Areas of white matter hyperintensities and motor symptoms of Parkinson disease

Lee, Yoonju; Ko, Ji Wool; Choi, Ye Eun; Oh, Jungsu S.; Kim, Jae Seung; Sunwoo, Mun Kyung; Yoon, Jung Han; Kang, Suk Yun; Hong, Jin Yong

doi:10.1212/wnl.0000000000009890

Cited by 28 publications

(24 citation statements)

References 36 publications

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“…The relationship between striatal DAT levels, amyloid β and FOG in PD patients has been previously shown, both in PPMI as well as other datasets 3,6,8,9,13,14,51,52 . Regarding the SN, multiple recent studies have shown associations between free-water as an indirect measure of dopaminergic degeneration within the SN and higher Hoehn and Yahr stage, MDS-UPDRS III scores, and posture and gait in PD patients [53][54][55][56] .…”

Section: Discussionmentioning

confidence: 71%

“…In the current sample, SN DBM was associated with future FOG, further demonstrating the value of assessing SN DBM as a T1w-based marker of PD pathology in future studies. WMH burden is associated with gait deficits both in the aging population in general and in PD patients specifically 7,17,[20][21][22]51,52 . Given that WMH load is also associated with CSF amyloid β levels 31,32,57,35 and they both impact gait in PD, we hypothesized that they might impact future FOG through the same pathway.…”

Section: Discussionmentioning

confidence: 99%

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Amyloid ß Impacts Future Freezing of Gait in Parkinson’s Disease Via White Matter Hyperintensities

Dadar

Duchesne

Camicioli

2020

Preprint

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Background: Freezing of gait (FOG) is a common symptom in Parkinsons Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid β deposition. However, there is a paucity of research on the concurrent impact of white matter damage. Objectives: To assess the inter-relationships between these different co-morbidities, their impact on future FOG and whether they act independently of each other. Methods: We used baseline MRI and longitudinal gait data from the Parkinson's Progression Markers Initiative (PPMI). We used deformation based morphometry (DBM) from T1-weighted MRI to measure SN atrophy, and segmentation of white matter hyperintensities (WMH) as a measure of WM pathological load. Putamen and caudate DAT levels from SPECT as well as cerebrospinal fluid (CSF) amyloid β were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid β on future FOG. Results: SN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid β levels were significantly different between PD patients with and without future FOG (p < 0.008). Mediation analysis demonstrated an effect of CSF amyloid β levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels. Conclusions: Amyloid β might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Amyloid ß Impacts Future Freezing of Gait in Parkinson’s Disease Via White Matter Hyperintensities

Dadar

Duchesne

Camicioli

2020

Preprint

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“…CSVD has been shown to contribute to motor and cognitive functions in PD (Linortner et al, 2020). Previous work has also demonstrated that WMH is correlated with motor dysfunction and several non-motor symptoms in PD (Lee et al, 2018(Lee et al, , 2020Huang et al, 2020). However, other CSVD markers have received little attention.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the total CSVD burden, WMH has been related to motor symptoms in PD, especially bradykinesia and axial symptoms Lee et al, 2020;Jeong et al, 2021). Other studies also indicated that WMH correlated with motor subtype and gait in patients with PD Al-Bachari et al, 2017;Toda et al, 2019;Wan et al, 2019).…”

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confidence: 99%

Total Cerebral Small Vessel Score Association With Hoehn and Yahr Stage in Parkinson’s Disease

et al. 2021

Front. Aging Neurosci.

