Advertisement

European Journal of Epidemiology

, Volume 28, Issue 5, pp 405–416 | Cite as

Midlife cardiovascular risk factors and late cognitive impairment

  • Jyri J. Virta
  • Kauko Heikkilä
  • Markus Perola
  • Markku Koskenvuo
  • Ismo Räihä
  • Juha O. Rinne
  • Jaakko Kaprio
NEURO-EPIDEMIOLOGY

Abstract

Cardiovascular risk factors increase the risk of dementia in later life. The aims of the current study were to assess the effect of multiple midlife cardiovascular risk factors on the risk of cognitive impairment in later life, and to assess the validity of the previously suggested CAIDE Study risk score predicting dementia risk 20 years later. A total of 2,165 Finnish twins were followed and at the end of the follow-up their cognitive status was assessed with a validated telephone interview. The assessment of the risk factors at baseline was based on a self-report questionnaire. Relative risk ratios (RR) were calculated and receiver operating characteristic analyses performed. Midlife obesity (RR 2.42, 95 % CI 1.47–3.98), hypertension (RR 1.38, 95 % CI 1.01–1.88) and low leisure time physical activity (RR 2.52, 95 % CI 1.10–5.76) increased the risk of cognitive impairment after a mean follow-up of 22.6 ± 2.3 years. Hypercholesterolemia did not significantly increase the risk (RR 1.52, 95 % CI 0.92–2.51). Overweight individuals who gained more than 10 % weight between 1981 and 1990 had an increased risk of cognitive impairment (RR 4.27, 95 % CI 1.62–11.2). The CAIDE Study risk score combining various individual risk factors had an area-under-curve of 0.74 (95 % CI 0.69–0.79, n = 591), and there was a strong association between an increasing risk score and the risk of cognitive impairment. The results indicate that multiple midlife cardiovascular risk factors increase the risk of cognitive impairment in later life. Also, a risk score including easily measurable midlife factors predicts an individual’s cognitive impairment risk well.

Keywords

All cognitive disorders/dementia Alzheimer’s disease Risk factors in epidemiology Cohort studies 

