Skip to main content
Download PDF
  • Research Article
  • Open access
  • Published:

The Association between Homocysteine, Arterial Stiffness and Executive Function Middle-age and Older Women

Artery Research volume 27, pages 32–37 (2021)Cite this article

Abstract

Age-related decreases in executive function and an increase in arterial stiffness and plasma homocysteine levels are related to the risk of dementia. However, the association between executive function, arterial stiffness, and homocysteine levels remains unclear. This study aimed to investigate the relationship between executive function, arterial stiffness, and plasma homocysteine in 82 middle-aged and older women. The Stroop interference time, Brachial-ankle Pulse Wave Velocity (baPWV), and plasma homocysteine concentration were collected. The correlation analyses revealed that the Stroop interference time was significantly correlated with plasma homocysteine (r = 0.40, p < 0.001) and baPWV (r = 0.38, p = 0.001). In addition, plasma homocysteine levels were significantly correlated with baPWV (r = 0.48, p < 0.001). In the mediated analyses, the plasma homocysteine level directly (β = 0.24; p = 0.037) and indirectly (β = 0.12, 95% confidence interval [0.007, 0.238]) affected the Stroop interference time. These results suggest that higher plasma homocysteine levels are associated with a decline in executive function mediated by higher artery stiffness in middle-aged and older women.

References

  1. Sperling R, Mormino E, Johnson K. The evolution of preclinical Aizheimer’s disease: implications for prevention trials. Neuron 2014;84:608–22.

    Google Scholar 

  2. Satizabal CL, Beiser AS, Chouraki V, Chêne G, Dufouil C, Seshadri S. Incidence of dementia over three decades in the Framingham Heart Study. N Engl J Med 2016;374:523–32.

    Google Scholar 

  3. Forte R, Boreham CAG, De Vito G, Pesce C. Health and quality of life perception in older adults: the joint role of cognitive efficiency and functional mobility. Int J Environ Res Public Health 2015;12:11328–44.

    Google Scholar 

  4. de la Torre JC. Critically attained threshold of cerebral hypoperfusion: the CATCH hypothesis of Alzheimer’s pathogenesis. Neurobiol Aging 2000;21:331–42.

    Google Scholar 

  5. Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, et al. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 2005;57:789–94.

    Google Scholar 

  6. Tarumi T, Ayaz Khan M, Liu J, Tseng BY, Parker R, Riley J, et al. Cerebral hemodynamics in normal aging: Central artery stiffness, wave reflection, and pressure pulsatility. J Cereb Blood Flow Metab 2014;34:971–8.

    Google Scholar 

  7. DuBose LE, Voss MW, Weng TB, Kent JD, Dubishar KM, Lane-Cordova A, et al. Carotid β-stiffness index is associated with slower processing speed but not working memory or white matter integrity in healthy middle-aged/older adults. J Appl Physiol 2017;122:868–76.

    Google Scholar 

  8. Hamasaki A, Akazawa N, Yoshikawa T, Myoenzono K, Tagawa K, Sawano Y, et al. Central artery stiffness is related to cerebral oxygenation hemodynamics during executive function tasks in healthy middle-aged and older adults. Exp Gerontol 2018;114:93–8.

    Google Scholar 

  9. Li R, Singh M. Sex differences in cognitive impairment and Alzheimer’s disease. Front Neuroendocrinol 2014;35:385–403.

    Google Scholar 

  10. Mudd SH, Finkelstein JD, Refsum H, Ueland PM, Malinow MR, Lentz SR, et al. Homocysteine and its disulfide derivatives: a suggested consensus terminology. Arterioscler Thromb Vasc Biol 2000;20:1704–6.

    Google Scholar 

  11. Mujumdar VS, Aru GM, Tyagi SC. Induction of oxidative stress by homocyst(e)ine impairs endothelial function. J Cell Biochem 2001;82:491–500.

    Google Scholar 

  12. Welch GN, Loscalzo J. Homocyteine and atherothrombosis. N Engl J Med 1998;338:1042–50.

    Google Scholar 

  13. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, et al. A prospective study of plasma homocyst(e) ine and risk of myocardial infarction in US physicians. JAMA 1992;268:877–81.

    Google Scholar 

  14. Nygård O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, et al. Total plasma homocysteine and cardiovascular risk profile: the Hordaland Homocysteine Study. JAMA 1995;274:1526–33.

    Google Scholar 

  15. Verhoef P, Hennekens CH, Malinow MR, Kok FJ, Willett WC, Stampfer MJ. A prospective study of plasma homocyst(e)ine and risk of ischemic stroke. Stroke 1994;25:1924–30.

    Google Scholar 

  16. Bell IR, Edman JS, Selhub J, Morrow FD, Marby DW, Kayne HL, et al. Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people. Acta Psychiatr Scand 1992;86:386–90.

    Google Scholar 

  17. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325:1202.

    Google Scholar 

  18. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346:476–83.

    Google Scholar 

  19. Duthie SJ, Whalley LJ, Collins AR, Leaper S, Berger K, Deary IJ. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 2002;75:908–13.

    Google Scholar 

  20. Garcia A, Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ 2004;171:897–904.

    Google Scholar 

  21. Mooijaart SP, Gussekloo J, Frölich M, Jolles J, Stott DJ, Westendorp RG, et al. Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study. Am J Clin Nutr 2005;82:866–71.

    Google Scholar 

  22. Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643–62.

