Letice Ericeira-Valente

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.

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.

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.

Long-term prognosis of geriatric major depression in relation to cognition and white matter integrity: follow up of two cases

INTRODUCTION: The geriatric depression (GD) represents one of the most frequent psychiatric disorders in outpatient services specialized in old-age treatment. OBJECTIVE: The course of two illustrative cases of GD is discussed, highlighting its clinical picture after antidepressant treatment and underlining variables related to disease prognosis, treatment effectiveness and conversion to major cognitive disorders such as vascular dementia (VD). METHODS: The cognitive performance, depressive symptoms, autonomy and brain structural measurements as white matter hyperintensities (WMH) and hippocampal size, and microstructural integrity of WM with diffusion tensor imaging were followed during four years. RESULTS: Case 1, with a severe degree of WMH, was associated with worsening cognition and increasing functional disability. Case 2, with mild WMH, an improvement of cognitive functioning could be seen. CONCLUSIONS: The existence of different subtypes of GD, as presented in this report, points a pathophysiological heterogeneity of GD, and suggests a possible continuum vascular depression (VaDp) and vascular cognitive impairment (VCI).

Behavioral and psychological symptoms and hippocampal atrophy in subcortical ischaemic vascular disease

Background Neuropsychiatric symptoms are common in patients with cognitive impairments, mediated by both neurodegenerative processes and cerebrovascular disease. Previous studies have reported that Behavioral and Psychological Symptoms of Dementia (BPSD) might correlate with severity of cognitive decline. Thus far, the impact of the association between white-matter hyperintensities (WHM) and hippocampal atrophy (HA) on the incidence of these symptoms has been less studied. Objective This cross-sectional study aimed to describe the clinical profile of a sample with large extensions of WMH, examining the association between different degrees of HA and cognitive, functional, and behavioral status. Methods Fifty outpatients (mean age: 76.86±8.70 years; 58% female; mean schooling: 7.44±4.69 years) with large extensions of WMH (modified-Fazekas scale=3) on MRI and different degrees of hippocampal atrophy (according to de Leon Score) underwent cognitive, functional, and behavioral assessments. Results Patients with mild-moderate to severe HA had worse performance on the Mini-Mental State Examination, Cambridge Cognitive Examination, Clinical Dementia Rating and Pfeffers Functional Activities Questionnaire, compared to the group with none or questionable HA. Appetite/Eating Behavior was the only cluster of neuropsychiatric symptoms associated with presence of HA in Vascular Cognitive Impairment patients. Discussion Although HA may exhibit distinct impact on cognitive performance and functional status, it appears to have little effect on behavioral symptoms in patients with high severity WMH.