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Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer’s disease: the National Finnish population study (FINRISK)

Abstract

Data on associations of apolipoproteins A-I and B (apo A-I, apo B) and HDL cholesterol (HDL-C) with dementia and Alzheimer’s disease (AD) are conflicting. Our aim was to examine, whether apo B, apoA-I, their ratio, or HDL-C are significant, independent predictors of incident dementia and AD in the general population free of dementia at baseline. We analyzed the results from two Finnish prospective population-based cohort studies in a total of 13,275 subjects aged 25 to 74 years with mainly Caucasian ethnicity. The follow-up time for both cohorts was 10 years. We used Cox proportional hazards regression to evaluate hazard ratios (HR) for incident dementia (including AD) (n = 220) and for AD (n = 154). Cumulative incidence function (CIF) analysis was also performed to adjust the results for competing risks of death. Adjusted for multiple dementia and AD risk factors, log-transformed apo A-I, log HDL-C, log apo B, and log apo B/A-I ratio were not associated with incident dementia or AD. HDL-C was inversely associated with AD risk when adjusted for competing risks but no other statistically significant associations were observed in the CIF analyses. Apo A-I, HDL-C, apo B, or apo B/A-I ratio were not associated with future dementia or AD. HDL-C was inversely associated with incident AD risk when adjusted for competing risks of death, but the finding is unlikely to be of clinical relevance. Our study does not support the use of these risk markers to predict incident dementia or AD.

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References

  • Allignol A, Schumacher M, Beyersmann J (2011) Empirical transition matrix of multi-state models: the etm package. J Stat Softw 38:1–15

    Article  Google Scholar 

  • Arntzen KA, Schirmer H, Wilsgaard T, Mathiesen EB (2011) Impact of cardiovascular risk factors on cognitive function: the Tromso study. Eur J Neurol 18:737–743. doi:10.1111/j.1468-1331.2010.03263.x

  • Buuren S, Groothuis-Oudshoorn K (2011) Mice: multivariate imputation by chained equations in R. J Stat Softw 45:1–67

    Article  Google Scholar 

  • Caramelli P, Nitrini R, Maranhao R, Lourenco AC, Damasceno MC, Vinagre C, Caramelli B (1999) Increased apolipoprotein B serum concentration in Alzheimer’s disease. Acta Neurol Scand 100:61–63

    CAS  Article  PubMed  Google Scholar 

  • Crisby M, Bronge L, Wahlund LO (2010) Low levels of high density lipoprotein increase the severity of cerebral white matter changes: implications for prevention and treatment of cerebrovascular diseases. Curr Alzheimer Res 7:534–539

    CAS  Article  PubMed  Google Scholar 

  • Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, Pennells L, Kaptoge S, Caslake M, Thompson A, Butterworth AS, Sarwar N, Wormser D et al (2012) Lipid-related markers and cardiovascular disease prediction. JAMA 307:2499–2506. doi:10.1001/jama.2012.6571

  • Gouw AA, van der Flier WM, Fazekas F, van Straaten EC, Pantoni L, Poggesi A, Inzitari D, Erkinjuntti T, Wahlund LO, Waldemar G et al (2008) Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study. Stroke 39:1414–1420. doi:10.1161/STROKEAHA.107.498535

  • Gray R (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16:1140–1154

    Article  Google Scholar 

  • Gray B (2014) cmprsk: Subdistribution Analysis of Competing Risks

  • Helbecque N, Codron V, Cottel D, Amouyel P (2008) An apolipoprotein A-I gene promoter polymorphism associated with cognitive decline, but not with Alzheimer’s disease. Dement Geriatr Cogn Disord 25:97–102. doi:10.1159/000112176

    CAS  Article  PubMed  Google Scholar 

  • Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM (2013) Monetary costs of dementia in the United States. N Engl J Med 368:1326–1334. doi:10.1056/NEJMsa1204629

  • Kaffashian S, Dugravot A, Elbaz A, Shipley MJ, Sabia S, Kivimaki M, Singh-Manoux A (2013) Predicting cognitive decline: a dementia risk score vs the Framingham vascular risk scores. Neurology 80:1300–1306. doi:10.1212/WNL.0b013e31828ab370

  • Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A (2001) Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ 322:1447–1451

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J (2006) Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 5:735–741. doi:10.1016/S1474-4422(06)70537-3

