Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Widespread cortical and subcortical brain atrophy in Parkinson’s disease with excessive daytime sleepiness

Our aim was to determine regional brain atrophy in Parkinson’s disease (PD) patients with excessive daytime sleepiness (EDS) using voxel-based morphometry (VBM). From 71 consecutive probable PD patients, nine non-demented and non-hallucinating patients with an Epworth Sleepiness Scale (ESS) ≥ 10 and 13 PD patients with an ESS ≤ 3 were selected as having EDS and as not having EDS, respectively. We also enrolled 22 healthy age- and sex-matched controls. Regional brain atrophy was assessed using VBM with 3-T magnetic resonance imaging. There was no difference in the dosage of dopaminergic drugs between PD patients with EDS and PD patients without EDS. PD patients with EDS showed marked atrophy in the gray matter of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to controls (false discovery rate corrected p < 0.05). In contrast, PD patients without EDS did not show any significant difference in gray matter atrophy compared to controls (false discovery rate corrected p < 0.05). PD patients with EDS showed significant atrophy of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to PD patients without EDS (uncorrected p < 0.001). PD patients with EDS, even without dementia and hallucination, showed significant gray matter atrophy compared to PD patients without EDS and controls.     

A combined voxel-based morphometry and 1H-MRS study in patients with Friedreich’s ataxia

Friedreich’s ataxia (FA) is the most frequent autosomal recessive ataxia and essentially considered a disease of the dorsal root ganglia and spinal cord. It is caused by homozygous GAA expansions in the Frataxin gene in most cases. Although only a few studies have addressed cerebral involvement in FA, cognitive symptoms have lately been emphasized. To evaluate brain damage in vivo, we employed whole-brain VBM and analysis of pre-defined regions of interest (ROIs) over the cerebellum to compare 24 patients with 24 age-and-sex-matched normal controls. ¹H-MRS of deep cerebral white matter (WM) was subsequently performed. Mean age of patients was 28 years (range 14–45), mean duration of disease was 14 years (range 5–28) and 11 were men. Mean length of shorter (GAA1) and longer (GAA2) alleles were 735 and 863, respectively. VBM analysis identified WM atrophy in the posterior cyngulate gyrus, paracentral lobule and middle frontal gyrus. ROIs over the infero-medial cerebellar hemispheres and dorsal brainstem presented gray matter atrophy, which correlated with duration of disease (r = −0.4). NAA/Cr ratios were smaller among patients (P = 0.006), but not Cho/Cr (P = 0.08). Our results provide evidence of axonal damage in the cerebellum, brainstem and subcortical WM in FA. This suggests that neuronal dysfunction is more widespread than previously thought in FA.     

Olfactory performance acts as a cognitive reserve in non-demented patients with Parkinson's disease

ObjectiveTo explore whether olfactory performance acts as a cognitive reserve in non-demented patients with Parkinson's disease (PD).MethodsPatients with non-demented PD (n = 119) underwent T1-weighted MRI and olfactory identification tests. According to their olfactory performance, PD patients were subdivided into three groups of high score (PD-H, n = 38), middle score (PD-M, n = 48), and low score (PD-L, n = 33). We investigated the pattern of gray matter (GM) density according to olfactory performance using voxel-based morphometry (VBM) and analyzed the correlation between GM density and olfactory performance.ResultsNo significant differences in demographic characteristics were observed among the groups. A neuropsychological test showed that cognitive deficits in verbal memory function were more severe in the PD-L group than in the PD-H group. However, a VBM analysis revealed that patients in the PD-H group possessed significantly decreased GM density in the bilateral temporal areas, orbitofrontal areas, mesiofrontal areas extending into the cingulate gyrus, and prefrontal areas, compared with patients in the PD-L group. No areas exhibiting a significant difference in GM density were observed between the PD-H and PD-M groups. Olfactory performance in patients with PD was negatively correlated with both the brain GM volume and intracerebral volume; in particular, GM density in the caudate nucleus and putamen exhibited a negative correlation with olfactory performance.ConclusionsOur data show that a high olfactory performance may compensate GM volume loss in order to minimize the exhibition of cognitive impairment and thus may act as a cognitive reserve in non-demented patients with PD.     

