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Recent studies associated rapid eye movement sleep behavior disorder (RBD) in Parkinson's disease (PD) with severe cognitive impairment and brain atrophy. However, whole-brain functional connectivity has never been explored in this group of PD patients. In this study, whole-brain network-based statistics and graph-theoretical approaches were used to characterize resting-state interregional functional connectivity in PD with probable RBD (PD-pRBD) and its relationship with cognition. Our sample consisted of 30 healthy controls, 32 PD without probable RBD (PD-non pRBD), and 27 PD-pRBD. The PD-pRBD group showed reduced functional connectivity compared with controls mainly involving cingulate areas with temporal, frontal, insular, and thalamic regions (p < 0.001). Also, the PD-pRBD group showed reduced functional connectivity between right ventral posterior cingulate and left medial precuneus compared with PD-non pRBD (p < 0.05). We found increased normalized characteristic path length in PD-pRBD compared with PD-non pRBD. In the PD-pRBD group, mean connectivity strength from reduced connections correlated with visuoperceptual task and normalized characteristic path length correlated with processing speed and verbal memory tasks. This work demonstrates the existence of disrupted functional connectivity in PD-pRBD, together with abnormal network integrity, that supports its consideration as a severe PD subtype., (© 2021. The Author(s).)

Background: Probabilistic tractography, in combination with graph theory, has been used to reconstruct the structural whole-brain connectome. Threshold-free network-based statistics (TFNBS) is a useful technique to study structural connectivity in neurodegenerative disorders; however, there are no previous studies using TFNBS in Parkinson's disease (PD) with and without mild cognitive impairment (MCI). Materials and Methods: Sixty-two PD patients, 27 of whom classified as PD-MCI, and 51 healthy controls (HC) underwent diffusion-weighted 3T magnetic resonance imaging. Probabilistic tractography, using FMRIB Software Library (FSL), was used to compute the number of streamlines (NOS) between regions. NOS matrices were used to find group differences with TFNBS, and to calculate global and local measures of network integrity using graph theory. A binominal logistic regression was then used to assess the discrimination between PD with and without MCI using non-overlapping significant tracts. Tract-based spatial statistics were also performed with FSL to study changes in fractional anisotropy (FA) and mean diffusivity. Results: PD-MCI showed 37 white matter connections with reduced connectivity strength compared with HC, mainly involving temporal/occipital regions. These were able to differentiate PD-MCI from PD without MCI with an area under the curve of 83-85%. PD without MCI showed disrupted connectivity in 18 connections involving frontal/temporal regions. No significant differences were found in graph measures. Only PD-MCI showed reduced FA compared with HC. Discussion: TFNBS based on whole-brain probabilistic tractography can detect structural connectivity alterations in PD with and without MCI. Reduced structural connectivity in fronto-striatal and posterior cortico-cortical connections is associated with PD-MCI.

