Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Association between total cerebral small vessel disease score and cognitive function in patients with vascular risk factors

Hypertension Research volume 46, pages 1326–1334 (2023)Cite this article

Abstract

Hypertension is the most important risk factor for cerebral small vessel disease (SVD). In this cross-sectional study, we tested the independent association of cerebral SVD burden with global cognitive function and each cognitive domain in patients with vascular risk factors. The Tokyo Women’s Medical University Cerebral Vessel Disease (TWMU CVD) registry is an ongoing prospective, observational registry in which patients with any evidence of CVD in magnetic resonance imaging (MRI) and at least one vascular risk factor were consecutively enrolled. For SVD-related findings, we evaluated white matter hyperintensity, lacunar infarction, cerebral microbleeds, enlarged perivascular space, and medial temporal atrophy. We used the total SVD score as the SVD burden. They underwent the Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests, and each cognitive domain was evaluated. After excluding patients without MRI T2* images and those with MMSE score <24, we analyzed 648 patients. The total SVD score was significantly associated with MMSE and MoCA-J scores. After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and MoCA-J score remained significant. The total SVD score was independently associated with attention. In conclusion, the total SVD score, cerebral SVD burden, was independently association with global cognitive function and attention. A strategy to reduce SVD burden will have the potential to prevent cognitive decline.

A total of 648 patients with any evidence of cerebral small vessel disease (SVD) in MRI and at least one vascular risk factor underwent Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests. The total SVD scores count the presence of each SVD-related findings (white matter hyperintensity, Lacunar infarction, cerebral microbleeds and enlarged perivascular space), ranging from 0 to 4, as the SVD burden. Total SVD scores were significantly associated with MoCA-J scores (r = −0.203, P < 0.001). After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and global cognitive scores remained significant.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Vermeer SE, Longstreth WT Jr, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurol. 2007;6:611–9.

    Article  PubMed  Google Scholar 

  2. Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2010;341:c3666.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Akoudad S, Portegies MLP, Koudstaal PJ, Hofman A, van der Lugt A, Ikram MA, et al. Cerebral microbleeds are associated with an increased risk of stroke: the Rotterdam Study. Circulation. 2015;132:509–16.

    Article  PubMed  Google Scholar 

  4. Akoudad S, Wolters FJ, Viswanathan A, de Bruijn EF, van der Lugt A, Hofman A, et al. Association of cerebral microbleeds with cognitive decline and dementia. JAMA Neurol. 2016;73:934–43.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hamilton OKL, Backhouse EV, Janssen E, Jochems ACC, Maher C, Ritakari TE, et al. Cognitive impairment in sporadic cerebral small vessel disease: a systematic review and meta-analysis. Alzheimers Dement. 2021;17:665–85.

    Article  PubMed  Google Scholar 

  6. Kitagawa K. Blood pressure management for secondary stroke prevention. Hypertens Res. 2022;45:936–43.

    Article  PubMed  Google Scholar 

  7. Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12:822–38.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zamboni G, Griffanti L, Jenkinson M, Mazzucco S, Li L, Küker W, et al. White matter imaging correlates of early cognitive impairment detected by the montreal cognitive assessment after transient ischemic attack and minor stroke. Stroke. 2017;48:1539–47.

    Article  CAS  PubMed  Google Scholar 

  9. Hoshi T, Yamagami H, Furukado S, Miwa K, Tanaka M, Sakaguchi M, et al. Serum inflammatory proteins and frontal lobe dysfunction in patients with cardiovascular risk factors. Eur J Neurol. 2010;17:1134–40.

    Article  CAS  PubMed  Google Scholar 

  10. Yakushiji Y, Nishiyama M, Yakushiji S, Hirotsu T, Uchino A, Nakajima J, et al. Brain microbleeds and global cognitive function in adults without neurological disorder. Stroke. 2008;39:3323–8.

    Article  PubMed  Google Scholar 

  11. Hilal S, Tan CS, Adams HHH, Habes M, Mok V, Venketasubramanian N, et al. Enlarged perivascular spaces and cognition: a meta-analysis of 5 population-based studies. Neurology. 2018;91:e832–e842.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Huijts M, Duits A, van Oostenbrugge RJ, Kroon AA, de Leeuw PW, Staals J. Accumulation of MRI markers of cerebral small vessel disease is associated with decreased cognitive function. a study in first-ever lacunar stroke and hypertensive patients. Front Aging Neurosci. 2013;5:72.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Klarenbeek P, van Oostenbrugge RJ, Rouhl RP, Knottnerus IL, Staals J. Ambulatory blood pressure in patients with lacunar stroke: association with total MRI burden of cerebral small vessel disease. Stroke 2013;44:2995–9.

    Article  PubMed  Google Scholar 

  14. Staals J, Makin SD, Doubal FN, Dennis MS, Wardlaw JM. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. 2014;83:1228–34.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Staals J, Booth T, Morris Z, Bastin ME, Gow AJ, Corley J, et al. Total MRI load of cerebral small vessel disease and cognitive ability in older people. Neurobiol Aging. 2015;36:2806–11.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Uiterwijk R, van Oostenbrugge RJ, Huijts M, De Leeuw PW, Kroon AA, Staals J. Total cerebral small vessel disease MRI score is associated with cognitive decline in executive function in patients with hypertension. Front Aging Neurosci. 2016;8:301.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lau KK, Li L, Schulz U, Simoni M, Chan KH, Ho SL, et al. Total small vessel disease score and risk of recurrent stroke: Validation in 2 large cohorts. Neurology. 2017;88:2260–7.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yilmaz P, Ikram MK, Niessen WJ, Ikram MA, Vernooij MW. Practical small vessel disease score relates to stroke, dementia, and death. Stroke. 2018;49:2857–65.

