Alterations in Brain Network Organization in Adults With Obesity as Compared With Healthy-Weight Individuals and Seniors.

OBJECTIVE: Life expectancy and obesity rates have drastically increased in recent years. An unhealthy weight is related to long-lasting medical disorders that might compromise the normal course of aging. The aim of the current study of brain connectivity patterns was to examine whether adults with obesity would show signs of premature aging, such as lower segregation, in large-scale networks. METHODS: Participants with obesity (n = 30, mean age = 32.8 ± 5.68 years) were compared with healthy-weight controls (n = 33, mean age = 30.9 ± 6.24 years) and senior participants who were stroke-free and without dementia (n = 30, mean age = 67.1 ± 6.65 years) using resting-state magnetic resonance imaging and graph theory metrics (i.e., small-world index, clustering coefficient, characteristic path length, and degree). RESULTS: Contrary to our hypothesis, participants with obesity exhibited a higher clustering coefficient compared with senior participants (t = 5.06, p < .001, d = 1.23, 95% CIbca = 0.64 to 1.88). Participants with obesity also showed lower global degree relative to seniors (t = -2.98, p = .014, d = -0.77, 95% CIbca = -1.26 to -0.26) and healthy-weight controls (t = -2.92, p = .019, d = -0.72, 95% CIbca = -1.19 to -0.25). Regional degree alterations in this group were present in several functional networks. CONCLUSIONS: Participants with obesity displayed greater network clustering than did seniors and also had lower degree compared with seniors and individuals with normal weight, which is not consistent with the notion that obesity is associated with premature aging of the brain. Although the cross-sectional nature of the study precludes causal inference, the overly clustered network patterns in obese participants could be relevant to age-related changes in brain function because regular networks might be less resilient and metabolically inefficient.

Impaired Structural Connectivity in Parkinson's Disease Patients with Mild Cognitive Impairment: A Study Based on Probabilistic Tractography.

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.

Progression of Parkinson's disease patients' subtypes based on cortical thinning: 4-year follow-up.

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 ±â€¯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.

Cortical atrophy patterns in early Parkinson's disease patients using hierarchical cluster analysis.

INTRODUCTION: Cortical brain atrophy detectable with MRI in non-demented advanced Parkinson's disease (PD) is well characterized, but its presence in early disease stages is still under debate. We aimed to investigate cortical atrophy patterns in a large sample of early untreated PD patients using a hypothesis-free data-driven approach. METHODS: Seventy-seven de novo PD patients and 50 controls from the Parkinson's Progression Marker Initiative database with T1-weighted images in a 3-tesla Siemens scanner were included in this study. Mean cortical thickness was extracted from 360 cortical areas defined by the Human Connectome Project Multi-Modal Parcellation version 1.0, and a hierarchical cluster analysis was performed using Ward's linkage method. A general linear model with cortical thickness data was then used to compare clustering groups using FreeSurfer software. RESULTS: We identified two patterns of cortical atrophy. Compared with controls, patients grouped in pattern 1 (n = 33) were characterized by cortical thinning in bilateral orbitofrontal, anterior cingulate, and lateral and medial anterior temporal gyri. Patients in pattern 2 (n = 44) showed cortical thinning in bilateral occipital gyrus, cuneus, superior parietal gyrus, and left postcentral gyrus, and they showed neuropsychological impairment in memory and other cognitive domains. CONCLUSIONS: Even in the early stages of PD, there is evidence of cortical brain atrophy. Neuroimaging clustering analysis is able to detect two subgroups of cortical thinning, one with mainly anterior atrophy, and the other with posterior predominance and worse cognitive performance.

Structural Brain Correlations of Visuospatial and Visuoperceptual Tests in Parkinson's Disease.

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).

Patterns of cortical thinning in nondemented Parkinson's disease patients.

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.

Resting-state frontostriatal functional connectivity in Parkinson's disease-related apathy.

