Carlos Eduardo de Oliveira Alves

Different Patterns of White Matter Degeneration Using Multiple Diffusion Indices and Volumetric Data in Mild Cognitive Impairment and Alzheimer Patients

Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.

Cognitive disconnective syndrome by single strategic strokes in vascular dementia

Strategic regions correspond to associative, limbic and paralimbic structures and related circuits, that underpin cognitive/behavioral functions. Strokes in these eloquent sites produce pictures of vascular dementia with syndromic features due to specific site lesion and/or interruption of their interconnections. This study aims at analysing subcortical strategic strokes that express similar cognitive/behavioral elements, by sharing common pathways. Patients (n=6) who attended in specialized ambulatory, were submitted to neuropsychological and neuroimaging assessments through MRI (GE Signa Horizon 1.5T) and brain SPECT (Millennium MG, ECD [TC-99m]). Stroke locations and respective main symptoms were: 1. anteromedian thalamus [L]: anterograde and retrograde amnesia (ARA), expression aphasia (EA), executive dysfunction (ED), apathy, and depression; 2. anterior thalamus [R]: ARA, inattention, apathy, and aggressiveness; 3. dorsomedian thalamus [L]: inattention, ED, anosognosia, and aggressiveness; 4. central paramedian thalamus [R]: EA, visual perception deficits (VPD), ED, infantility, and personality disorder; 5. caudate nucleus (ventral-head) [L]: VPD, ED, delirium, visual hallucinations, and personality disorder; and 6. anterior capsule [L]: VPD, ED, apathy, and depression. Vascular strategic syndromes connote the predominantly impaired cognitive/behavioral symptom of each site. Temporal and frontal disconnection symptoms were produced by disrupted MTT/hippocampal and IML/amygdala circuits expressing amnesic syndrome associated with heterogeneous dysexecutive syndrome, in all the cases, by disrupting frontal-basal ganglia-thalamus-cortical net, in three different levels of their pathway.

Clinical characteristics in subcortical ischemic white matter disease

BACKGROUND Vascular white matter lesions (WML) represent one of the main neuroimage findings in individuals older than 65 years and its clinical significance is still partially understood. OBJECTIVE To describe and analyze the clinical profile of a high severity sample with WML focusing on the frontal executive control. METHOD Outpatients (n=20) with high severity WML evaluated with magnetic resonance imaging were selected using the Fazekas scale. RESULTS Most patients (n=17; 85%) presented an altered Trail Making Test ratio (section B/section A); on verbal fluency, 15 individuals (75%) performed below the cutoff score. Apathy (5.9 +/- 4.65) and depression (3.05+/-3.67) were frequent as assessed by the Neuropsychiatric Inventory. The impairment in functional activities strongly correlated with apathy (r=0.814, p<0.001) and verbal fluency (r=0.744, p<0.001). CONCLUSION Executive dysfunction, apathy, and ratio depression were the main characteristics found. Extension of WML may have distinct impact on the clinical picture, but further studies with methodological adjustments are necessary to provide more definitive conclusions.

White matter hyperintensities, executive function and global cognitive performance in vascular mild cognitive impairment

UNLABELLED Vascular mild cognitive impairment (VaMCI) represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction. METHODS Twenty-six individuals (age: 73.11±7.90 years; 65.4% female; schooling: 9.84±3.61 years) were selected through neuropsychological assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals (n=15) were compared to normal controls (NC, n=11) and correlated with Fazekas scale. RESULTS VaMCI performed significantly worse than NC in Trail-Making Test (TMT) B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination (CAMCOG) final scores. Correlations were found among scores in modified Fazekas scale and performances in TMT B (time to complete and errors), difference TMT B-A and CAMCOG total score. CONCLUSION Extension of white matter hyperintensities might be correlated to poorer global cognition and impairments in a set of fronto-executive functions, such as cognitive speed, set shifting and inhibitory control in VaMCI.