Longitudinal evaluation of cerebral morphological changes in Parkinson's disease with and without dementia

Objective To investigate the pattern of brain atrophy across time in a sample of Parkinson's disease (PD) patients with and without dementia using voxelbased morphometry (VBM) analysis. Methods The initial sample comprised thirteen non–demented PD patients and sixteen demented patients. Longitudinal cognitive assessment and structural MRI were performed. The mean follow–up period was 25 months (SD = 5.2). From this initial group, eight PD patients with dementia (5 men and 3 women) and eleven PD patients without dementia (7 men and 4 women) were reevaluated. MRI 3D structural images were acquired and analyzed by means of the optimized VBM procedure with Statistical Parametric Mapping (SPM2). Results VBM analysis showed a progressive grey matter volume decrease in patients with PD without dementia in limbic, paralimbic and neocortical associative temporooccipital regions. In patients with dementia the loss mainly involved neocortical regions. Conclusion VBM revealed a significant loss of grey matter volume in PD patients with and without dementia with disease progression. The decrease in limbic and paralimbic regions is widespread in non–demented patients. Neocortical volume reduction is the most relevant finding in patients with dementia. This suggests that the neocortex is a substrate for dementia in Parkinson disease.     

Hierarchical cluster analysis of multimodal imaging data identifies brain atrophy and cognitive patterns in Parkinson’s disease

BackgroundParkinson's disease (PD) is a heterogeneous condition. Cluster analysis based on cortical thickness has been used to define distinct patterns of brain atrophy in PD. However, the potential of other neuroimaging modalities, such as white matter (WM) fractional anisotropy (FA), which has also been demonstrated to be altered in PD, has not been investigated.ObjectiveWe aim to characterize PD subtypes using a multimodal clustering approach based on cortical and subcortical gray matter (GM) volumes and FA measures.MethodsWe included T1-weighted and diffusion-weighted MRI data from 62 PD patients and 33 healthy controls. We extracted mean GM volumes from 48 cortical and 17 subcortical regions using FSL-VBM, and the mean FA from 20 WM tracts using Tract-Based Spatial Statistics (TBSS). Hierarchical cluster analysis was performed with the PD sample using Ward's linkage method. Whole-brain voxel-wise intergroup comparisons of VBM and TBSS data were also performed using FSL. Neuropsychological and demographic statistical analyses were conducted using IBM SPSS Statistics 25.0.ResultsWe identified three PD subtypes, with prominent differences in GM patterns and little WM involvement. One group (n = 15) with widespread cortical and subcortical GM volume and WM FA reductions and pronounced cognitive deficits; a second group (n = 21) with only cortical atrophy limited to frontal and temporal regions and more specific neuropsychological impairment, and a third group (n = 26) without detectable atrophy or cognition impairment.ConclusionMultimodal MRI data allows classifying PD patients into groups according to GM and WM patterns, which in turn are associated with the cognitive profile.     

Insight and regional brain volumes in schizophrenia

We have investigated the relationship between insight impairment and regional brain volumes (gray and white matter) in schizophrenia using voxel-based morphometry (VBM). Fifty patients with schizophrenia were evaluated using the Scale for Unawareness of Mental Disorders. Magnetic resonance images were acquired, segmented and spatially normalized using optimized VBM routines. No significant inverse correlations were detected between insight impairment and gray or white matter volumes in the prefrontal region (where significant findings had been predicted a priori), or in any other brain areas. Our results do not support previous hypotheses suggesting a relationship between frontal lobe atrophy and impaired insight in patients with schizophrenia.     

Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease

BackgroundHallucinations are a frequent and severe complication in Parkinson's disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD.In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM).MethodsWe prospectively collected a sample of 46 non-demented PD patients, with (N = 17) and without (n = 29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function. Presence and type of minor psychotic phenomena was assessed by the new MDS-UPDRS. Three dimensional T1-weighted MRI images were acquired with a 1.5 T magnet, and analyzed using optimized VBM.ResultsCompared to controls, PD with minor hallucinations (PD-mH) showed reduced gray matter volume bilaterally in different areas of the dorsal visual stream, and in functionally related midbrain and cerebellar structures. Additionally, bilateral gray matter volume increases were observed in the PD-mH group in limbic and paralimbic regions.ConclusionsOur data support a major role of the dorsal visual stream in the genesis of minor hallucinations in PD, reinforcing the importance of posterior cortical regions for the development of cognitive and psychiatric complications in PD.     

Diversity in verbal fluency performance and its associations with MRI-informed brain age matrices in normal ageing and neurocognitive disorders

Introduction

Category verbal fluency test (CVFT) has been widely used to assess and monitor the cognitive capacities in epidemiological studies and clinical trials. Pronounced discrepancy in CVFT performance has been found in individuals with different cognitive statuses. This study aimed to combine the psychometric and morphometric approaches to decode the complex verbal fluency performance in senior adults with normal ageing and neurocognitive disorders.

Methods

This study adopted a two-stage cross-sectional design involving quantitative analyses of neuropsychological and neuroimaging data. In study I, capacity- and speed-based measures of CVFT were developed to evaluate the verbal fluency performance in normal ageing seniors (n = 261), those with mild cognitive impairment (n = 204), and those with dementia (n = 23) whose age range is from 65 to 85 years. In study II, structural magnetic resonance imaging-informed gray matter volume (GMV) and brain age matrices were calculated in a subsample (n = 52) from Study I through surface-based morphometry analysis. With age and gender as covariates, Pearson's correlation analysis was used to examine the associations of CVFT measures, GMV, and brain age matrices.

Results

Speed-based measures showed extensive and stronger associations with other cognitive functions than capacity-based measures. The component-specific CVFT measures showed shared and unique neural underpinnings with lateralized morphometric features. Moreover, the increased CVFT capacity was significantly correlated with younger brain age in mild neurocognitive disorder (NCD) patients.

Conclusion

We found that the diversity of verbal fluency performance in normal ageing and NCD patients could be explained by a combination of memory, language, and executive abilities. The component-specific measures and related lateralized morphometric correlates also highlight the underlying theoretical meaning of verbal fluency performance and its clinical utility in detecting and tracing the cognitive trajectory in individuals with accelerated ageing.     

How do cognitive and axial motor signs correlate in Parkinson’s disease? A 6-year prospective study

Impairment of Parkinson’s disease (PD) axial motor signs (AMS) has been described as a risk factor for dementia. Executive dysfunction is an important feature in recently proposed clinical diagnostic criteria for PD dementia. To clarify the relationship between AMS progression and executive cognitive performance, we conducted a 6-year prospective study in PD patients without AMS impairment at baseline. A hospital-based cohort of PD patients (n = 24) without dementia, in the initial motor stage (Hoehn–Yahr ≤ 2), and matched controls (n = 20) were followed prospectively over a 6-year period. Neuropsychological tests were performed in both groups, and motor function (including AMS: speech, gait, postural instability) was evaluated in the PD group. The PD group had a significantly higher decline in neuropsychological test scores than did the controls. Most of the neuropsychological and motor decline occurred in the last 4 years. In UPDRS III, progression of AMS and especially speech were the most important motor variables related to dementia. There was a correlation between speech impairment progression and declines in MMSE (r = −0.598, p = 0.002), Clock Drawing (r = −0.671, p < 0.001), Semantic Verbal Fluency (r = −0.435, p = 0.034), Alternating Sequences (r = 0.497, p = 0.014), and Raven’s Coloured Progressive Matrices (r = −0.735, p < 0.001). PD patients with higher speech impairment progression showed more rapid declines in some neuropsychological tests. Further studies are needed to clarify the different roles of speech, gait and postural instability on the initial phases of cognitive dysfunction.     