    Google Scholar 

  23. Akazawa N, Hamasaki A, Tanahashi K, Kosaki K, Yoshikawa T, Myoenzono K, et al. Lactotripeptide ingestion increases cerebral blood flow velocity in middle-aged and older adults. Nutr Res 2018;53:61–6.

    Google Scholar 

  24. Yamashina A, Tomiyama H, Takeda K, Tsuda H, Arai T, Hirose K, et al. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res 2002;25:359–64.

    Google Scholar 

  25. Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods 2008;40:879–91.

    Google Scholar 

  26. Kalmijn S, Launer LJ, Lindemans J, Bots ML, Hojman A, Breteler MM. Total homocysteine and cognitive decline in a community-based sample of elderly subjects: the Rotterdam Study. Am J Epidemiol 1999;150:283–9.

    Google Scholar 

  27. Cheng D, Kong H, Pang W, Yang H, Lu H, Huang C, et al. B vitamin supplementation improves cognitive function in the middle aged and elderly with hyperhomocysteinemia. Nutr Neurosci 2016;19:461–6.

    Google Scholar 

  28. Prins ND, Den Heijer T, Hofman A, Koudstaal PJ, Jolles J, Clarke R, et al. Homocysteine and cognitive function in the elderly: the Rotterdam scan study. Neurology 2002;59:1375–80.

    Google Scholar 

  29. Lewerin C, Matousek M, Steen G, Johansson B, Steen B, Nilsson-Ehle H. Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study. Am J Clin Nutr 2005;81:1155–62.

    Google Scholar 

  30. Hofmann MA, Lalla E, Lu Y, Gleason MR, Wolf BM, Tanji N, et al. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest 2001;107:675–83.

    Google Scholar 

  31. Chen L, Wang B, Wang J, Ban Q, Wu H, Song Y, et al. Association between serum total homocysteine and arterial stiffness in adults: a community-based study. J Clin Hypertens 2018;20:686–93.

    Google Scholar 

  32. Waldstein, SR, Rice SC, Thayer JF, Najjar SS, Scuteri A, Zonderman AB. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension 2008;51:99–104.

    Google Scholar 

  33. Taniguchi Y, Fujiwara Y, Nofuji Y, Nishi M, Murayama H, Seino S, et al. Prospective study of arterial stiffness and subsequent cognitive decline among community-dwelling older Japanese. J Epidemiol 2015;25:592–9.

    Google Scholar 

  34. Gutierrez J, Marshall RS, Lazar RM. Indirect measures of arterial stiffness and cognitive performance in individuals without traditional vascular risk factors or disease. JAMA Neurol 2015;72:309–15.

    Google Scholar 

  35. Fernando MS, Simpson JE, Matthews F, Brayne C, Lewis CE, Barber R, et al. White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury. Stroke 2006;37:1391–8.

    Google Scholar 

  36. Moody DM, Bell MA, Challa VR. Features of the cerebral vascular pattern that predict vulnerability to perfusion or oxygenation deficiency: an anatomic study. AJNR Am J Neuroradiol 1990;11:431–9.

    Google Scholar 

  37. Blacher J, Demuth K, Guerin AP, Safar ME, Moatti N, London GM. Influence of biochemical alterations on arterial stiffness in patients with end-stage renal disease. Aeterioscler Thromb Vasc Biol 1998;18:535–41.

    Google Scholar 

  38. Stamler JS and Loscalzo J. Endothelium-derived relaxing factor modulates the atherothrobogenic effect of homocysteine. J Cardiovasc Pharmacol 1992;20:S202–S4.

    Google Scholar 

  39. Wakabayashi I. Homocysteine levels and arterial stiffness in the general population. J Atheros Thromb 2016;23:668–70.

    Google Scholar 

  40. Bostom AG, Shemin D, Lapane KL, Miller JW, Sutherland P, Nadeau M, et al. Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study. Atherosclerosis 1995;114:93–103.

    Google Scholar 

  41. Dennis VW, Robinson K. Homocysteinemia and vascular disease in end-stage renal disease. Kidney Int Suppl 1996;57:S11–S17.

    Google Scholar 

Download references

Author information

Author notes

  1. Ai Shindo-Hamasaki

    Present address: Department of Physical Therapy, Faculty of Medical and Health Sciences, Tsukuba International University, 6-8-33, Manabe, Tsuchiura, Ibaraki, Japan

  2. Nobuhiko Akazawa

    Present address: Department of Sports Research, Japan Institute of Sport Sciences, 3-15-1 Nishigaoka, Kitaku, Tokyo, Japan

Authors and Affiliations

  1. Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennodai, Ibaraki, Japan

    Ai Shindo-Hamasaki, Nobuhiko Akazawa, Reiko Momma & Seiji Maeda

Authors
  1. Ai Shindo-Hamasaki
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Nobuhiko Akazawa
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Reiko Momma
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Seiji Maeda
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Seiji Maeda.

Additional information

Peer review under responsibility of the Association for Research into Arterial Structure and Physiology

Data availability statement: The data that support the findings of this study are available from the corresponding author, SM, upon reasonable request.

Rights and permissions

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shindo-Hamasaki, A., Akazawa, N., Momma, R. et al. The Association between Homocysteine, Arterial Stiffness and Executive Function Middle-age and Older Women. Artery Res 27, 32–37 (2021). https://doiorg.publicaciones.saludcastillayleon.es/10.2991/artres.k.201102.003

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.2991/artres.k.201102.003

Keywords

Artery Research

ISSN: 1876-4401

Contact us