Abbreviations

AD

Alzheimer’s disease

CAIDE

Finnish Cardiovascular Risk Factors, Aging and Dementia study

MZ

Monozygotic

DZ

Dizygotic

MICF

Mild impairment in cognitive function

BMI

Body mass index

MET

Metabolic equivalent

ApoE

Apolipoprotein E

RR

Relative risk ratio

95 % CI

95 % confidence interval

EPV

Events per variable

ROC

Receiver operating characteristic

AUC

Area-under-curve

OR

Odds ratio

Notes

Acknowledgments

The skilful assistance of research nurses Ulla Kulmala-Gråhn, Maarit Mantere and Kristiina Saanakorpi in interviewing the subjects is gratefully acknowledged. The assistance of Maarit Lappalainen at FIMM with ApoE genotyping is acknowledged. This study was financially supported by the Academy of Finland (project #205954), the Sigrid Juselius Foundation and Clinical grants of Turku University Hospital (EVO). The Finnish Twin Cohort study is part of the Academy of Finland Center of Excellence in Complex Disease Genetics (grant #s 213506, 129680).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature. 2009;461:916–22.CrossRefPubMedGoogle Scholar
  2. 2.
    Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology. 2005;64:277–81.CrossRefPubMedGoogle Scholar
  3. 3.
    Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, et al. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000;21:49–55.CrossRefPubMedGoogle Scholar
  4. 4.
    Kivipelto M, Helkala E, Laakso M, Hänninen T, Hallikainen M, Alhainen K, et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ (Clinical Research Ed). 2001;322:1447–51.CrossRefGoogle Scholar
  5. 5.
    Kalmijn S, Foley D, White L, Burchfiel CM, Curb JD, Petrovitch H, et al. Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia aging study. Arterioscler Thromb Vasc Biol. 2000;20:2255–60.CrossRefPubMedGoogle Scholar
  6. 6.
    Peila R, White LR, Petrovich H, Masaki K, Ross GW, Havlik RJ, et al. Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment: the Honolulu-Asia aging study. Stroke. 2001;32:2882–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Notkola IL, Sulkava R, Pekkanen J, Erkinjuntti T, Ehnholm C, Kivinen P, et al. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer’s disease. Neuroepidemiology. 1998;17:14–20.CrossRefPubMedGoogle Scholar
  8. 8.
    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;64:103–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Solomon A, Kareholt I, Ngandu T, Winblad B, Nissinen A, Tuomilehto J, et al. Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study. Neurology. 2007;68:751–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Anstey KJ, Cherbuin N, Budge M, Young J. Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev. 2011;12:e426–37.CrossRefPubMedGoogle Scholar
  11. 11.
    Rovio S, Kareholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol. 2005;4:705–11.CrossRefPubMedGoogle Scholar
  12. 12.
    Andel R, Crowe M, Pedersen NL, Fratiglioni L, Johansson B, Gatz M. Physical exercise at midlife and risk of dementia three decades later: a population-based study of Swedish twins. J Gerontol A Biol Sci Med Sci. 2008;63:62–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Yamada M, Kasagi F, Sasaki H, Masunari N, Mimori Y, Suzuki G. Association between dementia and midlife risk factors: the radiation effects research foundation adult health study. J Am Geriatr Soc. 2003;51:410–4.CrossRefPubMedGoogle Scholar
  14. 14.
    Rovio S, Kareholt I, Viitanen M, Winblad B, Tuomilehto J, Soininen H, et al. Work-related physical activity and the risk of dementia and Alzheimer’s disease. Int J Geriatr Psychiatry. 2007;22:874–82.CrossRefPubMedGoogle Scholar
  15. 15.
    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;5:735–41.CrossRefPubMedGoogle Scholar
  16. 16.
    Kaprio J, Sarna S, Koskenvuo M, Rantasalo I. The Finnish Twin Registry: formation and compilation, questionnaire study, zygosity determination procedures, and research program. Prog Clin Biol Res. 1978;24(Pt B):179–84.PubMedGoogle Scholar
  17. 17.
    Kaprio J, Koskenvuo M. Genetic and environmental factors in complex diseases: the older Finnish Twin Cohort. Twin Res. 2002;5:358–65.PubMedGoogle Scholar
  18. 18.
    Gatz M, Reynolds C, Nikolic J, Lowe B, Karel M, Pedersen N. An empirical test of telephone screening to identify potential dementia cases. Int Psychogeriatr. 1995;7:429–38.CrossRefPubMedGoogle Scholar
  19. 19.
    Järvenpää T, Rinne JO, Räihä I, Koskenvuo M, Löppönen M, Hinkka S, et al. Characteristics of two telephone screens for cognitive impairment. Dement Geriatr Cogn Disord. 2002;13:149–55.CrossRefPubMedGoogle Scholar
  20. 20.
    Järvenpää T, Rinne JO, Koskenvuo M, Räihä I, Kaprio J. Binge drinking in midlife and dementia risk. Epidemiology (Cambridge, Mass). 2005;16:766–71.CrossRefGoogle Scholar
  21. 21.
    Gatz M, Reynolds CA, John R, Johansson B, Mortimer JA, Pedersen NL. Telephone screening to identify potential dementia cases in a population-based sample of older adults. Int Psychogeriatr. 2002;14:273–89.CrossRefPubMedGoogle Scholar
  22. 22.
    World Health Organization. Global Database on Body Mass Index: BMI classification. 2011;2011.Google Scholar