Background: Three cortical atrophy patterns were previously identified in non-demented Parkinson's disease patients using a data-driven approach based on cortical thickness data: i) parieto-temporal pattern of atrophy with worse cognitive performance (pattern 1), ii) occipital and frontal cortical atrophy with younger disease onset (pattern 2), and iii) non-detectable cortical atrophy (pattern 3). We aimed to investigate the evolution of these three patterns over time., Methods: Magnetic resonance imaging and neuropsychological assessment were obtained at baseline and follow-up (3.8 ± 0.4 year apart) in a group of 45 Parkinson's disease patients and 22 healthy controls. FreeSurfer was used for cortical thickness analysis and global atrophy measures., Results: Temporo-parietal cortical thinning occurred in pattern 2, 3 and controls groups, and patients showed decline in processing speed (as measured by the Stroop Word-Color test, the Symbol Digits Modalities test and the Trail Making Test Part B) and in semantic fluency (animals). Pattern 3 patients showed more progressive cortical thinning in the left prefrontal cortex than controls and more right occipital thinning than pattern 2 patients over time. Pattern 1 patients had greater compromise in activities of the daily living and suffered higher attrition rate., Conclusion: The Parkinson's disease phenotypes identified using cluster analysis of cortical thickness data showed different progression over time. The presence of prefrontal thinning and younger disease onset at baseline was associated to less cortical degeneration, while non-atrophic patients progressed showing a temporo-parietal cortical thinning., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Diagnosis of mild cognitive impairment in Parkinson's disease (PD) is relevant because it is a marker for evolution to dementia. However, the selection of suitable tests to evaluate separate cognitive domains in mild cognitive impairment related to PD remains an open question. The current work aims to investigate the neuroanatomical correlates of several visuospatial/visuoperceptual tests using the same sample and a multimodal MRI approach., Methods: The study included 36 PD patients and 20 healthy subjects matched for age, sex, and education. The visuospatial/visuoperceptual tests selected were: Pentagon Copying Test (PCT), Judgment of Line Orientation Test (JLOT), Visual Form Discrimination Test (VFDT), Facial Recognition Test (FRT), Symbol Digit Modalities Test (SMDT), and clock copying task (CLOX2). FreeSurfer was used to assess cortical thickness, and tract-based spatial statistics was used for fractional anisotropy analysis., Results: Lower performance in the PCT, JLOT, and SDMT was associated with extensive cortical thickness reductions in lateral parietal and temporal regions. VFDT and CLOX2 did not show this common pattern and correlated with more limited medial occipito-temporal and occipito-parietal regions. Performance in all visuospatial/visuoperceptual tests correlated with fractional anisotropy in the corpus callosum., Conclusions: Our findings show that JLOT, SDMT, and PCT, in addition to differentiating patients from controls, are suitable visuospatial/visuoperceptual tests to reflect cortical thinning in lateral temporo-parietal regions in PD patients. We did not observe the dissociation between dorsal and ventral streams that was expected according to the neuropsychological classification of visuospatial and visuoperceptual tests. (JINS, 2018, 24, 33-44).

Background: Olfactory dysfunction is present in a large proportion of patients with Parkinson's disease (PD) upon diagnosis. However, its progression over time has been poorly investigated. The few available longitudinal studies lack control groups or MRI data., Objective: To investigate the olfactory changes and their structural correlates in non-demented PD over a four-year follow-up., Methods: We assessed olfactory function in a sample of 25 PD patients and 24 normal controls of similar age using the University of Pennsylvania Smell Identification test (UPSIT). Structural magnetic resonance imaging data, obtained with a 3-T Siemens Trio scanner, were analyzed using FreeSurfer software., Results: Analysis of variance showed significant group (F = 53.882; P < 0.001) and time (F = 6.203; P = 0.016) effects, but the group-by-time interaction was not statistically significant. UPSIT performance declined ≥1.5 standard deviations in 5 controls and 7 patients. Change in UPSIT scores of patients correlated positively with volume change in the left putamen, right thalamus, and right caudate nucleus., Conclusion: Olfactory loss over time in PD and controls is similar, but we have observed significant correlation between this loss and basal ganglia volumes only in patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Clinical variability in the Parkinson's disease phenotype suggests the existence of disease subtypes. We investigated whether distinct anatomical patterns of atrophy can be identified in Parkinson's disease using a hypothesis-free, data-driven approach based on cortical thickness data., Methods: T1-weighted 3-tesla MRI and a comprehensive neuropsychological assessment were performed in a sample of 88 nondemented Parkinson's disease patients and 31 healthy controls. We performed a hierarchical cluster analysis of imaging data using Ward's linkage method. A general linear model with cortical thickness data was used to compare clustering groups., Results: We observed 3 patterns of cortical thinning in patients when compared with healthy controls. Pattern 1 (n = 30, 34.09%) consisted of cortical atrophy in bilateral precentral gyrus, inferior and superior parietal lobules, cuneus, posterior cingulate, and parahippocampal gyrus. These patients showed worse cognitive performance when compared with controls and the other 2 patterns. Pattern 2 (n = 29, 32.95%) consisted of cortical atrophy involving occipital and frontal as well as superior parietal areas and included patients with younger age at onset. Finally, in pattern 3 (n = 29, 32.95%), there was no detectable cortical thinning. Patients in the 3 patterns did not differ in disease duration, motor severity, dopaminergic medication doses, or presence of mild cognitive impairment., Conclusions: Three cortical atrophy subtypes were identified in nondemented Parkinson's disease patients: (1) parieto-temporal pattern of atrophy with worse cognitive performance, (2) occipital and frontal cortical atrophy and younger disease onset, and (3) patients without detectable cortical atrophy. These findings may help identify prognosis markers in Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

