Exploring the relationship between motor impairment, vascular burden and cognition in Parkinson’s disease

Stojković, Tanja; Stefanova, Elka; Soldatović, Ivan; Marković, Vladana; Stanković, Iva; Petrović, Igor; Galantucci, Sebastiano; Filippi, Massimo; Kostić, Vladimir

doi:10.1007/s00415-018-8838-3

Cited by 31 publications

(33 citation statements)

References 40 publications

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“…Similar to the majority of previous studies which report no disease-specific differences in WMH loads in PD patients and agematched normal controls, we did not find a significant difference in WMH burden between controls and PD patients 16,18,38,39 . However, increase in WMH burden was associated with greater cognitive decline and motor and gait deficits, as previously reported in the literature 7,8,[16][17][18][19][20][21] (Figures 3.a, 5.a, and 6.a, respectively).…”

Section: Discussionsupporting

confidence: 85%

“…Given that some of the symptoms associated with WMHs in non-PD individuals overlap with PD features, one might hypothesize that coexistence of WMHs in PD patients would lead to even greater cognitive and motor deficits. However, WMH associations with cognitive and motor symptoms are less well established and consistent in PD, although some recent studies report such relationships in both de novo 16 and later stage PD patients 7,8,[17][18][19][20][21] .…”

Section: Introductionmentioning

confidence: 96%

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Cognitive and Motor Correlates of Grey and White Matter Pathology in Parkinson’s Disease

Dadar

Gee

Shuaib

et al. 2020

Preprint

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Introduction: Previous studies have found associations between grey matter atrophy and white matter hyperintensities (WMH) of vascular origin with cognitive and motor deficits in Parkinson's disease (PD).Here we investigate these relationships in a sample of PD patients and age-matched healthy controls.Methods: Data included 50 PD patients and 45 age-matched controls with T1-weighted and FLAIR scans at baseline, 18-months, and 36-months follow-up. Deformation-based morphometry was used to measure grey matter atrophy. SNIPE (Scoring by Nonlocal Image Patch Estimator) was used to measure Alzheimer's disease-like textural patterns in the hippocampi. WMHs were segmented using T1-weighted and FLAIR images. The relationship between MRI features and clinical scores was assessed using mixed-effects models. The motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRSIII), number of steps in a walking trial, and Dementia Rating Scale (DRS) were used respectively as measures of motor function, gait, and cognition.Results: Substantia nigra atrophy was significantly associated with motor deficits, with a greater impact in PDs (p<0.05). Hippocampal SNIPE scores were associated with cognitve decline in both PD and controls (p<0.01). WMH burden was significantly associated with cognitive decline and increased motor deficits in the PD group, and gait deficits in both PD and controls (p<0.03). Conclusion:While substantia nigra atrophy and WMH burden were significantly associated with additional motor deficits, WMH burden and hippocampal atrophy were associated with cognitive deficits in PD patients. These results suggest an additive contribution of both grey and white matter damage to the motor and cognitive deficits in PD.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 96%

Cognitive and Motor Correlates of Grey and White Matter Pathology in Parkinson’s Disease

Dadar

Gee

Shuaib

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…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%

“…Of interest to our study, white matter hyperintensities (WMHs) are areas of increased signal on T2weighted (T2w) magnetic resonance imaging (MRI) sequences, commonly observed in the aging population due to an interplay of ischemic, inflammatory, and protein deposition processes 15,16 . In addition to cognitive impairment and executive dysfunction, WMHs have been associated with rigidity and gait impairment in individuals with 7,[17][18][19][20][21][22][23] and without PD [24][25][26][27][28][29][30] . Interestingly, amyloid β deposition has further been linked to an increase in the WMH burden through acceleration of processes such as neuroinflammation, reactive oxygen species production, and oxidative stress [31][32][33][34][35] .…”

Section: Introductionmentioning

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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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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“…Given that cognitive impairment represents a frequent condition even in de novo PD subjects in early stages [8,9], the need to define whether VRFs represent a modifiable risk factor for slowing down or even prevent cognitive decline is urgent. Nevertheless, to date only few studies, three cross-sectional and three longitudinal, have investigated the effects of VRFs on PD-MCI and PDD occurrence according to the Movement Disorder Society (MDS) level II diagnostic criteria for PD-MCI [10,11], reporting inconclusive results [7,[12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Vascular risk factors, white matter lesions and cognitive impairment in Parkinson’s disease: the PACOS longitudinal study

et al. 2020

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Background Vascular risk factors (VRFs) may be associated with cognitive decline in early Parkinson's disease (PD) but results are inconclusive. The identification of modifiable risk factors is relevant for prevention and treatment. Methods Parkinson's disease (PD) patients of the PACOS cohort who underwent a baseline and follow-up neuropsychological evaluation were enrolled in the study. PD with Mild Cognitive Impairment (MCI) and dementia (PDD) were diagnosed according to the MDS criteria. A Baseline 1.5 T brain MRI was used to calculate the white matter lesions (WMLs) burden using the Wahlund visual scale. Laboratory data, presence of hypertension, diabetes and use of anti-hypertensive drugs were collected and the Framingham Risk (FR) score was calculated. VRFs predicting PD-MCI and PDD were evaluated using Cox proportional hazard regression model. Results Out of 139 enrolled patients, 84 (60.4%) were classified as normal cognition (NC) and 55 (39.6%) as MCI at baseline. At follow-up 28 (33.3%) PD-NC developed MCI and 4 (4.8%) PDD (follow-up time 23.5 ± 10.3 months). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD. At multivariate analysis among PD-NC a systolic blood pressure (SBP) > 140 mmHg was the stronger predictor of MCI (adjHR 4.04; 95% CI 1.41-11.3) while the presence of MCI at baseline (adj HR 7.55; 95% CI 1.76-32.3) and a severe WMLs burden (adj HR 2.80; 95% CI 0.86-9.04) were the strongest predictors of PDD, even if this latter association has a trend towards significance. Conclusion Hypertension represents the most important modifiable risk factor for PD-MCI in the PACOS cohort, increasing the risk of about four times.

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Exploring the relationship between motor impairment, vascular burden and cognition in Parkinson’s disease

Abstract: Cognitive disorders in PD are associated with more severe, predominantly axial motor deficits and increased, but partly modifiable vascular burden, thus opening a possibility for development of preventive strategies in PD.

Cited by 31 publications

References 40 publications

Cognitive and Motor Correlates of Grey and White Matter Pathology in Parkinson’s Disease

Cognitive and Motor Correlates of Grey and White Matter Pathology in Parkinson’s Disease

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

Vascular risk factors, white matter lesions and cognitive impairment in Parkinson’s disease: the PACOS longitudinal study

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