Subcortical ischemic vascular disease and cognition. A systematic review

Subcortical Ischemic Vascular Disease (SIVD) is underdiagnosed. This review investigates the relationship among SIVD severity, cognitive status and neuroimaging markers. Methods Cohort, cross-sectional and case control studies were searched on ISI, Medline, Scielo, PsychoInfo and LILACS databases published between 1995 and 2006. Results The most impaired cognitive domains were executive, attentional and memory retrieval mechanisms. These cognitive features were frequently associated to White Matter Lesions (WML). Conclusions WML is an independent factor in cognitive decline. However, the threshold for this impact is not yet clearly established.

Binswanger's disease and quantitative fractional anisotropy

OBJECTIVE To study the integrity of the white matter in Binswangers disease (BD) patients with quantitative fractional anisotropy (DTI-FA). METHOD Controls (12) and patients with BD (12) were included. Scans performed with MR (GE Signa Horizon/1.5T). Fazekass score=6 with white matter hyperintensities extension >75% assessed on FLAIR scans. Standard parameters for DTI-FA were used. ROIs placed in symmetrical regions on two axial planes, data pooled in anterior (frontal) and posterior (temporo-parieto-occipital) regions. Analysis with Functool. Statistics for anterior and posterior regions comparison. RESULTS DTI-FA showed reduction of anisotropy, reflecting axonal damage and demyelination of fibers, more prominent in anterior in relation to posterior region, in BD patients in comparison to controls. CONCLUSION Loss of integrity of fiber tracts reflects interruption of neural networks that subserve cognitive, behavioral, and motor integration. The more severely affected frontal region is related to executive dysfunction, a characteristic feature of Binswangers disease.

Vascular dementia by thalamic strategic infarct

. The thalamic nuclei may be classified in five functional classes and include associative and limbic ones. Branches from the posterior cerebral cir-culation supply different nuclear groups and intrathalam-ic tract fibers. The syndromes may be classified consider-ing functional characteristics of the damaged nuclei and the affected vascular territories

Diffusion tensor imaging studies in vascular disease. A review of the literature

Cerebrovascular disease (CVD) is often present in old age and may be associated with microstructural pathology of white matter (WM) and cognitive dysfunction. The current review investigated the relationship between CVD, cognitive status and WM integrity as assessed by diffusion tensor imaging (DTI). Methods DTI studies were searched on ISI and Pubmed databases from 2002 to 2012. Results Studies evidenced DTI changes in WM as associated with vascular disease and provide increasing support for DTI as a valuable method for early detection of CVD. Conclusion DTI parameters can serve as important biomarkers in monitoring vascular disease progression and treatment response and may represent a surrogate marker of WM tract integrity.

Executive testing predicts functional loss in subjects with white matter lesions

In order to assess ecological validity of executive function (EF) tests and the impact of EF dysfunction on functional status in elderly subjects with moderate and severe subcortical white matter hyperintensities (WMHs), we made a correlation analysis between EF scores and two measures of Instrumental Activities of Daily Living (IADL). Trail-making test and CLOX correlated with the ability to perform IADL in subjects with severe WMH. EF tests might present low ecological validity for those with WMH below severe stage.

The corpus callosum in Binswanger's disease: A quantitative fractional anisotropy analysis

To study the integrity of the corpus callosum in Binswanger’s disease (BD) patients using quantitative fractional anisotropy (DTI-FA). Methods Controls (12) and patients with BD (12) were included. MR [GE Signa Horizon-1.5T] scans were performed. BD patients presented Fazekas’s score=6 and leukoaraiosis extension =75%, as assessed on FLAIR sequence. Standard parameters for DTI-FA acquisition were used. Functool was employed for post-processing, and ROIs placed on the genu and splenium of the corpus callosum on one axial plane at the basal ganglia level. Statistics [ANOVA] for genu and splenium comparison were analyzed. Results DTI-FA showed reduction of anisotropy in both regions of the corpus callosum, more prominently in anterior (genu) than posterior (splenium) in BD patients versus controls. Conclusion The reduction of anisotropy reflects loss of integrity of fibers of the studied regions of the corpus callosum. This finding indicates an interruption of the most important inter-hemispheric commissure, and component of neural networks that underlies cognitive, behavioral, motor and sensory integration. The affected genu and splenium, together with damage to other fiber systems that connect the prefrontal and parietal-occipital regions, may manifest clinically as dysfunction of high-level integrative regions linked to the domains of executive and sensory functions, respectively, that can occur in Binswanger’s disease.