Objective: To investigate the pattern of cortical thinning in Parkinson's disease (PD) across different disease stages and to elucidate to what extent cortical thinning is related to cognitive impairment., Design: Ninety-six subjects including 39 controls and 57 PD patients participated in this study. PD subjects were divided into three groups (early, n=24; moderate, n=18; with dementia, n=15). High field structural brain MRI images were acquired in a 3T scanner and analyses of cortical thickness and surface were carried out. Vertex-wise group comparisons were performed and cortical thickness was correlated with motor and cognitive measures., Results: We found a positive correlation between Mini-Mental State Examination scores and cortical thickness in the anterior temporal, dorsolateral prefrontal, posterior cingulate, temporal fusiform and occipitotemporal cortex. Unified Parkinson's Disease Rating Scale-III (motor subsection) scores showed a robust negative correlation with caudate volumes. We found that disease stage in PD was associated with thinning of the medial frontal (premotor and supplementary motor cortex), posterior cingulate, precuneus, lateral occipital, temporal and dorsolateral prefrontal cortex. Discriminant analysis and a receiver operating characteristics approach showed that mean cortical thickness and hippocampus volume have 80% accuracy in identifying PD patients with dementia. PD stage and PD dementia can be characterised by a specific pattern of cortical thinning., Conclusions: We conclude that measuring cortical thickness can be useful in assessing disease stage and cognitive impairment in patients with PD. In addition, cortical thickness may be useful in identifying dementia in PD.

The aim of this study was to investigate the progression of cortical thinning and gray-matter (GM) volume loss in early Parkinson's disease (PD). MRI and neuropsychological assessment were obtained at baseline and follow-up (mean ± standard deviation = 35.50 ± 1.88 months) in a group of 16 early-PD patients (H & Y stage ≤II and disease duration ≤5 years) and 15 healthy controls matched for age, gender, and years of education. FreeSurfer software was used for the analysis of cortical thickness as well as for cortical and subcortical volumetric analyses. Voxel-based morphometry analysis was performed using SPM8. Compared to controls, PD patients showed greater regional cortical thinning in bilateral frontotemporal regions as well as greater over-time total GM loss and amygdalar volume reduction. PD patients and controls presented similar over-time changes in cognitive functioning. In early-PD patients, global GM loss, amygdalar atrophy, and cortical thinning in frontotemporal regions are specifically associated with the PD-degenerative process., (Copyright © 2012 Movement Disorder Society.)

Noninvasive brain imaging methods provide useful information on cerebral involution and degenerative processes. Here we assessed cortical degeneration in 20 nondemented patients with Parkinson's disease (PD) and 20 healthy controls using three quantitative neuroanatomical approaches: voxel-based morphometry (VBM), cortical folding (BrainVisa), and cortical thickness (FreeSurfer). We examined the relationship between global and regional gray matter (GM) volumes, sulcal indices, and thickness measures derived from the previous methods as well as their association with cognitive performance, age, severity of motor symptoms, and disease stage. VBM analyses showed GM volume reductions in the left temporal gyrus in patients compared with controls. Cortical folding measures revealed significant decreases in the left frontal and right collateral sulci in patients. Finally, analysis of cortical thickness showed widespread cortical thinning in right lateral occipital, parietal and left temporal, frontal, and premotor regions. We found that, in patients, all global anatomical measures correlated with age, while GM volume and cortical thickness significantly correlated with disease stage. In controls, a significant association was found between global GM volume and cortical folding with age. Overall these results suggest that the three different methods provide complementary and related information on neurodegenerative changes occurring in PD, however, surface-based measures of cortical folding and especially cortical thickness seem to be more sensitive than VBM to identify regional GM changes associated to PD., (Copyright © 2011 Wiley Periodicals, Inc.)