Pre-existing brain damage and association between severity and prior cognitive impairment in ischemic stroke patients

BackgroundWe evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS).MethodsIS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity.ResultsAmong the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages.ConclusionImpaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage.     

Voxel-based morphometry and intellectual assessment in patients with congenital bilateral perisylvian syndrome

Congenital bilateral perisylvian syndrome (CBPS) presents with heterogeneous clinical manifestations such as pseudobulbar palsy, language disorder, variable cognitive deficits, epilepsy, and perisylvian abnormalities (most frequently polymicrogyria) on imaging studies. We investigated the relationship between seizures and extent of gray matter (GM) and white matter (WM) abnormalities using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI) as well the association between seizures, structural abnormalities and cognitive ability. In this cross-sectional study, we evaluated 51 healthy volunteers and 18 patients with CBPS with epilepsy (seizure group, n = 7) and without (non-seizure group, n = 11). We used VBM (SPM8/DARTEL) to investigate areas with excess and atrophy of both gray and white matter, comparing groups of patients with controls. Intellectual ability of patients was assessed by the WISC-III or WAIS-III. Both groups with CBPS and the control group were homogeneous with respect to gender (p = 0.07) and age (p = 0.065). Besides perisylvian polymicrogyria, the seizure group exhibited areas with GM and WM reduction including temporal, frontal, parietal and occipital lobes. In contrast, we identified fewer areas with GM and WM reduction in the non-seizure group. The seizure group presented worse intellectual performance (performance IQ and global IQ) than the non-seizure group. The seizure group presented with a more widespread pattern of cortical and sub-cortical abnormalities, as well as worse cognition. Our results suggest that patients with CBPS and epilepsy appear to have widespread neuronal damage that goes beyond the areas with MRI-visible perisylvian polymicrogyria.     

Ventricular dilatation and brain atrophy in patients with Parkinson's disease with incipient dementia

Age‐related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patients developing cognitive decline. Older nondemented patients with Parkinson's disease (33) and age‐ and sex‐matched controls (39) were recruited and prospectively assessed for the development of significant cognitive decline over 36 months. Magnetic resonance imaging was obtained every 18 months, and ventricular volume and total brain gray and white matter volumes were measured using reliable segmentation of T1‐weighted volumetric scans. Subjects with incidental intracranial abnormalities, an atypical course, and stroke as well as dropouts were excluded from a cohort of 52 patients and 50 controls. Among 33 patients and 39 controls, 10 patients and 3 controls developed significant cognitive impairment or dementia. Ventricular change and Parkinson's disease status were significantly associated with dementia. Ventricular change was significantly correlated with change in Mini‐Mental Status Examination in the Parkinson's disease with dementia group (r = 0.87, P = .001). Gray matter atrophy was greater in Parkinson's disease with dementia, with similar change over time in both Parkinson's disease and Parkinson's disease with dementia. White matter volumes were not significantly different between Parkinson's disease and Parkinson's disease with dementia; however, the decrease over time might be greater in Parkinson's disease with dementia. Ventricular dilatation occurs early in the course of significant cognitive decline in patients with Parkinson's disease, possibly reflecting both cortical gray and white matter loss. © 2011 Movement Disorder Society     

Neuropsychiatric symptoms in Parkinson's disease: Fronto-striatal atrophy contributions

