"Long-term MRI findings in Ankylosing spondylitis patients treated with TNF inhibitors for a decade".

OBJECTIVE: This study aims to evaluate the active and chronic lesions in sacroiliac joints and lumbar spine over a decade of TNFi therapy in patients with AS. METHODS: The study enrolled patients with AS under treatment with a TNFi for over a decade. The patients underwent a new MRI scan of their lumbar spine and sacroiliac joint (SIJ). Two readers evaluated all images. Inflammation of SIJ (SIS), SIJ structural damage (SSS) including Fat Metaplasia, Erosions, Backfill and Ankylosis, and Spondyloarthritis Research Consortium of Canada Bone marrow edema (SPARCC) spine score were recorded. RESULTS: In the study, 15 patients were included, with 80% being male. The mean age during their first MRI was 38.1 (± 11.9) years old, and the majority (86.7%) tested positive for HLA-B27. While TNFi improved both BASDAI and BASFI scores, there was a noticeable increase in MRI acute lesions in the SIJ over time, where the median score increased from 0 (0-4) to 3 (0-10) after ten years (p = 0.028). After a decade of treatment, the median SPARCC spine score also increased from 0 (0-9) to 5 (0-16), p = 0.093. Finally, it was observed that there was a significant positive correlation between ESR and SIS erosions in cases of chronic lesions (r = 0.819, p < 0.001). CONCLUSIONS: While TNFi have significantly improved the treatment of AS, this study shows that acute lesions can still develop despite treatment. A personalized approach that adapts MRI assessment to each patient's specific requirements may help detect changes early and enable doctors to intervene promptly to prevent further damage.

Therapeutic Potential of Linearol in Combination with Radiotherapy for the Treatment of Glioblastoma In Vitro.

Glioblastoma is one of the most malignant and lethal forms of primary brain tumors in adults. Linearol, a kaurane diterpene isolated from different medicinal plants, including those of the genus Sideritis, has been found to possess significant anti-oxidant, anti-inflammatory and anti-microbial properties. In this study, we aimed to determine whether linearol could exhibit anti-glioma effects when given alone or in combination with radiotherapy in two human glioma cell lines, U87 and T98. Cell viability was examined with the Trypan Blue Exclusion assay, cell cycle distribution was tested with flow cytometry, and the synergistic effects of the combination treatment were analyzed with CompuSyn software. Linearol significantly suppressed cell proliferation and blocked cell cycle at the S phase. Furthermore, pretreatment of T98 cells with increasing linearol concentrations before exposure to 2 Gy irradiation decreased cell viability to a higher extent than linearol or radiation treatment alone, whereas in the U87 cells, an antagonistic relationship was observed between radiation and linearol. Moreover, linearol inhibited cell migration in both tested cell lines. Our results demonstrate for the first time that linearol is a promising anti-glioma agent and further studies are needed to fully understand the underlying mechanism of this effect.

Functional connectivity and microstructural changes of the brain in primary Sjögren syndrome: the relationship with depression.

BACKGROUND: Fatigue and depression are among the most common manifestations of primary Sjögren syndrome (pSS), but information is lacking on the relationship with brain function and microstructural changes. PURPOSE: To investigate microstructural changes and brain connectivity in pSS, and to evaluate their relationship with fatigue and depression. MATERIAL AND METHODS: The study included 29 patients with pSS (mean age 61.2 ± 12.1 years; disease duration 10.5 ± 5.9 years) and 28 controls (mean age 58.4 ± 9.2 years). All the patients completed the Beck's depression and Fatigue Assessment Scale questionnaires. The imaging protocol consisted of: (i) standard magnetic resonance imaging (MRI) pulse sequences (FLAIR, 3D T1W); (ii) a diffusion tensor imaging pulse sequence; and (iii) a resting state functional MRI pulse sequence. Resting state brain networks and maps of diffusion metrics were calculated and compared between patients and controls. RESULTS: Compared with the controls, the patients with pSS and depression showed increased axial, radial, and mean diffusivity and decreased fractional anisotropy; those without depression showed decreased axial diffusivity in major white matter tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, anterior thalamic radiation, inferior fronto-occipital fasciculus, cingulum, uncinate fasciculus, and forceps minor-major). Decreased brain activation in the sensorimotor network was observed in the patients with pSS compared with the controls. No correlation was found between fatigue and structural or functional changes of the brain. CONCLUSION: pSS is associated with functional connectivity abnormalities of the somatosensory cortex and microstructural abnormalities in major white matter tracts, which are more pronounced in depression.