We aimed to investigate changes in the verbal recognition memory network in patients with early Parkinson's disease (PD) without overt recognition memory alteration. Verbal recognition memory was assessed in 24 PD patients in early stages of the disease and a control group of 24 healthy subjects during fMRI data acquisition. Participants were presented with a list of 35 words before imaging, and later during fMRI scanning they were required to recognize these previously presented words. Both model-based (FEAT) and model-free (MELODIC) analyses of the fMRI data were carried out with FSL software. Memory was also assessed by means of Rey's Auditory Verbal Learning Test (RAVLT). PD patients showed no difference in the fMRI recognition memory task and recognition memory assessed by the RAVLT compared to healthy controls. Model-based analysis did not show significant differences between groups. On the other hand, model-free analysis identified components that fitted the task-model and were common to all the participants, as well as components that differed between PD and healthy controls. PD patients showed decreased task-related activations in areas involved in the recognition memory network and decreased task-related deactivations in the default mode network in comparison with controls. In conclusion, model-free fMRI analysis detected alterations in functional cerebral networks involved in a verbal memory task in PD patients without evident recognition memory deficit., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Olfactory dysfunction is known to occur before the appearance of the classical motor signs in Parkinson's disease (PD) and diffusion tensor imaging (DTI) studies in PD have reported fractional anisotropy (FA) reductions in the early disease stages. We aimed to investigate the relationship between olfactory dysfunction and white matter (WM) FA of central olfactory areas in early PD. Twenty-four patients at Hoehn and Yahr stages I and II and 24 healthy controls matched by age, gender and years of education participated in this study. DTI was acquired at a 3 Tesla scanner and odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). We performed FA voxelwise group comparisons in the central olfactory structures using tract-based spatial statistics (TBSS) and correlation analyses between FA values in these central olfactory areas and UPSIT scores. Patients with severe microsmia (UPSIT between 19 and 25) and anosmia (UPSIT lower or equal to 18) had lower FA values than PD patients with mild/moderate or no olfactory dysfunction (UPSIT between 26 and 40) and healthy controls in the WM adjacent to gyrus rectus. In addition, patients with anosmia had reduced FA in the WM surrounding primary olfactory areas in comparison with healthy controls. FA values in the WM adjacent to primary olfactory cortex and right gyrus rectus correlated with UPSIT scores in the PD group. This study demonstrates, for the first time, that microstructural WM reductions are present in the central olfactory system of early stage PD patients and that these reductions are associated with reduced ability to smell., (© 2010 Movement Disorder Society.)

Objective: To determine the course of cognitive deficits and the regional progression of brain atrophy in patients with Parkinson's disease (PD) with and without visual hallucinations (VH)., Methods: The authors performed MRI and neuropsychological assessment at entry to the study and at follow-up (mean+/-SD=29.91+/-5.74 months) in a sample of initially non-demented 12 PD patients with VH, 14 PD patients without VH and 12 healthy controls (HC). Grey-matter changes over time were assessed by means of voxel-based morphometry (VBM) and cognitive changes by an extensive neuropsychological battery., Results: At follow-up, 75% of patients with VH developed dementia. The greatest decline was observed in verbal memory, semantic fluency, language comprehension and visuoperceptive functions. None of the patients without VH met criteria for dementia and did not show any worsening in cognitive functions over time. Patients with VH showed widespread limbic, paralimbic and neocortical grey-matter loss, whereas in the PD without VH group, grey-matter loss was restricted to a small region in the frontal cortex and cerebellum. The authors also found significant correlations between the changes in several cognitive functions and grey-matter loss over time in PD patients with VH., Conclusion: The presence of VH in PD determines a different cognitive outcome and a different pattern of progressive brain atrophy. PD patients with VH, unlike PD without VH, frequently develop dementia and show a widespread atrophy involving limbic, paralimbic and neocortical areas.

Decision-making and recognition of emotions are often impaired in patients with Parkinson's disease (PD). The orbitofrontal cortex (OFC) and the amygdala are critical structures subserving these functions. This study was designed to test whether there are any structural changes in these areas that might explain the impairment of decision-making and recognition of facial emotions in early PD. We used the Iowa Gambling Task (IGT) and the Ekman 60 faces test which are sensitive to the integrity of OFC and amygdala dysfunctions in 24 early PD patients and 24 controls. High-resolution structural magnetic resonance images (MRI) were also obtained. Group analysis using voxel-based morphometry (VBM) showed significant and corrected (P < 0.05 FEW-small volume correction) gray matter (GM) loss in the right amygdala and bilaterally in the OFC in PD patients. Volumetric analyses were also performed but did not yield significant differences between groups. Left lateral GM volume in OFC showed a slight correlation with the IGT, and bilateral OFC GM was strongly correlated with Ekman test performance in PD patients. We conclude that: (i) impairment in decision-making and recognition of facial emotions occurs at the early stages of PD, (ii) these neuropsychological deficits are accompanied by degeneration of OFC and amygdala, and (iii) bilateral OFC reductions are associated with impaired recognition of emotions, and GM volume loss in left lateral OFC is related to decision-making impairment in PD.