Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

Li, Yifei; Zhou, Ying; Zhong, Wansi; Zhu, Xiaoyan; Chen, Yuping; Zhang, Kemeng; He, Yaode; Luo, Zhongyu; Wang, Ran; Sun, Jinwei; Lou, Min

doi:10.1002/ana.26648

Cited by 20 publications

(14 citation statements)

References 51 publications

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“…Our finding of the association between CSVD and glymphatic markers in the AD continuum was in line with previous studies focusing on CSVD patients [ 13 , 18 , 21 ]. Brain-wide network of perivascular pathways made up glymphatic system [ 49 ], so the damage of small cerebral vessels was closely correlated with glymphatic function.…”

Section: Discussionsupporting

confidence: 93%

“…DTI-ALPS assesses diffusivity along deep medullary veins and is suggested as a marker for evaluating glymphatic clearance function [ 17 ]. Choroid plexus volume plays a crucial role in the production of cerebrospinal fluid (CSF) and may act as a driving force for the glymphatic system [ 13 ]. Enlarged PVS observed on MRI is mostly situated around arterioles, which might cause hydrodynamic changes in CSF inflow and exchange with parenchymal fluid [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Hypertensive rats, the most common model of CSVD, showed suppressed glymphatic function [ 9 ], and the multiple microinfarct murine model also demonstrated global glymphatic pathway impairment [ 11 ]. In vivo studies using imaging markers for CSVD, mostly white matter hyperintensities (WMH) burden, found its spatial correlation with enlarged PVS and other non-invasive glymphatic markers [ 12 , 13 ]. The effect of AD pathologies and CSVD on glymphatic function is separately proved in AD and CSVD models, respectively.…”

Section: Introductionmentioning

confidence: 99%

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The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer’s disease continuum participants

Hong,

Luo

et al. 2024

Alz Res Therapy

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Background Glymphatic dysfunction is a crucial pathway for dementia. Alzheimer’s disease (AD) pathologies co-existing with cerebral small vessel disease (CSVD) is the most common pathogenesis for dementia. We hypothesize that AD pathologies and CSVD could be associated with glymphatic dysfunction, contributing to cognitive impairment. Method Participants completed with amyloid PET, diffusion tensor imaging (DTI), and T2 fluid-attenuated inversion-recovery (FLAIR) sequences were included from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). White matter hyperintensities (WMH), the most common CSVD marker, was evaluated from T2FLAIR images and represented the burden of CSVD. Amyloid PET was used to assess Aβ aggregation in the brain. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, the burden of enlarged perivascular spaces (PVS), and choroid plexus volume to reflect glymphatic function. The relationships between WMH burden/Aβ aggregation and these glymphatic markers as well as the correlations between glymphatic markers and cognitive function were investigated. Furthermore, we conducted mediation analyses to explore the potential mediating effects of glymphatic markers in the relationship between WMH burden/Aβ aggregation and cognition. Results One hundred and thirty-three participants along the AD continuum were included, consisting of 40 CN − , 48 CN + , 26 MCI + , and 19 AD + participants. Our findings revealed that there were negative associations between whole-brain Aβ aggregation (r = − 0.249, p = 0.022) and WMH burden (r = − 0.458, p < 0.001) with DTI-ALPS. Additionally, Aβ aggregation (r = 0.223, p = 0.041) and WMH burden (r = 0.294, p = 0.006) were both positively associated with choroid plexus volume. However, we did not observe significant correlations with PVS enlargement severity. DTI-ALPS was positively associated with memory (r = 0.470, FDR-p < 0.001), executive function (r = 0.358, FDR-p = 0.001), visual-spatial (r = 0.223, FDR-p < 0.040), and language (r = 0.419, FDR-p < 0.001). Conversely, choroid plexus volume showed negative correlations with memory (r = − 0.315, FDR-p = 0.007), executive function (r = − 0.321, FDR-p = 0.007), visual-spatial (r = − 0.233, FDR-p = 0.031), and language (r = − 0.261, FDR-p = 0.021). There were no significant correlations between PVS enlargement severity and cognitive performance. In the mediation analysis, we found that DTI-ALPS acted as a mediator in the relationship between WMH burden/Aβ accumulation and memory and language performances. Conclusion Our study provided evidence that both AD pathology (Aβ) and CSVD were associated with glymphatic dysfunction, which is further related to cognitive impairment. These results may provide a theoretical basis for new targets for treating AD.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer’s disease continuum participants