Postpartum intracranial hypotension complicated by posterior reversible encephalopathy syndrome: a case report.

Purpose: To present an unusual case of posterior encephalopathy syndrome (PRES) preceded by intracranial hypotension.Materials and Methods: We present a case of a 27-year-old parturient with an uneventful pregnancy that shortly after labor developed a persistent headache with characteristics compatible with intracranial hypotension. The patient had undergone epidural anesthesia for caesarian section. Results: The symptomatology of intracranial hypotension was attributed to inadvertent dural puncture during epidural anesthesia. The MRI revealed multiple white matter lesions located in frontal, temporal and parietal regions of both hemispheres. The type of lesions was suggestive of PRES. Pachymeningeal enhancement was also observed. The patient was managed conservatively. The symptoms improved gradually and the imaging findings resolved completely. Conclusions: This case demonstrates the need for clinical alertness for PRES in patients with prolonged and possibly atypical symptoms of intracranial hypotension. As probable causal relationship between these disorders we propose a sympathetic over-activation as a result of cerebrospinal fluid leakage leading to vasospasm and manifestation of PRES.

Functional and structural connectivity of the brain in very preterm babies: relationship with gestational age and body and brain growth.

BACKGROUND: Structural and functional changes of the brain have been reported in premature babies. OBJECTIVE: To evaluate the relationship of functional and structural connectivity with gestational age, body growth and brain maturation in very preterm babies. MATERIALS AND METHODS: We studied 18 very preterm babies (gestational age: mean ± standard deviation, 29.7±1.7 weeks). We examined functional connectivity by multivariate pattern analysis of resting-state functional MRI data. We assessed structural connectivity by analysis of diffusion tensor imaging data and probabilistic tractography. RESULTS: The average functional connectivity of the medial orbitofrontal cortex with the rest of the brain was positively associated with gestational age (P<0.001). Fractional anisotropy of the right inferior fronto-occipital fasciculus was positively associated with head circumference at term-equivalent age. Structural connectivity of the inferior fronto-occipital fasciculus with the medial orbitofrontal cortex was positively associated with head circumference at term-equivalent age. Body weight at term-equivalent age was the only independent predictor of average structural connectivity of the medial orbitofrontal cortex with the rest of the brain (P=0.020). CONCLUSION: Structural and functional connectivity of the medial orbitofrontal cortex with the rest of the brain depend on body growth and degree of prematurity, respectively.

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes.

BACKGROUND: There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. OBJECTIVE: To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. MATERIALS AND METHODS: Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. RESULTS: Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. CONCLUSION: Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity.

Multimodal imaging evaluation of excessive daytime sleepiness in Parkinson's disease.

PURPOSE OF THE STUDY: The multimodal imaging investigation of excessive daytime sleepiness (EDS) in Parkinson's disease (PD). The role of dopaminergic treatment and other clinical parameters was also evaluated. MATERIALS AND METHODS: Seventeen non-demented PD patients with EDS (PD-EDS) and 17 PD patients without EDS were enrolled. Clinical, treatment and MRI data were acquired. Gray matter (GM) volume was examined with voxel-based morphometry, while white matter (WM) integrity was assessed with diffusion tensor imaging by means of fractional anisotropy, mean diffusivity, axial diffusivity (AD) and radial diffusivity measures. RESULTS: Increased regional GM volume was found in the PD-EDS group bilaterally in the hippocampus and parahippocampal gyri. Increased AD values were also shown in the PD-EDS group, in the left anterior thalamic radiation and the corticospinal tract and bilaterally in the superior corona radiata and the superior longitudinal fasciculus. Levodopa equivalent dose differed significantly between the groups and was the only predictor of EDS, while the only predictor of the Epworth sleepiness scale score in the PD-EDS group was the dopamine-agonist dose. Increased frequency of gamblers was also observed in the PD-EDS group. CONCLUSIONS: Regional GM increases and increased AD values in certain WM tracts were found in the PD-EDS group. The changes could result from disinhibited signaling pathways or represent compensatory changes in response to anatomical or functional deficits elsewhere. The study findings support also the contribution of the total dopaminergic load in the development of EDS, while the dose of dopamine agonists was found to predict the severity of the disorder.