    Article  PubMed  Google Scholar 

  • Leiviska J, Sundvall J, Alfthan G, Tahtela R, Salomaa V, Jauhiainen M, Vartiainen E (2013) What have we learnt about high-density lipoprotein cholesterol measurements during 32 years? Experiences in Finland 1980-2012. Clin Chim Acta 415:118–123. doi:10.1016/j.cca.2012.10.027 [doi]

    CAS  Article  PubMed  Google Scholar 

  • Li G, Shofer JB, Kukull WA, Peskind ER, Tsuang DW, Breitner JC, McCormick W, Bowen JD, Teri L, Schellenberg GD et al (2005) Serum cholesterol and risk of Alzheimer disease: a community-based cohort study. Neurology 65:1045–1050. doi:10.1212/01.wnl.0000178989.87072.11

    CAS  Article  PubMed  Google Scholar 

  • Merched A, Xia Y, Visvikis S, Serot JM, Siest G (2000) Decreased high-density lipoprotein cholesterol and serum apolipoprotein AI concentrations are highly correlated with the severity of Alzheimer’s disease. Neurobiol Aging 21:27–30 doi: S0197-4580(99)00103-7 [pii]

    CAS  Article  PubMed  Google Scholar 

  • 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 64:1689–1695. doi:10.1212/01.WNL.0000161870.78572.A5

    CAS  Article  PubMed  Google Scholar 

  • Mura T, Dartigues JF, Berr C (2010) How many dementia cases in France and Europe? Alternative projections and scenarios 2010-2050. Eur J Neurol 17:252–259. doi:10.1111/j.1468-1331.2009.02783.x

    CAS  Article  PubMed  Google Scholar 

  • Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E (1988) Geographical variation in the major risk factors of coronary heart disease in men and women aged 35-64 years. The WHO MONICA Project. World Health Stat Q 41:115–140

    Google Scholar 

  • Pajunen P, Koukkunen H, Ketonen M, Jerkkola T, Immonen-Raiha P, Karja-Koskenkari P, Mahonen M, Niemela M, Kuulasmaa K, Palomaki P et al (2005) The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease. Eur J Cardiovasc Prev Rehabil 12:132–137 doi: 00149831-200504000-00007 [pii]

    PubMed  Google Scholar 

  • Paula-Lima AC, Tricerri MA, Brito-Moreira J, Bomfim TR, Oliveira FF, Magdesian MH, Grinberg LT, Panizzutti R, Ferreira ST (2009) Human apolipoprotein A-I binds amyloid-beta and prevents Abeta-induced neurotoxicity. Int J Biochem Cell Biol 41:1361–1370. doi:10.1016/j.biocel.2008.12.003 [doi]

    CAS  Article  PubMed  Google Scholar 

  • Qizilbash N, Gregson J, Johnson ME, Pearce N, Douglas I, Wing K, Evans SJ, Pocock SJ (2015) BMI and risk of dementia in two million people over two decades: a retrospective cohort study. Lancet Diabetes Endocrinol 3:431–436. doi:10.1016/S2213-8587(15)00033-9 [doi]

    Article  PubMed  Google Scholar 

  • Reitz C, Luchsinger J, Tang MX, Manly J, Mayeux R (2005) Impact of plasma lipids and time on memory performance in healthy elderly without dementia. Neurology 64:1378–1383. doi:10.1212/01.WNL.0000158274.31318.3C

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Reitz C, Tang MX, Schupf N, Manly JJ, Mayeux R, Luchsinger JA (2010) Association of higher levels of high-density lipoprotein cholesterol in elderly individuals and lower risk of late-onset Alzheimer disease. Arch Neurol 67:1491–1497. doi:10.1001/archneurol.2010.297

  • Reynolds CA, Gatz M, Prince JA, Berg S, Pedersen NL (2010) Serum lipid levels and cognitive change in late life. J Am Geriatr Soc 58:501–509. doi:10.1111/j.1532-5415.2010.02739.x

  • Rosolova H, Nussbaumerova B (2011) Cardio-metabolic risk prediction should be superior to cardiovascular risk assessment in primary prevention of cardiovascular diseases. EPMA J 2:15–26. doi:10.1007/s13167-011-0066-1 [doi]

    Article  PubMed  PubMed Central  Google Scholar 

  • Saczynski JS, White L, Peila RL, Rodriguez BL, Launer LJ (2007) The relation between apolipoprotein A-I and dementia: the Honolulu-Asia aging study. Am J Epidemiol 165:985–992. doi:10.1093/aje/kwm027