    Article  PubMed  Google Scholar 

  19. Suzuyama K, Yakushiji Y, Ogata A, Nishihara M, Eriguchi M, Kawaguchi A, et al. Total small vessel disease score and cerebro-cardiovascular events in healthy adults: the Kashima scan study. Int J Stroke. 2020;15:973–9.

    Article  PubMed  Google Scholar 

  20. Zhi N, Zhang L, Wang Y, Bai S, Geng J, Yu L, et al. Modified cerebral small vessel disease score is associated with vascular cognitive impairment after lacunar stroke. Aging. 2021;13:9510–21.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Serrano-Pozo A, Growdon JH. Is Alzheimer’s disease risk modifiable? J Alzheimers Dis. 2019;67:795–819.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Frisoni GB, Fox NC, Jack CR Jr, Scheltens P, Thompson PM. The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol. 2010;6:67–77.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Litak J, Mazurek M, Kulesza B, Szmygin P, Litak J, Kamieniak P, et al. Cerebral small vessel disease. Int J Mol Sci. 2020;21:9729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kubota M, Iijima M, Shirai Y, Toi S, Kitagawa K. Association between cerebral small vessel disease and central motor conduction time in patients with vascular risk. J Stroke Cerebrovasc Dis. 2019;28:2343–50.

    Article  PubMed  Google Scholar 

  25. Seki M, Yoshizawa H, Hosoya M, Kitagawa K. Neuropsychological profile of early cognitive impairment in cerebral small vessel disease. Cerebrovasc Dis. 2022;51:600–7.

    Article  CAS  PubMed  Google Scholar 

  26. Fujiwara Y, Suzuki H, Yasunaga M, Sugiyama M, Ijuin M, Sakuma N, et al. Brief screening tool for mild cognitive impairment in older Japanese: validation of the Japanese version of the Montreal Cognitive Assessment. Geriatr Gerontol Int. 2010;10:225–32.

    Article  PubMed  Google Scholar 

  27. Kim GH, Kim JE, Choi KG, Lim SM, Lee JM, Na DL, et al. T1-weighted axial visual rating scale for an assessment of medial temporal atrophy in Alzheimer’s disease. J Alzheimers Dis. 2014;41:169–78.

    Article  PubMed  Google Scholar 

  28. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. Am J Roentgenol. 1987;149:351–6.

    Article  CAS  Google Scholar 

  29. Doubal FN, MacLullich AMJ, Ferguson KJ, Dennis MS, Wardlaw JM. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke. 2010;41:450–4.

    Article  PubMed  Google Scholar 

  30. Vasquez BP, Zakzanis KK. The neuropsychological profile of vascular cognitive impairment not demented: a meta-analysis. J Neuropsychol. 2015;9:109–36.

    Article  PubMed  Google Scholar 

  31. Ishikawa H, Meguro K, Ishii H, Tanaka N, Yamaguchi S. Silent infarction or white matter hyperintensity and impaired attention task scores in a nondemented population: the Osaki-Tajiri Project. J Stroke Cerebrovasc Dis. 2012;21:275–82.

    Article  PubMed  Google Scholar 

  32. Carey CL, Kramer JH, Josephson SA, Mungas D, Reed BR, Schuff N, et al. Subcortical lacunes are associated with executive dysfunction in cognitively normal elderly. Stroke. 2008;39:397–402.

    Article  PubMed  Google Scholar 

  33. Hirao K, Yamashita F, Tsugawa A, Haime R, Fukasawa R, Sato T, et al. Association of white matter hyperintensity progression with cognitive decline in patients with amnestic mild cognitive impairment. J Alzheimers Dis. 2021;80:877–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jiang J, Yao K, Huang X, Zhang Y, Shen F, Weng S. Longitudinal white matter hyperintensity changes and cognitive decline in patients with minor stroke. Aging Clin Exp Res. 2022;34:1047–54.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Funding

This work was supported in part by Research Funding of Longevity Sciences (28-15, 30-1) from the National Center for Geriatrics and Gerontology, the Japan.

Author information

Authors and Affiliations

  1. Department of Neurology, Tokyo Women’s Medical University Hospital, Tokyo, Japan

    Megumi Hosoya, Sono Toi, Misa Seki, Moeko Saito, Takao Hoshino, Hiroshi Yoshizawa & Kazuo Kitagawa

Authors
  1. Megumi Hosoya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sono Toi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Misa Seki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moeko Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takao Hoshino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroshi Yoshizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kazuo Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kazuo Kitagawa.

Ethics declarations

Conflict of interest

KK reports personal fees from Daiichi Sankyo, Kyowa Kirin and Kowa. Others have nothing to disclose.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hosoya, M., Toi, S., Seki, M. et al. Association between total cerebral small vessel disease score and cognitive function in patients with vascular risk factors. Hypertens Res 46, 1326–1334 (2023). https://doi.org/10.1038/s41440-023-01244-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-023-01244-8

Keywords

This article is cited by

Search

Advanced search

Quick links