Brain involvement in patients with inflammatory bowel disease: a voxel-based morphometry and diffusion tensor imaging study.

OBJECTIVES: To investigate structural brain changes in inflammatory bowel disease (IBD). METHODS: Brain magnetic resonance imaging (MRI) was performed on 18 IBD patients (aged 45.16 ± 14.71 years) and 20 aged-matched control subjects. The imaging protocol consisted of a sagittal-FLAIR, a T1-weighted high-resolution three-dimensional spoiled gradient-echo sequence, and a multisession spin-echo echo-planar diffusion-weighted sequence. Differences between patients and controls in brain volume and diffusion indices were evaluated using the voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, respectively. The presence of white-matter hyperintensities (WMHIs) was evaluated on FLAIR images. RESULTS: VBM revealed decreased grey matter (GM) volume in patients in the fusiform and the inferior temporal gyrus bilaterally, the right precentral gyrus, the right supplementary motor area, the right middle frontal gyrus and the left superior parietal gyrus (p < 0.05). TBSS showed decreased axial diffusivity (AD) in the right corticospinal tract and the right superior longitudinal fasciculus in patients compared with controls. A larger number of WMHIs was observed in patients (p < 0.05). CONCLUSIONS: Patients with IBD show an increase in WMHIs and GM atrophy, probably related to cerebral vasculitis and ischaemia. Decreased AD in major white matter tracts could be a secondary phenomenon, representing Wallerian degeneration. KEY POINTS: • There is evidence of central nervous system involvement in IBD. • Diffusion tensor imaging detects microstructural brain abnormalities in IBD. • Voxel based morphometry reveals brain atrophy in IBD.

Body growth and brain development in premature babies: an MRI study.

BACKGROUND: Prematurity and intrauterine growth restriction are associated with neurodevelopmental disabilities. OBJECTIVE: To assess the relationship between growth status and regional brain volume (rBV) and white matter microstructure in premature babies at around term-equivalent age. MATERIALS AND METHODS: Premature infants (n= 27) of gestational age (GA): 29.8 ± 2.1 weeks, with normal brain MRI scans were studied at corrected age: 41.2 ± 1.4 weeks. The infants were divided into three groups: 1) appropriate for GA at birth and at the time of MRI (AGA), 2) small for GA at birth with catch-up growth at the time of MRI (SGAa) and 3) small for GA at birth with failure of catch-up growth at the time of MRI (SGAb). The T1-weighted images were segmented into 90 rBVs using the SPM8/IBASPM and differences among groups were assessed. Fractional anisotropy (FA) was measured bilaterally in 15 fiber tracts and its relationship to GA and somatometric measurements was explored. RESULTS: Lower rBV was observed in SGAb in superior and anterior brain areas. A positive correlation was demonstrated between FA and head circumference and body weight. Body weight was the only significant predictor for FA (P< 0.05). CONCLUSION: In premature babies, catch-up growth is associated with regional brain volume catch-up at around term-equivalent age, starting from the brain areas maturing first. Body weight seems to be a strong predictor associated with WM microstructure in brain areas related to attention, language, cognition, memory and executing functioning.

Survival Outcome Prediction in Glioblastoma: Insights from MRI Radiomics.