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Background: This study aimed to evaluate the total cerebral small vessel disease (CSVD) score in patients with Parkinson’s disease (PD) at different stages and related factors.Methods: A 100 and seven patients with idiopathic PD and 62 normal controls (NCs) who underwent brain magnetic resonance imaging (MRI) were enrolled. PD patients were divided into two groups: early PD [(Hoehn and Yahr (H&Y) 1–1.5, n = 36)] and advanced PD (H&Y 2–4, n = 71) groups. We calculated the total CSVD score for each participant based on lacunes, high-grade white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs). Differences in total CSVD score between the PD and NCs and between the two subgroups were compared. In addition, a multivariate logistic regression analysis was conducted to investigate the association between CSVD markers and clinical variables in PD.Results: Lacunes were found in 9.3% of patients with PD, periventricular WMH (PVWMH) in 89.7%, deep WMH (DWMH) in 81.3%, EPVS in 85%, and CMBs in 2.8%. Compared with NCs, patients with PD showed higher PVWMH and DWMH scores. Advanced PD patients exhibited greater PVWMH (P = 0.041), DWMH (P = 0.046), and total CSVD score (P = 0.044) than the early PD group. After adjusting for multiple variables, higher H&Y stage was independently correlated with increased total CSVD score (OR = 2.667, 95% CI 1.154–2.266) and PVWMH score (OR = 2.237, 95% CI 1.084–1.696).Conclusions: CSVD may play a critical role in patients with PD. The total CSVD score is a potential neuroimaging marker for monitoring the progression of PD.

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“…In mouse model of CCH, changes in white matter have been shown to be closely associated with cognitive deficits. Cognitive impairment is usually measured using MWMT, OFT, and FST (4,5).…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide Improves Cognitive Function in Mice With Chronic Cerebral Hypoperfusion

et al. 2021

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Normal brain function requires steady blood supply to maintain stable energy state. When blood supply to the brain becomes suboptimal for a long period of time, chronic cerebral hypoperfusion (CCH) and a variety of brain changes may occur. CCH causes white matter injury and cognitive impairment. The present study investigated the effect of nicotinamide (NAM) on CCH-induced cognitive impairment and white matter damage in mice. Male C57Bl/6J mice aged 10–12 weeks (mean age = 11 ± 1 weeks) and weighing 24 - 29 g (mean weight = 26.5 ± 2.5 g) were randomly assigned to three groups (eight mice/group): sham group, CCH group and NAM group. Chronic cerebral hypoperfusion (CCH) was induced using standard methods. The treatment group mice received intraperitoneal injection of NAM at a dose of 200 mg/kg body weight (bwt) daily for 30 days. Learning, memory, anxiety, and depression-like behaviors were measured using Morris water maze test (MWMT), open field test (OFT), sucrose preference test (SPT), and forced swim test (FST), respectively. White matter damage and remodeling were determined via histological/ immunohistochemical analyses, and western blotting, respectively. The results showed that the time spent in target quadrant, number of crossings and escape latency were significantly lower in CCH group than in sham group, but they were significantly increased by NAM (p < 0.05). Mice in NAM group moved significantly faster and covered longer distances, when compared with those in CCH group (p < 0.05). The percentage of time spent in open arms and the number of entries to the open arms were significantly lower in CCH group than in NAM group (p < 0.05). Moreover, anhedonia and histologic scores (index of myelin injury) were significantly higher in CCH group than in sham group, but they were significantly reduced by NAM (p < 0.05). The results of immunohistochemical staining and Western blotting showed that the protein expressions of 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) and synaptophysin were significantly downregulated in CCH group, relative to sham group, but they were significantly upregulated by NAM (p < 0.05). These results indicate that NAM improves cognitive function in mice with CCH.

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Areas of white matter hyperintensities and motor symptoms of Parkinson disease

Cited by 28 publications

References 36 publications

Amyloid ß Impacts Future Freezing of Gait in Parkinson’s Disease Via White Matter Hyperintensities

Amyloid ß Impacts Future Freezing of Gait in Parkinson’s Disease Via White Matter Hyperintensities

Total Cerebral Small Vessel Score Association With Hoehn and Yahr Stage in Parkinson’s Disease

Nicotinamide Improves Cognitive Function in Mice With Chronic Cerebral Hypoperfusion

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