany.” P. Toro and J. Schröder received additional support by the “Marsilius Kolleg,” center of advanced studies, University of Heidelberg, Germany. This work was supported by the European Commission under the 7th Framework Programme of the European Union “Therapeutic and preventive impact of nutritional lipids on neuronal and cognitive performance in aging, Alzheimer’s disease and vascular dementia” coordinated by Prof Dr. Tobias Hartmann.

Conflict of interest

P. Toro, CH. Degen, D. Gustafson, M.Pierer, P. Schönknecht and J. Schröder declare no conflict of interest.

Author information

Authors and Affiliations

  1. Section of Geriatric Psychiatry, University of Heidelberg, Voss Strasse 4, 69115, Heidelberg, Germany

    P. Toro, Ch. Degen, J. Schröder & P. Schönknecht

  2. Department of Psychiatry, Faculty of Medicine, Catholic University of Chile, Marcoleta 381 Dpto 21, Santiago, Chile

    P. Toro

  3. Department of Internal Medicine, University of Leipzig, Liebigstr. 27, 04103, Leipzig, Germany

    M. Pierer

  4. Section for Psychiatry and Neurochemistry, Neuropsychiatric Epidemiology Unit, Sahlgrenska Academy, Gothenburg University, Göteborg, Sweden

    D. Gustafson

  5. Departments of Neurology and Medicine, SUNY-Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY, 11203, USA

    D. Gustafson

  6. Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103, Leipzig, Germany

    P. Schönknecht

Authors
  1. P. Toro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ch. Degen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Pierer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Gustafson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Schröder
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Schönknecht
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Toro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Toro, P., Degen, C., Pierer, M. et al. Cholesterol in mild cognitive impairment and Alzheimer’s disease in a birth cohort over 14 years. Eur Arch Psychiatry Clin Neurosci 264, 485–492 (2014). https://doi.org/10.1007/s00406-013-0468-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-013-0468-2

Keywords

Search

Navigation