Diffusion along perivascular spaces reveals evidence supportive of glymphatic function impairment in Parkinson disease

McKnight, Colin D.; Trujillo, Paula; Lopez, Alexander M.; Petersen, Kalen J.; Considine, Ciaran M.; Lin, Ya-Chen; Yan, Yan; Kang, Hakmook; Donahue, Manus J.; Claassen, Daniel O.

doi:10.1016/j.parkreldis.2021.06.004

Cited by 90 publications

(84 citation statements)

References 16 publications

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“…They also suggested that ALPS index was robust under unified imaging method but was influenced by the imaging plane, the number of motion-proving gradient axes, and TE in the imaging sequence ( Taoka et al, 2021 ). Until present, there are only two studies using DTI-ALPS method to evaluate glymphatic system activity in patients with PD ( Chen et al, 2021 ; McKnight et al, 2021 ). Chen et al (2021) indicated that cognitively impaired patients with PD showed lower ALPS index than NCs.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, this method has been used in patients with dementia ( Steward et al, 2021 ), idiopathic normal pressure hydrocephalus (iNPH; Yokota et al, 2019 ; Bae et al, 2021 ), and type 2 diabetes mellitus ( Yang et al, 2020 ). To our knowledge, there are only two studies exploring the glymphatic system activity in patients with PD, using DTI-ALPS method ( Chen et al, 2021 ; McKnight et al, 2021 ). They highlighted that patients with PD with cognitive impairment showed lower ALPS index than normal controls (NCs).…”

Section: Introductionmentioning

confidence: 99%

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Diffusion Tensor Imaging Along the Perivascular Space Index in Different Stages of Parkinson’s Disease

et al. 2021

Front. Aging Neurosci.

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Background: The aim of this study was to evaluate the glymphatic system activity in patients with Parkinson’s disease (PD) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) methods.Methods: In total, 71 patients with idiopathic PD and 36 age- and sex-matched normal controls (NCs) were involved. Patients with PD were divided into early (n = 35) and late (n = 36) subgroups, based on Hoehn and Yahr (HY) stages. We calculated the diffusivity along the perivascular spaces (ALPS), as well as projection fibers and association fibers separately, to acquire the ALPS index. Enlarged perivascular spaces (EPVS) and periventricular white matter hyperintensities were also rated. Differences in ALPS index between the PD group and NCs and between two PD subgroups and NCs were compared. In addition, a multivariate logistic regression analysis was conducted to investigate the association between ALPS index and clinical variables.Results: Patients with PD revealed lower ALPS index than NCs (p = 0.010). The late PD group exhibited significantly lower ALPS index than NCs (p = 0.006). However, there were no marked differences noticed in ALPS index between NCs and early PD group and between the two PD subgroups. In the early PD group, there was a significantly positive correlation between ALPS index and Mini-Mental State Examination (MMSE) score (β = 0.021, p = 0.029) and a negative correlation between ALPS index and EPVS score (β = −0.050, p = 0.034), after controlling for multiple variables. In the late PD group, ALPS index was inversely associated with age (β = −0.012, p = 0.004).Conclusion: Impairment of the glymphatic system is involved in PD. DTI-ALPS index could be a promising biomarker of glymphatic system in PD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diffusion Tensor Imaging Along the Perivascular Space Index in Different Stages of Parkinson’s Disease

et al. 2021

Front. Aging Neurosci.

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“…Analysis along the perivascular space (ALPS) index is a diffusion metric derived from diffusion tensor imaging (DTI) ( Taoka et al, 2017 ). It estimates the diffusivity along with the perivascular spaces of medullary veins and has been used to assess glymphatic activity in clinical conditions including Alzheimer’s disease ( Taoka et al, 2017 ; Steward et al, 2021 ), normal pressure hydrocephalus ( Yokota et al, 2019 ; Bae et al, 2021 ), Parkinson’s disease ( Chen et al, 2021 ; McKnight et al, 2021 ), age-related iron deposition ( Zhou W. et al, 2020 ), diabetic-associated cognitive impairment ( Yang et al, 2020 ), and tumor-associated brain edema ( Toh et al, 2021 ; Toh and Siow, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Glymphatic Dysfunction in Patients With Ischemic Stroke

Toh

Siow

2021

Front. Aging Neurosci.

