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Glymphatic system impairment in Alzheimer’s disease: associations with perivascular space volume and cognitive function

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Abstract

Objectives

To investigate glymphatic function in Alzheimer’s disease (AD) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and to explore the associations between DTI-ALPS index and perivascular space (PVS) volume, as well as between DTI-ALPS index and cognitive function.

Methods

Thirty patients with PET-CT-confirmed AD (15 AD dementia; 15 mild cognitive impairment due to AD) and 26 age- and sex-matched cognitively normal controls (NCs) were included in this study. All participants underwent neurological MRI and cognitive assessments. Bilateral DTI-ALPS indices were calculated. PVS volume fractions were quantitatively measured at three locations: basal ganglia (BG), centrum semiovale, and lateral ventricle body level. DTI-ALPS index and PVS volume fractions were compared among three groups; correlations among the DTI-ALPS index, PVS volume fraction, and cognitive scales were analyzed.

Results

Patients with AD dementia showed a significantly lower DTI-ALPS index in the whole brain (p = 0.009) and in the left hemisphere (p = 0.012) compared with NCs. The BG-PVS volume fraction in patients with AD was significantly larger than the fraction in NCs (p = 0.045); it was also negatively correlated with the DTI-ALPS index (r =  − 0.433, p = 0.021). Lower DTI-ALPS index was correlated with worse performance in the Boston Naming Test (β = 0.515, p = 0.008), Trail Making Test A (β =  − 0.391, p = 0.048), and Digit Span Test (β = 0.408, p = 0.038).

Conclusions

The lower DTI-ALPS index was found in patients with AD dementia, which may suggest impaired glymphatic system function. DTI-ALPS index was correlated with BG-PVS enlargement and worse cognitive performance in certain cognitive domains.

Clinical relevance statement

Diffusion tensor image analysis along the perivascular space index may be applied as a useful indicator to evaluate the glymphatic system function. The impaired glymphatic system in patients with Alzheimer’s disease (AD) dementia may provide a new perspective for understanding the pathophysiology of AD.

Key Points

• Patients with Alzheimer’s disease dementia displayed a lower diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, possibly indicating glymphatic impairment.

• A lower DTI-ALPS index was associated with the enlargement of perivascular space and cognitive impairment.

• DTI-ALPS index could be a promising biomarker of the glymphatic system in Alzheimer’s disease dementia.

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Abbreviations

AD:

Alzheimer’s disease

ANOVA:

Analysis of variance

AQ:

The Alzheimer’s Questionnaire

BG:

Basal ganglia

BNT:

Boston Naming Test

CDR:

Clinical Dementia Rating

CDT:

Clock Drawing Test

CI:

Confidence interval

CSO:

Centrum semiovale

DST:

Digit Span Test

DTI-ALPS:

Diffusion tensor image analysis along the perivascular space

IQR:

Interquartile range

LVB:

Lateral ventricle body

MCI:

Mild cognitive impairment

MMSE:

Mini-Mental State Examination

MoCA:

Montreal Cognitive Assessment

NC:

Normal control

NPI:

Neuropsychiatric Inventory

PVS:

Perivascular space

RAVLT:

Rey Auditory Verbal Learning Test

ROI:

Region of interest

SDMT:

Symbol Digit Modalities Test

TMT :

Trail Making Test

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Funding

This study is supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB39000000) and the Beijing Municipal Science and Technology Commission (Grant No. Z181100001518005).

Author information

Authors and Affiliations

  1. Tiantan Neuroimaging Center of Excellence, China National Clinical Research Center for Neurological Diseases, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, No.119 South Fourth Ring West Road, Beijing, China

    Xue Zhang, Yingkui Zhang, Xiaoyan Bai, Zhiye Li & Binbin Sui

  2. Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Xue Zhang, Xiaoyan Bai & Zhiye Li

  3. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Yue Wang, Jiong Shi & Shiping Li

  4. China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Yue Wang, Jiong Shi & Shiping Li

  5. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China

    Yue Wang, Jiong Shi & Shiping Li

  6. Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrument Science, Zhejiang University, No.38, Zheda Road, Hangzhou, China

    Bingjie Jiao & Ruiliang Bai

  7. Department of Radiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China

    Zhongyan Wang

  8. Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Shumen Shaw Hospital and Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China

    Ruiliang Bai

  9. MOE Frontier Science Center for Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China

    Ruiliang Bai

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  1. Xue Zhang
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Corresponding authors

Correspondence to Shiping Li, Ruiliang Bai or Binbin Sui.

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Guarantor

The scientific guarantor of this publication is Binbin Sui.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained. The study protocol was approved by the human ethics committee of Beijing Tiantan Hospital (no. KY 2019–004-007).

Study subjects or cohorts overlap

Our study subjects or cohorts have not been previously reported.

Methodology

• Retrospective

• Cross-sectional study

• Performed at one institution

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Xue Zhang and Yue Wang contributed equally to this work as first authors.

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Zhang, X., Wang, Y., Jiao, B. et al. Glymphatic system impairment in Alzheimer’s disease: associations with perivascular space volume and cognitive function. Eur Radiol 34, 1314–1323 (2024). https://doi.org/10.1007/s00330-023-10122-3

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