BackgroundNeuropsychiatric symptoms (NPS) in Parkinson's disease (PD) have been mostly attributed to neurotransmitter imbalances. However, recent findings suggest that gray matter atrophy also contributes to NPS in PD. We contrast PD patients with different levels of NPS, who are well-matched for dopaminergic medication levels and disease stage, to identify the fronto-striatal gray matter atrophy areas associated with NPS in PD.MethodsFifty mild, non-demented PD patients were included. We median-split the group via a neuropsychiatric screening tool (Cambridge Behavioural Inventory-Revised), which resulted in higher vs. lower NPS groups (n = 25 in each group). Using T1 brain scans acquired on a 3 Tesla MRI scanner, voxel-based morphometry analysis was applied to characterize the pattern of fronto-striatal gray matter atrophy associated with elevated NPS.ResultsWe found that the higher NPS group was characterized by greater atrophy in the prefrontal cortex, but not striatal areas. This was further corroborated by a post-hoc analysis cross-correlating the severity of NPS with gray matter loss across the whole PD group, which revealed that atrophy in the orbitofrontal cortex and frontal pole was specifically associated with elevated NPS.ConclusionsPrefrontal cortex atrophy in PD has an additional effect to dopamine replacement therapy on the generation of NPS in these patients. These findings are an important step towards the delineation of atrophy vs. neurochemical imbalance in PD, and the results emphasize the importance of considering interactions between prefrontal atrophy and neurochemical dysfunction in the genesis of neuropsychiatric symptoms in PD.     

Hippocampal volume and white matter disease in the prediction of dementia in Parkinson's disease

BackgroundLongitudinal neuroimaging studies could provide insights into pathophysiology of cognitive impairment in PD. We examined the role of hippocampal atrophy and cerebral white matter disease as risk factors for mild cognitive impairment and dementia in PD.MethodsProspective longitudinal study of patients with mild PD in a tertiary neurology center. All subjects underwent baseline MRI brain and had baseline and 6 monthly cognitive evaluations. Cognitive impairment was diagnosed based on the Movement Disorder Society Criteria. The predictive role of hippocampal volume and white matter hyperintensity at baseline on progression of cognitive impairment was studied.Results97 subjects with mean age 65.3 years, mean education of 10.3 years and mean Hoehn & Yahr of 1.9 were studied. Over 2 years, 16 subjects developed mild cognitive impairment and 8 subjects with mild cognitive impairment progressed to dementia. After adjusting for age and vascular risk factors, hippocampal volume was a significant predictor for mild cognitive impairment (OR 7.05, CI 1.5–34.1; p = 0.015) and dementia (OR 7.03, CI 2.39–25.2; p = 0.001). With Cox regression, hippocampal volume was a significant predictor for “time to cognitive impairment” (HR 7.67; CI 3.47–16.95, p < 0.001). Difference between survival curves based on volume of white matter hyperintensity in predicting “time to mild cognitive impairment” was significant (p = 0.0295).ConclusionsHippocampal volume is a major factor predicting the development of mild cognitive impairment and dementia in PD. White matter hyperintensity also contributes to the longitudinal cognitive status in PD.     

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders

Background

Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.

Objective

To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.

Methods

Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n₁ = 51, n₂ = 101), corticobasal degeneration (CBD) (n₁ = 11, n₂ = 3), progressive supranuclear palsy (PSP) (n₁ = 22, n₂ = 21), multiple system atrophy (MSA) (n₁ = 31, n₂ = 26), and healthy control (HC) (n₁ = 48, n₂ = 30) participants, as well as Alzheimer's disease (AD) (n₂ = 23) patients in the second cohort.

Results

Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021).

Conclusions

These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Chagas disease is independently associated with brain atrophy