One of the most common neuropsychiatric symptoms in Parkinson's disease (PD) is apathy, affecting between 23% and 70% of patients and thought to be related to frontostriatal dopamine deficits. In the current study, we assessed functional resting-state frontostriatal connectivity and structural changes associated with the presence of apathy in a large sample of PD subjects and healthy controls, while controlling for the presence of comorbid depression and cognitive decline. Thirty-one healthy controls (HC) and 62 age-, sex-, and education-matched PD patients underwent resting-state functional magnetic resonance imaging (MRI). Apathy symptoms were evaluated with the Apathy Scale (AS). The 11 Beck Depression Inventory-II items that measure dysphoric mood symptoms as well as relevant neuropsychological scores were used as nuisance factors in connectivity analyses. Voxel-wise analyses of functional connectivity between frontal lobes (limbic, executive, rostral motor, and caudal motor regions), striata (limbic, executive, sensorimotor regions), and thalami were performed. Subcortical volumetry/shape analysis and fronto-subcortical voxel-based morphometry were performed to assess associated structural changes. Twenty-five PD patients were classified as apathetic (AS > 13). Apathetic PD patients showed functional connectivity reductions compared with HC and with non-apathetic patients, mainly in left-sided circuits, and predominantly involving limbic striatal and frontal territories. Similarly, severity of apathy negatively correlated with connectivity in these circuits. No significant effects were found in structural analyses. Our results indicate that the presence of apathy in PD is associated with functional connectivity reductions in frontostriatal circuits, predominating in the left hemisphere and mainly involving its limbic components.

Cognitive impairment and resting-state network connectivity in Parkinson's disease.

The purpose of this work was to evaluate changes in the connectivity patterns of a set of cognitively relevant, dynamically interrelated brain networks in association with cognitive deficits in Parkinson's disease (PD) using resting-state functional MRI. Sixty-five nondemented PD patients and 36 matched healthy controls were included. Thirty-four percent of PD patients were classified as having mild cognitive impairment (MCI) based on performance in attention/executive, visuospatial/visuoperceptual (VS/VP) and memory functions. A data-driven approach using independent component analysis (ICA) was used to identify the default-mode network (DMN), the dorsal attention network (DAN) and the bilateral frontoparietal networks (FPN), which were compared between groups using a dual-regression approach controlling for gray matter atrophy. Additional seed-based analyses using a priori defined regions of interest were used to characterize local changes in intranetwork and internetwork connectivity. Structural group comparisons through voxel-based morphometry and cortical thickness were additionally performed to assess associated gray matter atrophy. ICA results revealed reduced connectivity between the DAN and right frontoinsular regions in MCI patients, associated with worse performance in attention/executive functions. The DMN displayed increased connectivity with medial and lateral occipito-parietal regions in MCI patients, associated with worse VS/VP performance, and with occipital reductions in cortical thickness. In line with data-driven results, seed-based analyses mainly revealed reduced within-DAN, within-DMN and DAN-FPN connectivity, as well as loss of normal DAN-DMN anticorrelation in MCI patients. Our findings demonstrate differential connectivity changes affecting the networks evaluated, which we hypothesize to be related to the pathophysiological bases of different types of cognitive impairment in PD.

Cortical thinning associated with mild cognitive impairment in Parkinson's disease.

The aim of this study was to investigate patterns of cortical atrophy associated with mild cognitive impairment in a large sample of nondemented Parkinson's disease (PD) patients, and its relation with specific neuropsychological deficits. Magnetic resonance imaging (MRI) and neuropsychological assessment were performed in a sample of 90 nondemented PD patients and 32 healthy controls. All underwent a neuropsychological battery including tests that assess different cognitive domains: attention and working memory, executive functions, memory, language, and visuoperceptual-visuospatial functions. Patients were classified according to their cognitive status as PD patients without mild cognitive impairment (MCI; n = 43) and PD patients with MCI (n = 47). Freesurfer software was used to obtain maps of cortical thickness for group comparisons and correlation with neuropsychological performance. Patients with MCI showed regional cortical thinning in parietotemporal regions, increased global atrophy (global cortical thinning, total gray matter volume reduction, and ventricular enlargement), as well as significant cognitive impairment in memory, executive, and visuospatial and visuoperceptual domains. Correlation analyses showed that all neuropsychological tests were associated with cortical thinning in parietotemporal regions and to a lesser extent in frontal regions. These results provide neuroanatomic support to the concept of MCI classified according to Movement Disorders Society criteria. The posterior pattern of atrophy in temporoparietal regions could be a structural neuroimaging marker of cognitive impairment in nondemented PD patients. All of the neuropsychological tests reflected regional brain atrophy, but no specific patterns were seen corresponding to impairment in distinct cognitive domains.

Functional brain networks and cognitive deficits in Parkinson's disease.

Graph-theoretical analyses of functional networks obtained with resting-state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are associated with changes in global and local network measures. Thirty-six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting-state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long-range connections as well as increased local interconnectedness manifested as higher measures of clustering, small-worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker.