Background: Extracting multiregional radiomic features from multiparametric MRI for predicting pretreatment survival in isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) patients is a promising approach. Methods: MRI data from 49 IDH wild-type glioblastoma patients pre-treatment were utilized. Diffusion and perfusion maps were generated, and tumor subregions segmented. Radiomic features were extracted for each tissue type and map. Feature selection on 1862 radiomic features identified 25 significant features. The Cox proportional-hazards model with LASSO regularization was used to perform survival analysis. Internal and external validation used a 38-patient training cohort and an 11-patient validation cohort. Statistical significance was set at p < 0.05. Results: Age and six radiomic features (shape and first and second order) from T1W, diffusion, and perfusion maps contributed to the final model. Findings suggest that a small necrotic subregion, inhomogeneous vascularization in the solid non-enhancing subregion, and edema-related tissue damage in the enhancing and edema subregions are linked to poor survival. The model's C-Index was 0.66 (95% C.I. 0.54-0.80). External validation demonstrated good accuracy (AUC > 0.65) at all time points. Conclusions: Radiomics analysis, utilizing segmented perfusion and diffusion maps, provide predictive indicators of survival in IDH wild-type glioblastoma patients, revealing associations with microstructural and vascular heterogeneity in the tumor.

Posterior reversible encephalopathy syndrome: a noteworthy syndrome in end-stage renal disease patients.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiologic entity characterized by headache, visual disturbances, seizures, and the presence of edema on MRI scan, predominantly in the posterior white matter. Regarding end-stage renal disease (ESRD) and PRES, only a few cases of children on peritoneal dialysis (PD) and adults on hemodialysis have been described in the literature. CASES: We report 4 cases of adult patients on PD who presented with PRES, all of which were due to hypertension and inadequate management of fluid balance. The patients expressed typical PRES symptoms such as headache, visual disorders, and tonic/clonic seizures. The patients recovered completely and the MRI lesions disappeared after strict control of volume status. CONCLUSION: Nephrologists should be aware of the syndrome, especially when they manage hypertensive ESRD patients not compliant with the fluid and diet restrictions. MRI scan is the only diagnostic tool for defining the syndrome. Early diagnosis is important, since complete remission is achieved after appropriate treatment.

A rare case report of simultaneous presentation of myopathy, Addison's disease, primary hypoparathyroidism, and Fanconi syndrome in a child diagnosed with Kearns-Sayre syndrome.

UNLABELLED: Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA deletion syndrome defined as the presence of ophthalmoplegia, pigmentary retinopathy, onset less than age 20 years, and one of the following: cardiac conduction defects, cerebellar syndrome, or cerebrospinal fluid protein above 100 mg/dl. KSS may affect many organ systems causing endocrinopathies, encephalomyopathy, sensorineural hearing loss, and renal tubulopathy. Clinical presentation at diagnosis is quite heterogeneous and, usually, few organs are affected with progression to generalized disease early in adulthood. We present the case of a boy with KSS presenting at the age of 5 years with myopathy, Addison's disease, primary hypoparathyroidism, and Fanconi syndrome. The proper replacement treatment along with the administration of mitochondrial metabolism-improving agents had a brief ameliorating effect, but gradual severe multisystemic deterioration was inevitable over the next 5 years. CONCLUSION: This report highlights the fact that in case of simultaneous presentation of polyendocrinopathies and renal disease early in childhood, KSS should be considered.

Brain Perfusion Changes in a Patient with Facial Trauma.

A 69-year-old male was admitted to our hospital because of left facial trauma with bone fractures, including the maxillary sinus, zygomatic arch, and ethmoid and sphenoid bones. Brain computed tomography was unremarkable but regional cerebral blood flow with hexamethyl-propylene-amine oxime single-photon emission computed tomography (SPECT) showed hypoperfusion of the left hemisphere, which was reversible since a repeat SPECT 4 months later was substantially improved. Brain perfusion SPECT may provide information on cerebrovascular status in some cases of facial injury.

The Role of Novel Imaging and Biofluid Biomarkers in Traumatic Axonal Injury: An Updated Review.

Traumatic brain injury (TBI) is a leading cause of disability worldwide. Traumatic axonal injury (TAI) is a subtype of TBI resulting from high-impact forces that cause shearing and/or stretching of the axonal fibers in white matter tracts. It is present in almost half of cases of severe TBI and frequently associated with poor functional outcomes. Axonal injury results from axonotomy due to mechanical forces and the activation of a biochemical cascade that induces the activation of proteases. It occurs at a cellular level; hence, conventional imaging modalities often fail to display TAI lesions. However, the advent of novel imaging modalities, such as functional magnetic resonance imaging and fiber tractography, has significantly improved the detection and characteristics of TAI. Furthermore, the significance of several fluid and structural biomarkers has also been researched, while the contribution of omics in the detection of novel biomarkers is currently under investigation. In the present review, we discuss the role of imaging modalities and potential biomarkers in diagnosing, classifying, and predicting the outcome in patients with TAI.

