Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 6;15(6):5496-5509.
doi: 10.21037/qims-24-1610. Epub 2025 May 23.

Association between deep gray matter iron deposition, white matter hyperintensity, and hypertensive cognitive impairment

Yu Su #  1   2   3 , Chungao Li #  1   2   3 , Ziji Qin  4 , Jiamin Kang  5 , Youzhi Wang  1   2   3 , Tingting Liu  1   2   3 , Jie Zhao  1   2   3 , Zhengdong Xiang  1   2   3 , Quan Chen  1   2   3 , Chuansheng Zheng  1   2   3 , E Mark Haacke  6   7 , Wenjun Wu  1   2   3 , Lixia Wang  1   2   3
Affiliations

Association between deep gray matter iron deposition, white matter hyperintensity, and hypertensive cognitive impairment

Yu Su et al. Quant Imaging Med Surg. .

Abstract

Background: Deep gray matter (DGM) iron deposition and white matter hyperintensity (WMH) often occur simultaneously in hypertensive patients. However, their relationship and effect on cognition in hypertension remain unclear. We aimed to investigate the correlation between DGM iron deposition, WMH, and cognitive impairment.

Methods: A total of 105 hypertensive patients and 31 age-, gender-, and education-matched healthy controls (HCs) were prospectively recruited for the study; the patients were divided into the hypertension with cognitive impairment (HTN-CI) group (n=55) and the hypertension without cognitive impairment (HTN-NCI) group (n=50). All participants underwent strategically acquired gradient echo (STAGE) imaging, and quantitative susceptibility mapping (QSM) was obtained. The global region (RI) and high-iron content region (RII) susceptibilities of the DGM were measured. The associations between WMH, iron deposition, and cognitive impairment were analyzed by partial correlation, univariate, multivariate linear regression, and exploratory mediation analyses.

Results: The RI or RII analysis results showed that the susceptibilities of the bilateral caudate nucleus (CN) head, thalamus (TH), and putamen (PU) differed significantly among the three groups (all P<0.05). Further, the RII susceptibilities of the bilateral red nucleus (RN) (left, r=0.312, P=0.023; right, r=0.336, P=0.014) and substantia nigra (SN) (left, r=0.347, P=0.011; right, r=0.316, P=0.021) were positively associated with the WMH scores. After adjusting for confounders, the model showed that decreased cognitive performance was associated with both increased WMH (β=-0.303, P=0.007) and susceptibilities of the left CN head (β=-0.450, P<0.001). WMH scores did not exhibit a significant mediation effect on the relationship between susceptibilities of the left CN head and cognition (P>0.05).

Conclusions: Both DGM iron deposition and WMH were found to be more pronounced in hypertension, and were negatively associated with cognitive function.

Keywords: Hypertension; cognitive impairment; iron; quantitative susceptibility mapping (QSM); white matter hyperintensity (WMH).

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1610/coif). E.M.H. was the founder and a board member of SpinTech MRI. E.M.H. has not been involved with SpinTech MRI for several years (since January, 2023); however, he does gold a very small percentage of shares in the company. His involvement in this study was strictly academic, and he did not receive any financial compensation or other benefits. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
QSM of a 62-year-old male (12). (A) The ROI was delineated on the QSM, including: 1, FWM; 2, CN head; 3, GP; 4, PU; 5, TH; 6, SN; 7, RN; 8, DN. (B) Diagram of the RI and RII region. The region inside the red line represents the RI of the right PU, and the purple region represents the distribution of the RII. CN, caudate nucleus; DN, dentate nucleus; FWM, frontal white matter; GP, globus pallidus; PU, putamen; QSM, quantitative susceptibility mapping; RI, global region; RII, high-iron content region; RN, red nucleus; ROI, region of interest; SN, substantia nigra; TH, thalamus.
Figure 2
Figure 2
The differences of susceptibilities (ppb) in the bilateral CN head, PU, and TH among the HTN-CI, HTN-NCI, and HC groups by RI and RII analyses. *, P<0.05; **, P<0.01. CN, caudate nucleus; HCs, healthy controls; HTN-CI, hypertension with cognitive impairment; HTN-NCI, hypertension without cognitive impairment; ppb, parts per billion; PU, putamen; RI, global region; RII, high-iron content region; TH, thalamus.
Figure 3
Figure 3
The positive association between the overall WMH scores and susceptibilities (ppb) of the HTN-CI group. (A) An association was found in the SN by the RI analysis. (B,C) An association was found in the RN and SN by the RII analysis. HTN-CI, hypertension with cognitive impairment; ppb, parts per billion; SN, substantia nigra; RI, global region; RII, high-iron content region; RN, red nucleus; WMH, white matter hyperintensity.
Figure 4
Figure 4
Exploratory mediation analysis. Top row: overall WMH does not mediate the relationship between the left CN head iron deposition and MoCA scores. Bottom row: DWMH does not mediate the relationship between the left CN head iron deposition and MoCA scores. CI, confidence interval; CN, caudate nucleus; DWMH, deep white matter hyperintensity; MoCA, Montreal Cognitive Assessment; WMH, white matter hyperintensity.
See this image and copyright information in PMC

References

    1. Ungvari Z, Toth P, Tarantini S, Prodan CI, Sorond F, Merkely B, Csiszar A. Hypertension-induced cognitive impairment: from pathophysiology to public health. Nat Rev Nephrol 2021;17:639-54. 10.1038/s41581-021-00430-6 - DOI - PMC - PubMed
    1. Inoue Y, Shue F, Bu G, Kanekiyo T. Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer's disease. Mol Neurodegener 2023;18:46. 10.1186/s13024-023-00640-5 - DOI - PMC - PubMed
    1. Garnier-Crussard A, Bougacha S, Wirth M, Dautricourt S, Sherif S, Landeau B, Gonneaud J, De Flores R, de la Sayette V, Vivien D, Krolak-Salmon P, Chételat G. White matter hyperintensity topography in Alzheimer's disease and links to cognition. Alzheimers Dement 2022;18:422-33. 10.1002/alz.12410 - DOI - PMC - PubMed
    1. Meng F, Yang Y, Jin G. Research Progress on MRI for White Matter Hyperintensity of Presumed Vascular Origin and Cognitive Impairment. Front Neurol 2022;13:865920. 10.3389/fneur.2022.865920 - DOI - PMC - PubMed
    1. Zhao X, Zuo M, Zhan F, Fan P, Liu S, Taylor M, Ganau M, Hall WA, Ruan H, Wan L. Cognition mediates the relationship between white matter hyperintensity and motor function in patients with cerebral small vessel disease: a cross-sectional study. Quant Imaging Med Surg 2024;14:7306-17. 10.21037/qims-24-1058 - DOI - PMC - PubMed

LinkOut - more resources