Neuroanatomical correlates of olfactory loss in normal aged subjects.

In non-demented older persons, smell dysfunction, measured premortem, has been associated with postmortem brain degeneration similar to that of Alzheimer's disease. We hypothesized that distinct measures of gray and white matter integrity evaluated through magnetic resonance imaging (MRI) techniques could detect degenerative changes associated with age-related olfactory dysfunction. High-resolution T1-weighted images and diffusion-tensor images (DTI) of 30 clinically healthy subjects aged 51-77 were acquired with a 3-Tesla MRI scanner. Odor identification performance was assessed by means of the University of Pennsylvania Smell Identification Test (UPSIT). UPSIT scores correlated with right amygdalar volume and bilateral perirhinal and entorhinal cortices gray matter volume. Olfactory performance also correlated with postcentral gyrus cortical thickness and with fractional anisotropy and mean diffusivity levels in the splenium of the corpus callosum and the superior longitudinal fasciculi. Our results suggest that age-related olfactory loss is accompanied by diffuse degenerative changes that might correspond to the preclinical stages of neurodegenerative processes.

Progressive changes in a recognition memory network in Parkinson's disease.

BACKGROUND: In a previous functional MRI (fMRI) study, we found that patients with Parkinson's disease (PD) presented with dysfunctions in the recruitment of recognition memory networks. We aimed to investigate the changes in these networks over time. METHODS: We studied 17 PD patients and 13 age and sex matched healthy subjects. In both groups fMRI (recognition memory paradigm) and neuropsychological assessments were obtained at baseline and at follow-up. To analyse changes over time in functional networks, model free (independent component analysis) analyses of the fMRI data were carried out. Then, a cross correlation approach was used to assess the changes in the strength of functional connectivity. RESULTS: At follow-up, patients showed reduced recruitment of one network, including decreased activation in the orbitofrontal cortices, middle frontal gyri, frontal poles, anterior paracingulate cortex, superior parietal lobes and left middle temporal gyrus, as well as decreased deactivation in the anterior paracingulate gyrus and precuneus. Cross correlation analyses over time showed a decrease in the strength of functional connectivity between the middle frontal gyrus and the superior parietal lobe in PD patients. CONCLUSIONS: Model free fMRI and cross correlation connectivity analyses were able to detect progressive changes in functional networks involved in recognition memory in PD patients at early disease stages and without overt clinical deterioration. Functional connectivity analyses could be useful to monitor changes in brain networks underlying neuropsychological deficits in PD.

Sexually-transmitted viral diseases in women: clinical and epidemiological aspects and advances in laboratory diagnosis.

Sexually transmitted diseases (STDs) have long been known, but they have only recently been recognized as causes of significant long-term morbidity, mainly as a result of increased knowledge concerning viral STDs. The relationship of these diseases with conditions such as anogenital cancer and acquired immunodeficiency syndrome (AIDS) has made viral STDs an important issue in the healthcare of women and infants, and in reproductive health. The evolution of the AIDS pandemic is now characterized by growing differences between rich and poor nations. New diagnostic tools include rapid tests of blood, urine and saliva samples. New techniques, such as computerized cytology, have been developed for the diagnosis of human papillomavirus (HPV). Women infected with HIV are at a greater risk of being co-infected with HPV, and they are also more prone to the progression and persistence of HPV lesions. The herpes simplex virus presents high rates of co-infection with HIV, and it plays a particularly important role in increasing transmission rates of this virus.

Sexually-transmitted viral diseases in women: clinical and epidemiological aspects and advances in laboratory diagnosis

Sexually transmitted diseases (STDs) have long been known, but they have only recently been recognized as causes of significant long-term morbidity, mainly as a result of increased knowledge concerning viral STDs. The relationship of these diseases with conditions such as anogenital cancer and acquired immunodeficiency syndrome (AIDS) has made viral STDs an important issue in the healthcare of women and infants, and in reproductive health. The evolution of the AIDS pandemic is now characterized by growing differences between rich and poor nations. New diagnostic tools include rapid tests of blood, urine and saliva samples. New techniques, such as computerized cytology, have been developed for the diagnosis of human papillomavirus (HPV). Women infected with HIV are at a greater risk of being co-infected with HPV, and they are also more prone to the progression and persistence of HPV lesions. The herpes simplex virus presents high rates of co-infection with HIV, and it plays a particularly important role in increasing transmission rates of this virus.