CNS involvement in primary Sjogren Syndrome: assessment of gray and white matter changes with MRI and voxel-based morphometry.

OBJECTIVE: The purpose of this study was to evaluate with MRI the involvement of gray matter and white matter structures in patients with primary Sjögren syndrome. SUBJECTS AND METHODS: Fifty-three patients with primary Sjögren syndrome, 18 age- and disease duration-matched patients with systemic sclerosis, and 35 age-matched control subjects were examined for differences in white matter hyperintensities (WMHIs) detected on FLAIR MR images. Differences in brain volume between patients with primary Sjögren syndrome and controls were studied by application of voxel-based morphometry to a 3D T1-weighted sequence. RESULTS: WMHIs were observed in 38 of the 53 patients with primary Sjögren syndrome, six of 18 patients with systemic sclerosis, and 17 of 35 controls. The numbers of WMHIs 2 mm or larger and the number smaller than 2 mm were higher in patients with primary Sjögren syndrome than in controls (≥ 2 mm, p = 0.004; < 2 mm, p < 0.001). No significant difference was observed in the number of WMHIs in primary Sjögren syndrome patients and that in systemic sclerosis patients. After control for age, a positive relation was found between disease duration and total number of WMHIs (p = 0.037) and number of WMHIs 2 mm or larger (p = 0.023) in patients with primary Sjögren syndrome. In comparison with the controls, patients with primary Sjögren syndrome had decreased gray matter volume in the cortex, deep gray matter, and cerebellum. Associated loss of white matter volume was observed in areas corresponding to gray matter atrophy and in the corpus callosum (p < 0.05). CONCLUSION: Patients with primary Sjögren syndrome have WMHIs and gray and white matter atrophy, probably related to cerebral vasculitis.

Differentiation Between True Tumor Progression of Glioblastoma and Pseudoprogression Using Diffusion-Weighted Imaging and Perfusion-Weighted Imaging: Systematic Review and Meta-analysis.

BACKGROUND: On brain magnetic resonance imaging, both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are used to evaluate cerebral tumors. The purpose of this meta-analysis was to evaluate and compare the diagnostic performance of DWI and PWI in differentiating between pseudoprogression and true tumor progression of glioblastoma. METHODS: We performed a systematic review of the PubMed database from January 2000 to December 2019 for relevant studies. After application of specific inclusion and exclusion criteria, the eligible articles were evaluated for methodologic quality and risk of bias using the updated Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool. From the published study results, the pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio and their corresponding confidence intervals (% CI), and the area under the curve, were calculated individually for DWI and PWI. RESULTS: The meta-analysis included 24 studies, with a total of 900 patients. DWI was found to be slightly superior in terms of sensitivity and specificity, 0.88 (% CI 0.83-0.92) and 0.85 (% CI 0.78-0.91), respectively, compared with the respective values of PWI, 0.85 (% CI 0.81-0.89) and 0.79 (% CI 0.74-0.84). On comparison of the overall diagnostic accuracy of the MRI modalities using their respective area under the curve values (0.9156 for DWI, 0.9072 for PWI), no significant difference was demonstrated between the 2. CONCLUSIONS: Both DWI and PWI provided optimal diagnostic performance in differentiating pseudoprogression from true tumor progression in cerebral glioblastoma, and neither technique proved to be superior.

Periventricular leukomalacia in preterm children: assessment of grey and white matter and cerebrospinal fluid changes by MRI.

