Diffusion along perivascular spaces provides evidence interlinking compromised glymphatic function with aging in Parkinson's disease

Cai, Xin; Chen, Zhenzhen; He, Chentao; Zhang, Haining; Nie, Kun; Qiu, Yihui; Wang, Limin; Jing, Ping; Zhang, Yuhu

doi:10.1111/cns.13984

Cited by 35 publications

(26 citation statements)

References 39 publications

(122 reference statements)

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“…The DTI‐ALPS index and age/duration of epilepsy showed significant correlations in the present study. The decline in glymphatic system function with age was consistent with the results of several previous studies [42, 43]. With regard to the glymphatic system, sleep quality shows a notable decline with normal aging.…”

Section: Discussionsupporting

confidence: 91%

Anti‐seizure medication response and the glymphatic system in patients with focal epilepsy

Kim,

Lee

et al. 2023

Euro J of Neurology

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Background and purposeWe aimed to evaluate (i) glymphatic system function in patients with focal epilepsy in comparison with healthy controls, and (ii) the association between anti‐seizure medication (ASM) response and glymphatic system function by using diffusion tensor image analysis along the perivascular space (DTI‐ALPS).MethodsWe retrospectively enrolled 100 patients with focal epilepsy who had normal brain magnetic resonance imaging (MRI) findings, and classified them as “poor” or “good” ASM responders according to their seizure control at the time of brain MRI. We also included 79 age‐ and sex‐matched healthy controls. All patients and healthy controls underwent conventional brain MRI and diffusion tensor imaging. The DTI‐ALPS index was calculated using the DSI studio program.ResultsOf the 100 patients with focal epilepsy, 38 and 62 were poor and good ASM responders, respectively. The DTI‐ALPS index differed significantly between patients with focal epilepsy and healthy controls and was significantly lower in patients with focal epilepsy (1.55 vs. 1.70; p < 0.001). The DTI‐ALPS index also differed significantly according to ASM response and was lower in poor ASM responders (1.48 vs. 1.59; p = 0.047). Furthermore, the DTI‐ALPS index was negatively correlated with age (r = −0.234, p = 0.019) and duration of epilepsy (r = −0.240, p = 0.016) in patients with focal epilepsy.ConclusionOur study is the first to identify, in focal epilepsy patients, a greater reduction in glymphatic system function among poor ASM responders compared to good responders. To confirm our results, further prospective multicenter studies with large sample sizes are needed.

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Section: Discussionsupporting

confidence: 91%

Anti‐seizure medication response and the glymphatic system in patients with focal epilepsy

Kim,

Lee

et al. 2023

Euro J of Neurology

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“…Additionally, we conducted correlation analysis by treating the ALPS index as a continuous variable to investigate the interlink between baseline glymphatic neuroimaging indicators and the longitudinal changes in clinical PD symptoms, which further validated the predictive role of the glymphatic system. Still, ALPS index was an indirect and regional biomarker measuring glymphatic activity in the basal ganglion area 13 . As such, we should interpret the association between glymphatic function and longitudinal changes in clinical PD symptoms cautiously, and whether glymphatic dysfunction involved in the progression requires further investigation.…”

Section: Discussionmentioning

confidence: 98%

“…Still, ALPS index was an indirect and regional biomarker measuring glymphatic activity in the basal ganglion area. 13 As such, we should interpret the association between glymphatic function and longitudinal changes in clinical PD symptoms cautiously, and whether glymphatic dysfunction involved in the progression requires further investigation. However, recent study showed that the ALPS index was highly correlated with classical glymphatic function measured by glymphatic MRI, 14 and it has widely been used as an imaging indicator of whole-brain glymphatic function in clinical studies.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a noninvasive method called diffusion tensor image analysis along the perivascular space (DTI‐ALPS) has been proposed to evaluate glymphatic function based on the diffusivity of water molecules using diffusion tensor imaging (DTI) 12 . The ALPS index has been found to be significantly related to the classically detected glymphatic clearance function (contrast‐enhanced MRI), and as such has also been applied in the study of PD 13 and cerebral small vessel disease 14 to evaluate glymphatic function.…”

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confidence: 99%

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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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“…Recently, diffusion tensor image analysis along the perivascular space (DTI-ALPS) has emerged as an alternative non-invasive method for evaluating the glymphatic function in human brain ( 5 , 16 ). Several studies have reported the ability of the DTI-ALPS method to characterize glymphatic function in PD patients, and the lower ALPS index may reflect impairment of the glymphatic system ( 17 - 19 ).…”

Section: Introductionmentioning

confidence: 99%

Association between body mass index and glymphatic function using diffusion tensor image-along the perivascular space (DTI-ALPS) in patients with Parkinson’s disease

Tian,

Hong,

Luo

et al. 2024

Quant Imaging Med Surg

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Background Obesity is considered a risk factor for the development of several neurodegenerative diseases, including Parkinson’s disease (PD). Recent studies have revealed that glymphatic function is compromised in PD patients. This study aims to investigate the impact of different body mass index (BMI) statuses on glymphatic system function in PD patients using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Methods This study used a cross-sectional study design. A total of 145 PD patients were retrospectively enrolled in Parkinson’s Progression Markers Initiative (PPMI) from 2010–2013. Eligibility criteria included diagnosis of PD based on PPMI criteria. Diffusion tensor image (DTI) scans (diffusion gradient =64, b-value =1,000 s/mm 2 , slice thickness =2 mm) were acquired, and the analysis along the perivascular space (ALPS) index of each subject was calculated. The patient cohort was categorized into three groups based on BMI: normal weight (N=49), overweight (N=69), and obese (N=27). The difference in ALPS index among groups was performed by one-way analysis of variance (ANOVA). Partial correlation analysis was used to observe the relationship between ALPS index, BMI status, and demographics. Spearman’s rank correlation coefficient and multivariable linear regression analyses were used to identify factors associated with ALPS index. Results PD patients with higher BMI exhibited a reduced ALPS index (normal weight > overweight > obese), and the ALPS index for patients with obesity was statistically significantly lower than that for patients with normal weight (P<0.001). After adjusting for age, sex, years of education, handedness, and disease duration, a significant negative correlation between the ALPS index and BMI was observed in the PD patients (R=−0.275, P<0.001). Furthermore, a negative correlation between the ALPS index and the severity of motor symptoms was identified in the subgroup of overweight (R=−0.318, P=0.01), rather than in the normal weight and obese groups. Conclusions High BMI has a negative impact on the glymphatic function in PD patients, suggesting that weight control may have clinical relevance in the management of PD patients.

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Diffusion along perivascular spaces provides evidence interlinking compromised glymphatic function with aging in Parkinson's disease

Cited by 35 publications

References 39 publications

Anti‐seizure medication response and the glymphatic system in patients with focal epilepsy

Anti‐seizure medication response and the glymphatic system in patients with focal epilepsy

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

Association between body mass index and glymphatic function using diffusion tensor image-along the perivascular space (DTI-ALPS) in patients with Parkinson’s disease

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