White Matter Changes Correlates of Peripheral Neuroinflammation in Patients with Parkinson’s Disease

Haghshomar, Maryam; Rahmani, Farzaneh; Aarabi, Mohammad Hadi; Shahjouei, Shima; Sobhani, Soheila; Rahmani, Maryam

doi:10.1016/j.neuroscience.2017.10.050

Cited by 30 publications

(19 citation statements)

References 44 publications

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“…As indicated above, previously published studies has investigated connectometry differences in other neurological diseases [24][25][26][27][28][29][30][31][32][33][34], adopting SDF as biomarker of investigation. SDF is a densitybased measurement of diffusion at different orientations and it measures the density of diffusing water, differently from other diffusivity measurements such as Fractional Anisotropy (FA), Apparent Diffusion Coefficient (ADC) and Radial Diffusivity.…”

Section: Discussionmentioning

confidence: 99%

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Connectometry evaluation in patients undergoing carotid endarterectomy: an exploratory study

Porcu

Craboledda

Garofalo

et al. 2018

Brain Imaging and Behavior

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Introduction: Investigating on brain local connectivity changes following Carotid Endarterectomy (CEA) by connectometry. Methods: In this exploratory study, seventeen subjects (15 males and 2 females, mean age 74.1 years) who underwent CEA, were prospectively recruited. Within one week before the CEA, each patient performed, in the same day, a cognitive evaluation with a Mini Mental State Examination (MMSE) and a Magnetic Resonance (MR) exam that included a DTI sequence for the connectometry analysis. The same cognitive test and MR protocol were performed on follow-up in a period between 3-6 months after CEA. The MMSE scores were analyzed using T-Student test. The connectometry analysis was performed using a multiple regression model in order to consider the effect of CEA, choosing three different T-score threshold values (1, 2 and 3), and results were considered statistically valid when p-value adjusted for False Discovery Rate (p-FDR) < 0.05. Results: Comparison of pre-CEA and post-CEA MMSE scores showed improvement of MMSE scores after CEA (p-value = 0.0001). Connectometry analysis revealed no areas of statistically significant increased connectivity related to CEA for T-threshold value = 1 and 2, whereas for Tthreshold value = 3 the analysis revealed statistically significant increased connectivity after CEA (p-FDR = 0.0106667) in both cerebellar hemispheres and corpus callosum. Conclusion: The results suggest that CEA procedure is associated with both improvements of cognitive performances and changes in both interhemispheric local connectivity through corpus callosum and in cerebellum.

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Section: Discussionmentioning

confidence: 99%

“…The spin distribution function (SDF) is the parameter used for the analysis [23]. This method has been already used for example for the study of Parkinson disease [24][25][26][27][28][29][30], mood disorders [31,32], multiple sclerosis [33] and amyotrophic lateral sclerosis [34].…”

Section: Introductionmentioning

confidence: 99%

Connectometry evaluation in patients undergoing carotid endarterectomy: an exploratory study

Porcu

Craboledda

Garofalo

et al. 2018

Brain Imaging and Behavior

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“…Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD). It is proposed that progressive damage of α-synuclein inclusions to the neural cells by causing neuroinflammation and oxidative imbalance plays the central role in PD pathology ( 1 – 4 ). In addition, the existence of extracellular plaques of amyloid-beta and intracellular aggregation of abnormal tau proteins, the main pathological insults in AD, are as well documented in PD with a great impact on the development of cognitive decline and dementia ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Serum Insulin-Like Growth Factor-1 in Parkinson's Disease; Study of Cerebrospinal Fluid Biomarkers and White Matter Microstructure

et al. 2018

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Background: Growing evidence shows that impaired signaling of Insulin-like Growth Factor-1 (IGF-1) is associated with neurodegenerative disorders, such as Parkinson's disease (PD). However, there is still controversy regarding its proinflammatory or neuroprotective function. In an attempt to elucidate the contribution of IGF-1 in PD, we aimed to discover the relation between serum IGF-1 levels in drug-naïve early PD patients and cerebrospinal fluid (CSF) biomarkers as well as microstructural changes in brain white matter.Methods: The association between quartiles of serum IGF-1 levels and CSF biomarkers (α-synuclein, dopamine, amyloid-β1−42, total tau, and phosphorylated tau) was investigated using adjusted regression models in 404 drug-naïve early PD patients with only mild motor manifestations and 188 age- and sex-matched healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). By using region of interest analysis and connectometry approach, we tracked the white matter microstructural integrity and diffusivity patterns in a subgroup of study participants with available diffusion MRI data to investigate the association between subcomponents of neural pathways with serum IGF-1 levels.Results: PD patients had higher levels of IGF-1 compared to HC, although not statistically significant (mean difference: 3.60, P = 0.44). However, after adjustment for possible confounders and correction for False Discovery Rate (FDR), IGF-1 was negatively correlated with CSF α-synuclein, total and phosphorylated tau levels only in PD subjects. The imaging analysis proved a significant negative correlation (FDR corrected P-value = 0.013) between continuous levels of serum IGF-1 in patients with PD and the connectivity, but not integrity, in following fibers while controlling for age, sex, body mass index, depressive symptoms, education years, cognitive status and disease duration: middle cerebellar peduncle, cingulum, genu and splenium of the corpus callosum. No significant association was found between brain white matter microstructral measures or CSF markers of healthy controls and levels of IGF-1.Conclusion: Altered connectivity in specific white matter structures, mainly involved in cognitive and motor deterioration, in association with higher serum IGF-1 levels might propose IGF-1 as a potential associate of worse outcome in response to higher burden of α-synucleinopathy and tauopathy in PD.

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“…Beyond MS, neuroinflammation has been shown to be relevant for a number of brain pathologies which would benefit from non-invasive monitoring tools. For example, a diffusion MRI study reports an interesting correlation between white matter microstructure and blood markers of neuroinflammation, such as the neutrophil-to-lymphocyte ratio, in early Parkinson's disease patients, reopening the interesting discussion around the contribution of neuroinflammation to the pathogenesis of this disease (Haghshomar et al, 2017). Also investigating myelin integrity in Huntington's patients, using a multi-contrast MRI approach (Bourbon-Teles et al, 2017), other authors were able to unveil damaged WM pathways of the basal ganglia and motor systems in early stages of the disease, and discuss the possible role of myelin breakdown in triggering neuroinflammation.…”

mentioning

confidence: 99%

Non-invasive MRI windows to neuroinflammation

Santis

Canals

2019

Neuroscience

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White Matter Changes Correlates of Peripheral Neuroinflammation in Patients with Parkinson’s Disease

Cited by 30 publications

References 44 publications

Connectometry evaluation in patients undergoing carotid endarterectomy: an exploratory study

Connectometry evaluation in patients undergoing carotid endarterectomy: an exploratory study

Serum Insulin-Like Growth Factor-1 in Parkinson's Disease; Study of Cerebrospinal Fluid Biomarkers and White Matter Microstructure

Non-invasive MRI windows to neuroinflammation

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