Roberta Rossi

A comparison between the accuracy of voxel-based morphometry and hippocampal volumetry in Alzheimer's disease

To compare the accuracy of voxel‐based morphometry (VBM) and region of interest (ROI)‐based hippocampal volumetry to detect medial temporal lobe atrophy in Alzheimers disease (AD).

Brain anatomy of persistent violent offenders: More rather than less

Most violent crimes in Western societies are committed by a small group of men who display antisocial behavior from an early age that remains stable across the life-span. It is not known if these men display abnormal brain structure. We compared regional brain volumes of 26 persistently violent offenders with antisocial personality disorder and substance dependence and 25 healthy men using magnetic resonance imaging volumetry and voxel-based morphometry (VBM). The violent offenders, as compared with the healthy men, had markedly larger white matter volumes, bilaterally, in the occipital and parietal lobes, and in the left cerebellum, and larger grey matter volume in right cerebellum (effect sizes up to 1.24, P<0.001). Among the offenders, volumes of these areas were not associated with psychopathy scores, substance abuse, psychotropic medication, or global IQ scores. By contrast, VBM analyses of grey matter revealed focal, symmetrical, bilateral areas of atrophy in the postcentral gyri, frontopolar cortex, and orbitofrontal cortex among the offenders as compared with the healthy men (z-scores as high as 5.06). Offenders with psychopathy showed the smallest volumes in these areas. The larger volumes in posterior brain areas may reflect atypical neurodevelopmental processes that underlie early-onset persistent antisocial and aggressive behavior.

MRI of hippocampus and entorhinal cortex in mild cognitive impairment: A follow-up study

The concept of mild cognitive impairment (MCI) has been proposed to represent a transitional stage between normal aging and dementia. We studied the predictive value of the MRI-derived volumes of medial temporal lobe (MTL) structures, white matter lesions (WML), neuropsychological tests, and Apolipoprotein E (APOE) genotype on conversion of MCI to dementia and AD. The study included 60 subjects with MCI identified from population cohorts. During the mean follow-up period of 34 months, 13 patients had progressed to dementia (9 to Alzheimers disease (AD)). In Cox regression analysis the baseline volumes of the right hippocampus, the right entorhinal cortex and CDR sum of boxes predicted the progression of MCI to dementia during the follow-up. In a bivariate analysis, only the baseline volumes of entorhinal cortex predicted conversion of MCI to AD. The Mini-Mental State Examination (MMSE) score at baseline, WML load, or APOE genotype were not significant predictors of progression. The MTL volumetry helps in identifying among the MCI subjects a group, which is at high risk for developing AD.

Frontotemporal dementia as a neural system disease

Some brain structures atrophic in frontotemporal dementia (FTD) belong to the rostral limbic system (RLS), that regulates context-dependent behaviors after evaluation of the motivational content of stimuli. The clinical manifestations of FTD are consistent with its impairment. Aim of this study was to assess whole brain morphology in FTD using magnetic resonance imaging (MRI) and voxel-based morphometry with statistic parametric mapping (SPM99) to test the hypothesis that the RLS might be specifically targeted by FTD. Nine FTD patients and 26 healthy controls underwent high resolution 3D MRI. SPM99 performed (a) spatial normalization to a customized template, (b) segmentation, (c) smoothing, (d) voxel-by-voxel comparison of gray matter between cases and controls. P was set at 0.05 corrected for multiple comparisons. All but one regions of the RLS (the periaqueductal gray) were atrophic in FTD. At P<0.001 uncorrected also the periaqueductal gray was atrophic. Atrophy outside the RLS was confined to a few voxels in the frontal and temporal gyri. FTD might be a neural-system disease where the RLS is predominantly damaged.

Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment

Background: The diagnosis of mild cognitive impairment (MCI) is clinically unhelpful, as many patients with MCI develop dementia but many do not. Objective: To identify clinical instruments easily applicable in the clinical routine that might be useful to predict progression to dementia in patients with MCI assessed in the outpatient facility of a memory clinic. Participants and methods: 52 dementia-free patients (mean (standard deviation) age 70 (6) years; 56% women) with MCI, and 65 healthy controls (age 69 (6) years; 54% women) underwent brain magnetic resonance scan with standardised visual assessment of medial temporal atrophy (MTA) and subcortical cerebrovascular lesions (SVLs). Follow-up assessment occurred 15.4 (SD 3.4) months after baseline to detect incident dementia and improvement, defined as normal neuropsychological performance on follow-up. Results: Patients were classified into three groups according to the presence of memory disturbance only (MCI Mem), other neuropsychological deficits (MCI Oth) or both (MCI Mem+). MCI Mem and Mem+ showed MTA more frequently (31% and 47% v 5% and 14% of controls and MCI Oth, p<0.001). 11 patients developed dementia (annual rate 16.5%) and 7 improved on follow-up. The only independent predictor of progression was MTA (odds ratio (OR) 7.1, 95% confidence interval (CI) 1.4 to 35.0), whereas predictors of improvement were the absence of memory impairment (OR 18.5, 95% CI 2.0 to 171.3) and normal MRI scan (OR 10.0, 95% CI 1.7 to 60.2). Conclusion: Neuropsychological patterns identify groups of patients with MCI showing specific clinical features and risk of progression to dementia. MTA clinically rated with a visual scale is the most relevant predictor of progression and improvement.

Alexithymia in healthy women: A brain morphology study

BACKGROUND Alexithymia relates to difficulty recognizing and describing own feelings. Recent literature shows that specific structures process emotions. Aim of this study was to investigate whether alexithymia is associated with a specific cerebral morphology of candidate structures in healthy adults. METHODS Fifty-four female volunteers were enrolled in the study and the 20-item Toronto Alexithymia Scale (TAS-20) was self-administered. Gray matter (GM) volume was assessed with an optimized voxel-based morphometry (VBM) protocol on high-resolution 3D magnetic resonance images. The following three experiments were carried out: 1) contrast between the 14 volunteers with TAS-20 scores > or = 61 (alexithymic) and the 30 with scores < 51 (non-alexithymic), 2) correlation of TAS-20 scores on the whole sample and 3) contrast between the 14 alexithymic and 14 non-alexithymic matched by age. The significant threshold for VBM comparisons and correlation was set at p<0.005 uncorrected. RESULTS The alexithymic group showed smaller GM volume in the anterior cingulate cortex (cluster size: 735 voxel no.; z=3.26; stereotaxic coordinates: -12, 22, 30) and middle temporal gyrus (256; 3.21; -60, 2, -20). Of specific biological relevance, smaller clusters were located in the anterior insula, orbitofrontal cortex and superior temporal sulcus. The opposite comparison was negative. The correlation analysis confirmed the pattern of results mainly in the left hemisphere. CONCLUSIONS Our findings suggest that the ability to process emotional aspects of the self correlates with morphology of a specific set of cerebral structures known to be involved in decision making and self awareness and rich in neurons subserving social competence.

Abnormal hippocampal shape in offenders with psychopathy

Posterior hippocampal volumes correlate negatively with the severity of psychopathy, but local morphological features are unknown. The aim of this study was to investigate hippocampal morphology in habitually violent offenders having psychopathy. Manual tracings of hippocampi from magnetic resonance images of 26 offenders (age: 32.5 ± 8.4), with different degrees of psychopathy (12 high, 14 medium psychopathy based on the Psychopathy Checklist Revised), and 25 healthy controls (age: 34.6 ± 10.8) were used for statistical modelling of local changes with a surface‐based radial distance mapping method. Both offenders and controls had similar hippocampal volume and asymmetry ratios. Local analysis showed that the high psychopathy group had a significant depression along the longitudinal hippocampal axis, on both the dorsal and ventral aspects, when compared with the healthy controls and the medium psychopathy group. The opposite comparison revealed abnormal enlargement of the lateral borders in both the right and left hippocampi of both high and medium psychopathy groups versus controls, throughout CA1, CA2‐3 and the subicular regions. These enlargement and reduction effects survived statistical correction for multiple comparisons in the main contrast (26 offenders vs. 25 controls) and in most subgroup comparisons. A statistical check excluded a possible confounding effect from amphetamine and polysubstance abuse. These results indicate that habitually violent offenders exhibit a specific abnormal hippocampal morphology, in the absence of total gray matter volume changes, that may relate to different autonomic modulation and abnormal fear‐conditioning. Hum Brain Mapp, 2010.

