Cristina Testa

Detection of grey matter loss in mild Alzheimer's disease with voxel based morphometry

Objectives: To test the applicability of an automated method of magnetic resonance image analysis (voxel based morphometry) to detect presence and severity of regional grey matter density reduction—a proxy of atrophy—in Alzheimers disease. Methods: Twenty nine probable Alzheimers patients and 26 non-demented controls (mini-mental state examinations mean (SD) 21 (4) and 29 (1)) underwent high resolution 3D brain magnetic resonance imaging. Spatial normalisation to a stereotactic template, segmentation into grey matter, white matter, and cerebrospinal fluid, and smoothing of the grey matter were carried out based on statistical parametric mapping (SPM99) algorithms. Analyses were carried out: (a) contrasting all Alzheimers patients with all controls (p<0.05 corrected for multiple comparisons); (b) contrasting the three Alzheimers patients with mini-mental state of 26 and higher with all controls (p<0.0001 uncorrected); and (c) correlating grey matter density with mini-mental state score within the Alzheimers group (p<0.0001 uncorrected). Results: When all Alzheimers patients were compared with controls, the largest atrophic regions corresponded to the right and left hippocampal/amygdalar complex. All parts of the hippocampus (head, body, and tail) were affected. More localised atrophic regions were in the temporal and cingulate gyri, precuneus, insular cortex, caudate nucleus, and frontal cortex. When the mildest Alzheimers patients were contrasted with controls, the hippocampal/amygdalar complex were again found significantly atrophic bilaterally. The mini-mental state score correlated with grey matter density reduction in the temporal and posterior cingulate gyri, and precuneus, mainly to the right. Conclusions: Voxel based morphometry with statistical parametric mapping is sensitive to regional grey matter density reduction in mild Alzheimers disease.

A voxel based morphometry study on mild cognitive impairment

Background: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer’s disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. Objective: To study the pattern of brain atrophy in MCI. Methods: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p<0.001. Results: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere—for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. Conclusions: The MRI findings in MCI resemble those seen in early AD.

Structural correlates of early and late onset Alzheimer’s disease: voxel based morphometric study

Objective: To examine the brain structural correlates of age at onset in patients with Alzheimer’s disease. Methods: We studied nine patients with early onset (age ⩽65 years), nine with late onset (age >65) Alzheimer’s disease (EOAD and LOAD, respectively) of mild-moderate severity, and 26 controls who were stratified into younger (YC, age ⩽65, n = 9) and older (OC, age >65, n = 17) subjects. The patients were closely matched for clinical severity: 3/2/3/1 patients had clinical dementia rating of 0.5/1/2/3, respectively, in both the groups. High resolution magnetic resonance images of the brain of the EOAD and YC groups and the LOAD and OC groups were compared on a voxel by voxel basis with statistical parametric mapping to detect areas specifically atrophic. Results: The patients with EOAD showed greater neocortical atrophy at the temporoparietal junction while the patients with LOAD showed greater hippocampal atrophy. The results could not be accounted for by the apolipoprotein E genotype. Conclusions: Since genetic factors are believed to play a relevant pathogenetic role in EOAD and environmental factors in LOAD, genetic and environmental factors may differentially predispose the neocortical and limbic areas to the development of Alzheimer’s neuropathology.

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.

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.

Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment

ObjectiveAim of this study was to find cerebral perfusion correlates of conversion to dementia in patients with amnestic MCI.Methods17 healthy subjects (age = 69 ± 3, 9 females), and 23 amnestic MCI patients (age = 70 ± 6, 10 females) underwent brain MR scan and 99mTc ECD SPECT. Conversion to AD was ascertained on average 19 ± 10 months after baseline: 9 had converted (age = 69 ± 3, 4 females), and 14 had not (age = 71 ± 8, 6 females). We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls. We assessed the effect of gray matter atrophy on the above results with SPM2 using an optimized Voxel-Based Morphometry (VBM) protocol.We compared significant hypoperfusion with significant atrophy on a voxel-byvoxel basis.ResultsIn comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and left inferior temporal and fusiform gyri,whereas those who did not convert showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side.We found no overlap between significant atrophy and significant hypoperfusion regions.ConclusionsParahippocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a correlate of conversion to AD; hypoperfusion in the retrosplenial cortex is involved in memory impairment but does not seem the key prognostic indicator of conversion to dementia.

Cerebral magnetic resonance imaging reveals marked abnormalities of brain tissue density in patients with cirrhosis without overt hepatic encephalopathy

BACKGROUND & AIMS We applied advanced magnetic resonance imaging and Voxed based Morphometry analysis to assess brain tissue density in patients with cirrhosis. METHODS Forty eight patients with cirrhosis without overt hepatic encephalopathy (17 Child A, 13 Child B, and 18 Child C) and 51 healthy subjects were matched for age and sex. Seventeen patients had history of overt hepatic encephalopathy, eight of them had minimal hepatic encephalopathy at inclusion, 10 other patients had minimal hepatic encephalopathy at inclusion but without history of previous overt hepatic encephalopathy, and 21 patients had none of these features. RESULTS Patients with cirrhosis presented decreased brain density in many areas of the grey and white matter. The extension and size of the affected areas were greater in patients with alcoholic cirrhosis than in those with post-hepatitic cirrhosis and correlated directly with the degree of liver failure and cerebral dysfunction (as estimated by neuropsychological tests and the antecedent of overt hepatic encephalopathy). Twelve additional patients with cirrhosis who underwent liver transplantation were explored after a median time of 11months (7-50months) after liver transplant. At the time of liver transplantation, three patients belonged to class A of the Child-Pugh classification, five to class B and four to class C. Compared to healthy subjects, liver transplant patients showed areas of reduced brain density in both grey and white matter. CONCLUSIONS These results indicate that loss of brain tissue density is common in cirrhosis, progresses during the course of the disease, is greater in patients with history of hepatic encephalopathy, and persists after liver transplantation. The significance, physiopathology, and clinical relevance of this abnormality cannot be ascertained from the current study.

Effects of hormone therapy on brain morphology of healthy postmenopausal women : a Voxel-based morphometry study

Objective: Estrogens are known to be protective in age-associated cognitive changes in humans and in neurodegeneration in animal models. The aim of this study was to evaluate the potential effects of estrogen therapy (ET) on human gray matter volume in vivo. Design: Forty healthy postmenopausal women underwent three-dimensional high-resolution magnetic resonance imaging: 17 were never treated, 16 were currently receiving ET, and 7 had had ET in the past. Voxel-based morphometry (VBM) with SPM2 was used, according to an optimized protocol, to compare women under past and current ET to those never treated. Significance threshold was set at P = 0.01, corrected by false discovery rate. Results: Voxel-based morphometry indicated that estrogen use was associated with greater gray matter volumes in the whole group of treated women, which included the cerebellum (cluster size, Z coordinates: 5,527; 5.15; −14 −54 −10), the amygdaloid-hippocampal complex (left: 19; 3.55; −22 −4 −18; right: 45; 3.61; 16 −6 −16), and extended to the frontal, temporal, parietal, and occipital neocortex. The comparison current ET versus past ET use showed that women who underwent treatment in the past had greater volumes of gray matter compared to women under current treatment. Conclusions: ET might slow down age-related gray matter loss in postmenopausal women. The structures that exhibited greater volume in association with ET included the cerebellar and cerebral cortices and, typically involved in Alzheimers disease, the medial temporal structures and the temporoparietal junction.