    Article  PubMed  Google Scholar 

  • Schwarzer G (2015) meta: General Package for Meta-Analysis

  • Shibata N, Nagata T, Shinagawa S, Ohnuma T, Shimazaki H, Komatsu M, Kuerban B, Tomson K, Nakayama K, Yamada H et al (2013) Genetic association between APOA1 and APOD polymorphisms and Alzheimer’s disease in a Japanese population. J Neural Transm 120:1599–1603. doi:10.1007/s00702-013-1036-7 [doi]

    CAS  Article  PubMed  Google Scholar 

  • Smach MA, Edziri H, Charfeddine B, Ben Othman L, Lammouchi T, Ltaief A, Nafati S, Dridi H, Bennamou S, Limem K (2011) Polymorphism in apoA1 influences high-density lipoprotein cholesterol levels but is not a major risk factor of Alzheimer’s disease. Dement Geriatr Cogn Dis Extra 1:249–257. doi:10.1159/000329910

  • 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 68:751–756. doi:10.1212/01.wnl.0000256368.57375.b7

    CAS  Article  PubMed  Google Scholar 

  • Solomon A, Ngandu T, Soininen H, Hallikainen MM, Kivipelto M, Laatikainen T (2013) Validity of dementia and Alzheimer disease diagnoses in Finnish national registers. Alzheimers Dement. doi:10.1016/j.jalz.2013.03.004

  • Sundvall J, Leiviska J, Alfthan G, Vartiainen E (2007) Serum cholesterol during 27 years: assessment of systematic error and affecting factors and their role in interpreting population trends. Clin Chim Acta 378:93–98 doi: S0009-8981(06)00710-8 [pii]

    CAS  Article  PubMed  Google Scholar 

  • Team RC (2013) R: A Language and Environment for Statistical Computing

  • Therneau TM (2014) A Package for Survival Analysis in S

  • Tingley D, Yamamoto T, Hirose K, Keele L, Imai K (2014) Mediation: R Package for Causal Mediation Analysis. J Stat Softw 59:1–38

    Article  Google Scholar 

  • Tynkkynen J, Laatikainen T, Salomaa V, Havulinna AS, Blankenberg S, Zeller T, Hernesniemi JA (2015) NT-proBNP and the risk of dementia: a prospective cohort study with 14 years of follow-up. J Alzheimers Dis 44:1007–1013. doi:10.3233/JAD-141809

    CAS  PubMed  Google Scholar 

  • Vartiainen E, Laatikainen T, Peltonen M, Juolevi A, Mannisto S, Sundvall J, Jousilahti P, Salomaa V, Valsta L, Puska P (2010) Thirty-five-year trends in cardiovascular risk factors in Finland. Int J Epidemiol 39:504–518. doi:10.1093/ije/dyp330

  • Vollbach H, Heun R, Morris CM, Edwardson JA, McKeith IG, Jessen F, Schulz A, Maier W, Kolsch H (2005) APOA1 polymorphism influences risk for early-onset nonfamiliar AD. Ann Neurol 58:436–441. doi:10.1002/ana.20593

    CAS  Article  PubMed  Google Scholar 

  • Whitmer RA, Gunderson EP, Quesenberry CP Jr, Zhou J, Yaffe K (2007) Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr Alzheimer Res 4:103–109

    CAS  Article  PubMed  Google Scholar 

  • Yin ZG, Li L, Cui M, Zhou SM, Yu MM, Zhou HD (2014) Inverse relationship between apolipoprotein A-I and cerebral white matter lesions: a cross-sectional study in middle-aged and elderly subjects. PLoS One 9:e97113. doi:10.1371/journal.pone.0097113

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Salomaa V. was supported by the Finnish Foundation for Cardiovascular Research. Tynkkynen J. was supported by the University of Eastern Finland to conduct this paper as part of his doctoral thesis. None of the funders had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

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Correspondence to Juho Tynkkynen.

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Tynkkynen, J., Hernesniemi, J.A., Laatikainen, T. et al. Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer’s disease: the National Finnish population study (FINRISK). AGE 38, 465–473 (2016). https://doi.org/10.1007/s11357-016-9950-x

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  • DOI: https://doi.org/10.1007/s11357-016-9950-x

Keywords

  • Apolipoprotein A-I
  • Apolipoprotein B
  • HDL-C
  • Dementia
  • Alzheimer’s disease
  • Prospective
  • ApoE genotype