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 Jul 1;15(7):6160-6174.
doi: 10.21037/qims-2025-96. Epub 2025 Jun 23.

Association of magnetic resonance imaging glymphatic function with gray matter volume loss and cognitive impairment in Alzheimer's disease: a diffusion tensor image analysis along the perivascular space (DTI-ALPS) study

Qian Zhang #  1 , Chao-Gang Wei #  1 , Chong Cui #  1 , Ting Huang  1 , Shan-Wen Liu  2 , Meng Li  1 , Yu-Qi Zhi  1 , Xiao-Yun Liang  3   4 , Hua Hu  2 , Zhen Jiang  1 , Jiang-Tao Zhu  1 , Rong Liu  1
Affiliations

Association of magnetic resonance imaging glymphatic function with gray matter volume loss and cognitive impairment in Alzheimer's disease: a diffusion tensor image analysis along the perivascular space (DTI-ALPS) study

Qian Zhang et al. Quant Imaging Med Surg. .

Abstract

Background: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been used for diagnosing Alzheimer's disease (AD); however, few studies have examined the relationship between the DTI-ALPS index and cortical metrics, and the differentiation between AD severity levels remains unclear. This study aimed to explore the differences in DTI-ALPS index and cortex among AD patients with varying severities and to analyze the interactions between DTI-ALPS index, cortical metrics, and cognitive function.

Methods: A total of 19 individuals with mild cognitive impairment (MCI), 17 individuals exhibiting mild AD, 25 individuals with moderate AD, and 28 healthy controls (HC) who were matched for age, sex, and education level were recruited. All the participants underwent diffusion tensor imaging (DTI) magnetic resonance imaging (MRI), followed by the calculation of the DTI-ALPS index to assess lymphatic system function. FreeSurfer (v7.4.1) was used to calculate thickness, volume, local gyre index, and area. One-way analysis of variance (ANOVA) was performed to compare the differences among HC, MCI, mild AD, and moderate AD groups. Pearson correlation analysis was employed to investigate the connection between the DTI-ALPS index and cognitive function, along with cortical metrics.

Results: The HC, MCI, mild AD, and moderate AD groups exhibited significant differences in the DTI-ALPS index of the left hemisphere (P=0.008), whereas 13 cortical metrics revealed a statistical significance between groups (P<0.05). In the left hemisphere, the DTI-ALPS index showed a positive trend with the Montreal Cognitive Assessment (MoCA) score (r=0.397, P<0.001). Higher DTI-ALPS was also associated with an increase in 10 cortical metrics after controlling for age, sex, and education.

Conclusions: There is a significant relationship between the DTI-ALPS index, cortical metrics, and cognitive function. This result may suggest that lymphatic dysfunction indicated by the DTI-ALPS index could mirror cortical structural degeneration and cognitive decline within the pathological process of AD. DTI-ALPS can be used as an indicator of structural degeneration and decline in cognitive function in AD.

Keywords: Alzheimer’s disease (AD); cerebral cortex; cortical index; diffusion magnetic resonance imaging (diffusion MRI); glymphatic system (GS).

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-2025-96/coif). X.Y.L. reports that he was employed by Neusoft Medical Systems Co., Ltd. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Patient enrollment flow diagram. AD, Alzheimer’s disease; MCI, mild cognitive impairment; MRI, magnetic resonance imaging.
Figure 2
Figure 2
Four spherical ROIs were placed within the projection fibers and association fibers on a color-coded FA map in bilateral hemispheres. FA, fractional anisotropy; ROIs, regions of interest.
Figure 3
Figure 3
Differences in the DTI-ALPS index of the left hemisphere among the HC, MCI, AD1, and AD2 groups. *, P<0.05; **, P<0.01. AD1, mild Alzheimer’s disease; AD2, moderate Alzheimer’s disease; ALPS, analysis along the perivascular space; DTI, diffusion tensor image; HC, healthy control; MCI, mild cognitive impairment.
Figure 4
Figure 4
Illustration of brain region clusters at which 13 cortical metrics revealed a statistical significance among the HC, MCI, AD1, and AD2 groups, including: (A-D) brain region clusters with significant inter-group differences in cortical thickness; (E) brain region cluster with significant inter-group differences in cortical LGI; (F) brain region cluster with significant inter-group differences in cortical area; (G-M) brain region clusters with significant inter-group differences in cortical volume. The color bar represents −log10CWP; with red and yellow indicating HC group > MCI, AD1, and AD2 groups. AD1, mild Alzheimer’s disease; AD2, moderate Alzheimer’s disease; CWP, composite-weighted P value; HC, healthy control; IPL, inferior parietal lobule; IT, inferior temporal; LG, lingual gyrus; LGI, local gyre index; lOFC, lateral orbitofrontal cortex; MCI, mild cognitive impairment; MT, middle temporal; ST, superior temporal.
Figure 5
Figure 5
Differences in 13 cortical metrics between HC, MCI, AD1, and AD2 groups. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001. AD1, mild Alzheimer’s disease; AD2, moderate Alzheimer’s disease; HC, healthy control; LGI, local gyre index; lh, left hemisphere; MCI, mild cognitive impairment; rh, right hemisphere.
Figure 6
Figure 6
Correlation between the DTI-ALPS index in left hemispheres, cortical metrics, and cognitive function. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001. ALPS, analysis along the perivascular space; DTI, diffusion tensor image; LGI, local gyre index; lh, left hemisphere; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; rh, right hemisphere.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Zhang H, Wei W, Zhao M, Ma L, Jiang X, Pei H, Cao Y, Li H. Interaction between Aβ and Tau in the Pathogenesis of Alzheimer's Disease. Int J Biol Sci 2021;17:2181-92. 10.7150/ijbs.57078 - DOI - PMC - PubMed
    1. Goodman JR, Adham ZO, Woltjer RL, Lund AW, Iliff JJ. Characterization of dural sinus-associated lymphatic vasculature in human Alzheimer's dementia subjects. Brain Behav Immun 2018;73:34-40. 10.1016/j.bbi.2018.07.020 - DOI - PMC - PubMed
    1. Preston JE. Ageing choroid plexus-cerebrospinal fluid system. Microsc Res Tech 2001;52:31-7. 10.1002/1097-0029(20010101)52:1<31::AID-JEMT5>3.0.CO;2-T - DOI - PubMed
    1. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 2012;4:147ra111. 10.1126/scitranslmed.3003748 - DOI - PMC - PubMed
    1. Lee S, Yoo RE, Choi SH, Oh SH, Ji S, Lee J, Huh KY, Lee JY, Hwang I, Kang KM, Yun TJ, Kim JH, Sohn CH. Contrast-enhanced MRI T1 Mapping for Quantitative Evaluation of Putative Dynamic Glymphatic Activity in the Human Brain in Sleep-Wake States. Radiology 2021;300:661-8. 10.1148/radiol.2021203784 - DOI - PubMed

LinkOut - more resources