  23. 23.
    Korkeila M, Kaprio J, Rissanen A, Koshenvuo M, Sorensen TI. Predictors of major weight gain in adult Finns: stress, life satisfaction and personality traits. Int J Obes Relat Metab Disord. 1998;22:949–57.CrossRefPubMedGoogle Scholar
  24. 24.
    Haapanen N, Miilunpalo S, Pasanen M, Oja P, Vuori I. Agreement between questionnaire data and medical records of chronic diseases in middle-aged and elderly Finnish men and women. Am J Epidemiol. 1997;145:762–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Hernelahti M, Kujala UM, Kaprio J, Karjalainen J, Sarna S. Hypertension in master endurance athletes. J Hypertens. 1998;16:1573–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Kujala UM, Kaprio J, Sarna S, Koskenvuo M. Relationship of leisure-time physical activity and mortality: the Finnish twin cohort. JAMA. 1998;279:440–4.CrossRefPubMedGoogle Scholar
  27. 27.
    Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278:1349–56.CrossRefPubMedGoogle Scholar
  28. 28.
    SNPedia. ApoE. 2011;2011.Google Scholar
  29. 29.
    Williams RL. A note on robust variance estimation for cluster-correlated data. Biometrics. 2000;56:645–6.CrossRefPubMedGoogle Scholar
  30. 30.
    UCLA: Academic Technology Services, statistical consulting group. Stata FAQ: How do I use xi3?;2011.Google Scholar
  31. 31.
    Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49:1373–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Glaziou P. Sampsize home page. 2005;2011.Google Scholar
  33. 33.
    Virtaa JJ, Jarvenpaa T, Heikkila K, Perola M, Koskenvuo M, Raiha I, et al. Midlife alcohol consumption and later risk of cognitive impairment: a twin follow-up study. J Alzheimers Dis. 2010;22:939–48.PubMedGoogle Scholar
  34. 34.
    Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol. 2005;62:1556–60.CrossRefPubMedGoogle Scholar
  35. 35.
    Laitala VS, Kaprio J, Koskenvuo M, Raiha I, Rinne JO, Silventoinen K. Association and causal relationship of midlife obesity and related metabolic disorders with old age cognition. Curr Alzheimer Res 2011:699–706.Google Scholar
  36. 36.
    Xu WL, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midlife overweight and obesity increase late-life dementia risk: a population-based twin study. Neurology. 2011;76:1568–74.CrossRefPubMedGoogle Scholar
  37. 37.
    Petrovitch H, White LR, Izmirilian G, Ross GW, Havlik RJ, Markesbery W, et al. Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu-Asia aging Study. Neurobiol Aging. 2000;21:57–62.PubMedGoogle Scholar
  38. 38.
    Sparks DL, Liu H, Scheff SW, Coyne CM, Hunsaker JC III. Temporal sequence of plaque formation in the cerebral cortex of non-demented individuals. J Neuropathol Exp Neurol. 1993;52:135–42.CrossRefPubMedGoogle Scholar
  39. 39.
    Gorelick PB. Status of risk factors for dementia associated with stroke. Stroke. 1997;28:459–63.CrossRefPubMedGoogle Scholar
  40. 40.
    Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA. 1997;277:813–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD. Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer’s disease. Lancet. 1999;354:919–20.CrossRefPubMedGoogle Scholar
  42. 42.
    Harvey J. Leptin: a multifaceted hormone in the central nervous system. Mol Neurobiol. 2003;28:245–58.CrossRefPubMedGoogle Scholar
  43. 43.
    Dishman RK, Berthoud HR, Booth FW, Cotman CW, Edgerton VR, Fleshner MR, et al. Neurobiology of exercise. Obesity (Silver Spring). 2006;14:345–56.CrossRefGoogle Scholar
  44. 44.
    Craft S. Insulin resistance syndrome and Alzheimer’s disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol Aging. 2005;26(Suppl 1):65–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Kaprio J, Silventoinen K. Advanced methods in Twin studies. In: (ed), Genetic Epidemiology. New York, USA: Humana Press, c/o Springer Science + Business Media, 2011:143–152.Google Scholar
  46. 46.
    Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology. 2000;54:S4–9.CrossRefPubMedGoogle Scholar
  47. 47.
    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;34:939–44.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Jyri J. Virta
    • 1
    • 2
  • Kauko Heikkilä
    • 2
  • Markus Perola
    • 6
    • 7
  • Markku Koskenvuo
    • 2
  • Ismo Räihä
    • 4
    • 5
  • Juha O. Rinne
    • 1
    • 8
  • Jaakko Kaprio
    • 2
    • 3
    • 6
  1. 1.Turku PET CentreUniversity of Turku and Turku University HospitalTurkuFinland
  2. 2.Department of Public Health, Hjelt InstituteUniversity of HelsinkiHelsinkiFinland
  3. 3.Department of Mental Health and Substance Abuse ServicesNational Institute for Health and WelfareHelsinkiFinland
  4. 4.Institute of Clinical Medicine, Family MedicineUniversity of TurkuTurkuFinland
  5. 5.Department of Internal MedicineTurku City HospitalTurkuFinland
  6. 6.Institute for Molecular MedicineHelsinkiFinland
  7. 7.Unit for Genetic EpidemiologyNational Institute for Health and WelfareHelsinkiFinland
  8. 8.Department of NeurologyUniversity of Turku and Turku University HospitalTurkuFinland

Personalised recommendations