Hong,

Luo

et al. 2024

Alz Res Therapy

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“…In addition, a recent neuroimaging study showed that CP enlargement was closely associated with glymphatic dysfunction [10]. Regarding the role of the glymphatic system in PD [7–9] and the relationship between CPV and glymphatic function, we can infer that CPV may play a role in the pathogenesis of PD.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, a recent neuroimaging study showed that CP enlargement was closely associated with glymphatic dysfunction [10].…”

Section: Introductionmentioning

confidence: 99%

Association between choroid plexus volume and cognition in Parkinson disease

Jeong

Sunwoo

et al. 2023

Euro J of Neurology

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Background and purposeThe choroid plexus (CP) clears harmful metabolites from the central nervous system as part of the glymphatic system. We investigated the association of CP volume (CPV) with baseline and longitudinal cognitive decline in patients with Parkinson disease (PD).MethodsWe retrospectively reviewed the medical records of 240 patients with newly diagnosed PD who had undergone detailed neuropsychological tests and high‐resolution T1‐weighted structural magnetic resonance imaging during the initial assessment. The CPV of each patient was automatically segmented, and the intracranial volume ratio was used in subsequent analyses. The relationship between CPV and baseline composite scores of each cognitive domain was assessed using multivariate linear regression analyses. A Cox proportional hazards model was used to compare the risk of dementia conversion with CPV.ResultsCPV negatively correlated with composite scores of the frontal/executive function domain (β = −0.375, p = 0.002) after adjusting for age, sex, years of education, and parkinsonian symptom duration. The Cox regression model revealed that a larger CPV was associated with a higher risk of dementia conversion (hazard ratio [HR] = 1.509, p = 0.038), which was no longer significant after adjusting for the composite scores of the frontal/executive function domain. A mediation analysis demonstrated that the effect of CPV on the risk of dementia conversion was completely mediated by frontal/executive function (direct effect: HR = 1.203, p = 0.396; indirect effect: HR = 1.400, p = 0.015).ConclusionsBaseline CPV is associated with baseline frontal/executive function, which subsequently influences dementia conversion risk in patients with PD.

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The Association of the Glymphatic Function with Parkinson's Disease Symptoms: Neuroimaging Evidence from Longitudinal and Cross‐Sectional Studies

Shi

et al. 2023

Annals of Neurology

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ObjectiveEmerging pathological evidence suggests that there is an association between glymphatic dysfunction and the progression of Parkinson's disease (PD). However, the clinical evidence of this association remains lacking.MethodsIn this study, the index for diffusion tensor image analysis along the perivascular space (ALPS index) was calculated to evaluate glymphatic function.ResultsOverall, 289 patients with PD were enrolled in the cross‐sectional study. The ALPS index was found to be negatively correlated with age, disease severity, and dyskinesia. In the longitudinal study, the information on a total of 95 PD patients with 5‐year follow‐up examinations was collected from the Parkinson's Progression Marker Initiative, 33 of which were classified into the low ALPS index group, and all others were classified into the mid‐high ALPS index group based on the first tertile of the baseline ALPS index. The results of longitudinal regression indicated that there was a significant main group effect on autonomic dysfunction, as well as on activities of daily living. In addition, the low ALPS index group had faster deterioration in MDS‐UPDRS part III and part II, Symbol Digit Modalities Test and Hopkins Verbal Learning Test. Path analysis showed that ALPS index acted as a significant mediator between tTau/ Aβ1‐42 and cognitive change in the Symbol Digit Modalities Test score at year 4 and year 5.InterpretationThe ALPS index, an neuroimaging marker of glymphatic function, is correlated with PD disease severity, motor symptoms, and autonomic function, and is predictive of faster deterioration in motor symptoms and cognitive function. Additionally, glymphatic function may mediate the pathological role of toxic protein in cognitive decline. ANN NEUROL 2023

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Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

Cited by 20 publications

References 51 publications

The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer’s disease continuum participants

The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer’s disease continuum participants

Association between choroid plexus volume and cognition in Parkinson disease

The Association of the Glymphatic Function with Parkinson's Disease Symptoms: Neuroimaging Evidence from Longitudinal and Cross‐Sectional Studies

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