Chagas disease (CD) remains a major cause of cardiomyopathy and stroke in developing countries. Brain involvement in CD has been attributed to left ventricular dysfunction, resulting in chronic brain ischemia due to hypoperfusion and/or embolic infarcts. However, cognitive impairment in CD may occur independently of cardiac disease. Therefore, we aimed to investigate head computed tomography (CT) findings in patients with Chagas disease cardiomyopathy (CDC) in comparison with other cardiomyopathies (OC). We studied 73 patients with CDC (n = 41) or OC (n = 32) matched for age and gender. These patients underwent head CT, rated by an investigator blinded to all clinical information. Head CT was rated for the presence of lacunar or territorial infarcts, as well as for measuring the total volumes of the brain, cerebellum and ventricles. Total brain volume was smaller in CDC as compared to OC patients (1,135 ± 150 vs. 1,332 ± 198 cm³, P < 0.001). Cerebellar and ventricular volumes did not differ between the groups. The prevalence of brain infarcts did not differ significantly between the groups. Chagas disease was the only independent predictor of brain atrophy in the multivariable analysis (OR = 1.38; 95% CI = 1.06–1.79, P = 0.017). Chagas disease is associated with brain atrophy independent of structural cardiac disease related to cardiomyopathy. Brain atrophy, rather than multiple infarcts, may represent the main anatomical substrate of cognitive impairment in Chagas disease.     

Voxel-based morphometry in unmedicated patients with restless legs syndrome

BackgroundThe pathophysiology of restless legs syndrome (RLS) is not yet understood. A prior voxel-based morphometry (VBM) study reported gray matter increase in the pulvinar of the thalamus in a group of patients, most of whom were on medical treatment. Since there is evidence that medication can change the volume of cerebral structures, the question arises as to whether the reported morphometric alterations are caused by the RLS itself or, alternatively, are a consequence of drug treatment. To address this issue, we performed VBM in unmedicated RLS patients.MethodsFourteen patients with idiopathic RLS with no (n = 11) or only minimal (n = 3) treatment exposure in the past and 14 age- and sex-matched healthy subjects were investigated. All subjects were free of psychotropic drugs for at least 4 months. Morphological data were analyzed by using optimized VBM.ResultsWe did not detect any structural changes except for slightly increased gray matter density in the ventral hippocampus (p = 0.046 on the left and p = 0.055 on the right side) and in the middle orbitofrontal gyrus (p = 0.046 on the right and p = 0.097 on the left side).ConclusionOur study could not confirm the findings of a prior study. A possible explanation for the divergent findings is the difference between the populations examined. Since, in our study, essentially treatment-naïve patients were investigated, it is possible that the prior findings reflect treatment-induced effects on cerebral morphology in RLS.     

Treatment of post-traumatic stress disorder in people with dementia: a structured literature review

Post-traumatic stress disorder (PTSD) is associated with cognitive dysfunctions and is an independent risk factor for dementia. A recent study has found the prevalence of PTSD in people with dementia is 4.7%–7.8%. However, little is known about the effectiveness of PTSD treatment for people with dementia. The primary aim of the current study is to review previous studies on the treatment of PTSD in people with dementia. A structured literature review was performed using a ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ analysis in PubMed, Embase, PsycINFO and CINAHL. Two independent researchers screened titles and abstracts. The inclusion criteria were: PTSD symptoms present, diagnosis of dementia, PTSD treatment form described and effects of the treatment mentioned. Articles that matched these criteria were included and content and quality were analyzed. We included nine articles, all case reports, with a total of 11 cases. The discussed treatment options are eye movement desensitisation and reprocessing (EMDR) (n = 3), prolonged exposure (n = 1), cognitive behavioural therapy (n = 1) and pharmacological treatment (n = 4). All articles reported a positive effect of the intervention on several monitored symptoms. Evidence for positive effects and feasibility of EMDR were most reliable, and it was applied in two articles of sufficient quality published in 2018 and 2019. EMDR ‘on-the-spot’ was described with positive effect in one article in which three cases were discussed. The quality of included papers ranged from insufficient to sufficient. This review shows that people with PTSD and dementia can benefit from PTSD treatment. EMDR, prolonged exposure, acceptance and commitment therapy and pharmacological treatment are applicable in this population. EMDR treatment is most described in this population (n = 5) and shows positive results, and the studies are of sufficient quality (n = 3). Further research in the form of a randomised controlled trial is required to study the effectivity of different treatment interventions in this population.