Visual assessment of medial temporal atrophy on MR films in Alzheimer’s disease: comparison with volumetry

Background and aims: To test the agreement of a visual rating scale of medial temporal lobe atrophy (MTA) with linear and volumetric assessments, and to test its accuracy in discriminating between Alzheimer’s disease (AD) patients and controls. Methods: Participants were 28 patients with AD and 29 healthy controls. MTA was evaluated according to Scheltens’ five-point scale. Its accuracy in distinguishing AD patients from controls was evaluated as a stand-alone measure and in association with linear [width of the temporal horn (WTH)] and volumetric [hippocampal volume (HV)] measures. Results: The agreement of this visual rating scale with the other MTA measures was statistically significant (vs WTH and vs HV, p for trend <0.00005). The visual rating scale showed a good accuracy in distinguishing AD patients from controls [area under the curve (AUC) 0.89, 95% confidence interval (CI) 0.79-0.98]. Although the accuracy of the visual rating scale improved in association with linear WTH (AUC 0.91, 95% CI 0.82–0.99) and in association with HV (AUC 0.93, 95% CI 0.86–1.00), the improvement was not significant. Conclusions: The visual rating scale of MTA, easily applicable in clinical practice, shows good agreement with more demanding quantitative methods, and can discriminate AD patients from controls with good accuracy.

Long-acting antipsychotic drugs for the treatment of schizophrenia: use in daily practice from naturalistic observations.

BackgroundCurrent guidelines suggest specific criteria for oral or long-acting injectable antipsychotic drugs (LAIs). This review aims to describe the demographic and clinical characteristics of the ideal profile of the patient with schizophrenia treated with LAIs, through the analysis of nonrandomized studies.MethodsA systematic review of nonrandomized studies in English was performed attempting to analyze the factors related to the choice and use of LAIs in daily practice. The contents were outlined using the Cochrane methods for nonrandomized studies and the variables included demographic as well as clinical characteristics. The available literature did not allow any statistical analysis that could be used to identify the ideal profile of patients with schizophrenia to be treated with LAIs.ResultsEighty publications were selected and reviewed. Prevalence of LAI use ranged from 4.8% to 66%. The only demographic characteristics that were consistently assessed through retrieved studies were age (38.5 years in the 1970’s, 35.8 years in the 1980’s, 39.3 years in the 1990’s, to 39.5 years in the 2000’s) and gender (male > female).Efficacy was assessed through the use of various symptom scales and other indirect measurements; safety was assessed through extrapyramidal symptoms and the use of anticholinergic drugs, but these data were inconsistent and impossible to pool. Efficacy and safety results reported in the different studies yielded a good therapeutic profile with a maximum of 74% decrease in hospital admissions and the prevalence of extrapyramidal symptoms with LAIs consistently increased at 6, 12, 18, and 24 months (35.4%, 37.1%, 36.9%, and 41.3%, respectively).ConclusionsThis analysis of the available literature strongly suggests that further observational studies on patients with schizophrenia treated with LAIs are needed to systematically assess their demographic and clinical characteristics and the relationships between them and patient outcome.Besides the good efficacy and safety profile of LAIs, health care staff must also take into account the importance of establishing a therapeutic alliance with the patient and his/her relatives when selecting the most appropriate treatment. LAIs seem to be a good choice not only because of their good safety and efficacy profile, but also because they improve compliance, a key factor to improving adherence and to establishing a therapeutic alliance between patients with schizophrenia, their relatives, and their health care providers.

Structural brain features of borderline personality and bipolar disorders

A potential overlap between bipolar disorder (BD) and borderline personality disorder (BPD) has been recently proposed. We aimed to assess similarities and differences of brain structural features in BD and BPD. Structural magnetic resonance imaging (MRI) was performed in 26 inpatients with BPD, 14 with BD, and 40 age-and sex-matched healthycontrols (HC). Voxel-based morphometry analysis with Statistical Parametric Mapping (SPM) was used to localize and quantify gray (GM) and white matter (WM) abnormalities in BD and BPD compared to HC and to identify those specifically affected in each patient group. Region of interest (ROI)-based analyses were also performed for confirmation. GM density changes in BD are significantly more diffuse and severe than in BPD, as demonstrated in both SPM- and ROI-based analyses. The topography of GM alterations showed some regions of overlap, but each disorder had specific regions of abnormality (involving both cortical and subcortical structures in BD, confined mainly to fronto-limbic regions in BPD). WM density changes were less pronounced in both conditions and involved completely different regions. Although BPD and BD show a considerable overlap of GM changes, the topography of alterations is more consistent with the separate conditions hypothesis and with the vulnerability of separate neural systems.