BACKGROUND: Brain plasticity in patients with periventricular leukomalacia (PVL) may suggest grey matter (GM) changes. OBJECTIVE: To assess the volume of 116 GM areas and total volume of GM, white matter (WM) and cerebrospinal fluid (CSF) in preterm children with PVL, using the Statistical Parametric Mapping (SPM5) and the Individual Brain Atlases Statistical Parametric Mapping (IBASPM) toolboxes. MATERIALS AND METHODS: Ten preterm children (gestational age 31.7 +/- 4.2 weeks, corrected age 27.8 +/- 21.7 months) with PVL and 46 matched, preterm control subjects were studied using a three-dimensional T1-weighted sequence. Volumes were calculated using SPM5 and IBASPM. RESULTS: GM volume in frontal superior orbital, posterior cingulum and lingual gyrus, the putamen and thalamus was significantly higher in children with PVL (3.6 +/- 0.6 cm(3), 2.0 +/- 0.5 cm(3), 9.7 +/- 1.7 cm(3), 2.5 +/- 0.6 cm(3), 2.6 +/- 0.9 cm(3), respectively) than in controls (3.1 +/- 0.7 cm(3), 1.5 +/- 0.2 cm(3), 8.2 +/- 1.3 cm(3), 1.7 +/- 1.4 cm(3), 1.8 +/- 0.4 cm(3), respectively). White matter volume was lower (182.1 +/- 40.5 cm(3)) and CSF volume was higher (300.8 +/- 56.2 cm(3)) in children with PVL than in controls (222.9 +/- 67.2 cm(3), 219.0 +/- 61.8 cm(3), respectively), P < 0.05. No significant difference was found in the total GM volume and the volume of neocortex. CONCLUSION: Preterm children with PVL show regional GM volume increase, possibly explained by axonal sprouting, neuronal hypertrophy and neurogenesis, which in turn may reflect brain plasticity.

Solitary cystic cerebral metastasis from transitional cell carcinoma of the bladder.

Metastatic brain tumors are the most common intracranial neoplasm in adults. Bladder cancer gives metastasis to the brain in less than 1%. Herewith, we report on a case of a 71-year-old man who was admitted to the emergency department after an episode of loss of consciousness. On neurological examination a left hemiparesis was observed. The patient's previous history entailed a total cystectomy and radical prostatectomy 7 months ago because of a transitional cell carcinoma (TCC) of the urinary bladder. Brain imaging work-up revealed a cystic lesion with perifocal edema in the right frontal lobe. The patient was operated and the histological diagnosis was consistent with a metastatic carcinoma, with morphological, histochemical and immunohistochemical features comparable to those of the primary tumor. Postoperative the patient was in excellent neurological state and received complementary chemotherapy and total brain irradiation. Additional imaging and laboratory examinations excluded other metastatic lesion. The patient died 18 months later due to systemic disease. Although intracranial metastases from TCC of urinary bladder have a low incidence, in follow-up examinations any alterations in neurological status in these patients should be thoroughly evaluated.

Multifocal alterations of white matter accompany the transition from normal cognition to dementia in Parkinson's disease patients.

The purpose of the present study was to investigate the pattern of white matter (WM) changes associated with Parkinson's disease (PD)-related cognitive impairment by using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) measures. Diffusion Tensor Imaging (DTI) was performed in 21 PD-patients with dementia (PDD) and in an age-matched control group including 40 PD-patients without dementia (PD-CTRL). The Parkinson's disease-Cognitive Rating Scale (PD-CRS) was used for patients' neuropsychological assessment. Local microstructural WM differences associated with the presence of cognitive impairment were tested using tract-based spatial statistics analysis. Multiple regression models investigated the association of DTI indices with total PD-CRS score, PD-CRS raw items and other clinical measures across the whole study sample. Significant FA decreases were found in PDD compared to PD-CTRL patients mainly in the body of corpus callosum, corona radiata and cingulum. Lower PD-CRS score was significantly associated with decreased FA, MD and AD values in multiple WM tracts primarily located in prefrontal and limbic areas as well as across the corpus callosum. Lower performance in specific PD-CRS raw items was also associated with FA decreases in major WM tracts. The results suggest that multifocal microstructural changes of WM accompany the transition from normal to demented cognitive state in PD-patients. The corpus callosum, the corona radiata and the cingulum are among the regions mostly affected during this course. A progressive axonal degeneration is proposed as a key underlying mechanism.