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Objectives: Rodent experiments have provided some insight into the changes of glymphatic function in ischemic stroke. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with ischemic stroke. We aimed to investigate the changes of glymphatic function in ischemic stroke and the factors associated with the changes.Materials and Methods: A total of 50 patients (mean age 56.7 years; 30 men) and 44 normal subjects (mean age 53.3 years; 23 men) who had preoperative diffusion-tensor imaging for calculation of the analysis along the perivascular space (ALPS) index were retrospectively included. Information collected from each patient included sex, age, time since stroke onset, infarct location, hemorrhagic change, infarct volume, infarct apparent diffusion coefficient (ADC), infarct fractional anisotropy (FA), and ALPS index of both hemispheres. Interhemispheric differences in ALPS index (infarct side vs. contralateral normal side) were assessed with a paired t-test in all patients. ALPS index was normalized by calculating ALPS ratios (right-to-left and left-to-right) for comparisons between patients and normal subjects. Comparisons of ALPS ratios between patients and normal subjects were performed using analysis of covariance with adjustments for age and sex. Linear regression analyses were performed to identify factors associated with the ALPS index.Results: In patients, the mean ALPS index ipsilateral to infarct was 1.162 ± 0.126, significantly lower (P < 0.001) than that of the contralateral side (1.335 ± 0.160). The right-to-left ALPS index ratio of patients with right cerebral infarct was 0.84 ± 0.08, significantly lower (P < 0.001) than that of normal subjects (0.95 ± 0.07). The left-to-right ALPS ratio of patients with left cerebral infarct was 0.92 ± 0.09, significantly (P < 0.001) lower than that of normal subjects (1.05 ± 0.08). On multiple linear regression analysis, time since stroke onset (β = 0.794, P < 0.001) was the only factor associated with the ALPS index.Conclusion: The ALPS index showed lower values in ischemic stroke suggesting impaired glymphatic function. Following initial impairment, the ALPS index increased with the time since stroke onset, which is suggestive of glymphatic function recovery.

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“…The ALPS index, recently proposed by Taoka et al, is another quantitative diffusion metric derived from DTI ( 22 ). It estimates the diffusivity along the perivascular spaces of medullary veins and has been used as a noninvasive quantitative marker to assess human glymphatic activity in clinical conditions including Alzheimer’s disease ( 22 , 23 ), normal pressure hydrocephalus ( 24 , 25 ), Parkinson disease ( 26 , 27 ), age-related iron deposition ( 28 ), diabetic cognitive impairment ( 29 ), and meningioma-associated brain edema ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

Peritumoral Brain Edema in Metastases May Be Related to Glymphatic Dysfunction

2021

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ObjectivesThe proliferation of microvessels with increased permeability is thought to be the cause of peritumoral brain edema (PTBE) in metastases. The contribution of the glymphatic system to the formation of PTBE in brain metastases remains unexplored. We aimed to investigate if the PTBE volume of brain metastases is related to glymphatic dysfunction.Materials and MethodsA total of 56 patients with brain metastases who had preoperative dynamic susceptibility contrast-enhanced perfusion-weighted imaging for calculation of tumor cerebral blood volume (CBV) and diffusion tensor imaging for calculations of tumor apparent diffusion coefficient (ADC), tumor fractional anisotropy (FA), and analysis along perivascular space (ALPS) index were analyzed. The volumes of PTBE, whole tumor, enhancing tumor, and necrotic and hemorrhagic portions were manually measured. Additional information collected for each patient included age, sex, primary cancer, metastasis location and number, and the presence of concurrent infratentorial tumors. Linear regression analyses were performed to identify factors associated with PTBE volume.ResultsAmong 56 patients, 45 had solitary metastasis, 24 had right cerebral metastasis, 21 had left cerebral metastasis, 11 had bilateral cerebral metastases, and 11 had concurrent infratentorial metastases. On univariable linear regression analysis, PTBE volume correlated with whole tumor volume (β = -0.348, P = 0.009), hemorrhagic portion volume (β = -0.327, P = 0.014), tumor ADC (β = 0.530, P <.001), and ALPS index (β = -0.750, P <.001). The associations of PTBE volume with age, sex, tumor location, number of tumors, concurrent infratentorial tumor, enhancing tumor volume, necrotic portion volume, tumor FA, and tumor CBV were not significant. On multivariable linear regression analysis, tumor ADC (β = 0.303; P = 0.004) and ALPS index (β = -0.624; P < 0.001) were the two independent factors associated with PTBE volume.ConclusionMetastases with higher tumor ADC and lower ALPS index were associated with larger peritumoral brain edema volumes. The higher tumor ADC may be related to increased periarterial water influx into the tumor interstitium, while the lower ALPS index may indicate insufficient fluid clearance. The changes in both tumor ADC and ALPS index may imply glymphatic dysfunction, which is, at least, partially responsible for peritumoral brain edema formation.

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Diffusion along perivascular spaces reveals evidence supportive of glymphatic function impairment in Parkinson disease

Cited by 90 publications

References 16 publications

Diffusion Tensor Imaging Along the Perivascular Space Index in Different Stages of Parkinson’s Disease

Diffusion Tensor Imaging Along the Perivascular Space Index in Different Stages of Parkinson’s Disease

Glymphatic Dysfunction in Patients With Ischemic Stroke

Peritumoral Brain Edema in Metastases May Be Related to Glymphatic Dysfunction

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