Felipe Kenji Sudo

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.

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.

Structural Neuroimaging Findings in Major Depressive Disorder Throughout Aging: A Critical Systematic Review of Prospective Studies

Clinical manifestations of major depressive disorder (MDD) have been linked to structural and functional alterations in fronto-limbic circuits and white matter microstructural abnormalities. However, little is known about how brain pathological changes in volume and microstructure are related to illness progression throughout aging, including course deterioration and treatment response. A comprehensive review of the literature regarding midlife- and late-onset MDD was performed through PubMed/Medline, ISI, and EMBASE electronic databases from January 2000 to May 2014. Eligible references included prospective studies in which structural neuroimaging assessments were performed in MDD samples. The course of MDD may be associated with brain aging modifications, including hippocampal, amigdalar and frontal volume reductions. White matter changes associated with MDD progression have been reported in the corpus callosum, frontal and temporal regions and may be associated with poorer response to treatment. The data suggest that both cortical and subcortical alterations may interact along the progression of MDD. Further knowledge brought by neuroimaging studies, through the integration of multimodal techniques, may help to improve the accuracy of diagnosis, disease monitoring and treatment response in MDD.

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.

Neuroimaging findings related to behavioral disturbances in Alzheimer's disease: a systematic review.

BACKGROUND Behavioral and psychological symptoms of dementia (BPSD) associated with Alzheimers Disease (AD) have been linked to structural and functional alterations in fronto-temporal circuits and cortical abnormalities. However, little is known on how specific volumetric and functional brain changes may be associated with the frequency, severity and pattern of BPSD. METHODS A systematic review of the literature regarding neuroimaging and BPSD changes in AD was performed through Pubmed/Medline, ISI, and EMBASE electronic databases from January 2000 to May 2015. Eligible references (n=40) included clinical studies in which structural or functional neuroimaging assessment was performed in AD subjects presenting BPSD features. RESULTS BPSD symptoms, particularly apathy and psychosis have been associated in most of studies with either volume reductions or decreased metabolism in the prefrontal cortex (orbital and dorsolateral portions), anterior cingulate, insula and temporal lobes (middle portion). WM lacunes associated with AD progression have been associated with depressive symptoms. CONCLUSION The sum of evidence highlights the importance of BPSD-related imaging findings for the understanding of the non-cognitive symptom spectrum in AD. Results suggest that structural and functional changes in fronto-limbic areas may lead to emotional deregulation and symptom unawareness. As these findings may be present early on the AD clinical course, they may have a relevance for the development of imaging markers that could be used in diagnosis, disease monitoring and prediction of therapeutic response.

Metabolic Syndrome and cognitive decline in the elderly: A systematic review

Background Metabolic Syndrome (MetS) refers to a cluster of metabolic disturbances which is associated with increased risk for vascular and degenerative conditions in general population. Although the relationship between vascular risk factors and dementia is undisputable, additional hazard for cognitive decline in older population with concurrent metabolic disorders still waits to be demonstrated. The present review aims to analyze data on MetS and risk for cognitive decline in elderly persons. Methods Database searches were performed in Medline, ISI and PsycINFO for articles assessing cognitive performances of older subjects with MetS. Results Of a total of 505 studies, 25 were selected for the review. Risk of selection biases was identified in all the studies. Although all articles followed recognized diagnostic recommendations for MetS, minor criteria modifications were detected in most of them. Hyperglycemia was consistently associated with impaired cognitive performances in older individuals, but the role of MetS for cognitive decline and for the onset of dementia showed heterogeneous results. Discussion Current available data in the literature concerning the impact of MetS on the cognition of older population is inconclusive and based on inconsistent evidence. Differential effects of individual MetS components and factors associated with the age of the sample may have accounted for divergent findings among articles, but larger and higher quality studies in this field are still needed.

Financial capacity in dementia: a systematic review

ABSTRACT Objectives: Financial capacity (FC) refers to a set of cognitively mediated abilities related to ones competency to manage propriety and income. Identifying intact from impaired FC in older persons with dementia is a growing concern in geriatric practice, but the best methods to assess this function still need to be determined. This study aims to review data on FC in dementia and on instruments used to assess this domain of capacity. Methods: Database search was performed in Medline, ISI Web of Knowledge, LILACS and PsycINFO. Studies that objectively assessed FC in dementia of any etiology were included. Results: Of a total of 125 articles, 10 were included. Mild Alzheimers Disease (AD) was associated with impaired complex FC abilities, namely checkbook management, bank statement management and financial judgment, but simple FC skills were preserved. Moderate AD was associated with impairment in all domains of FC. The Financial Capacity Instrument (FCI) was applied in most of the selected studies and correlated with neuropsychological and neuroimaging variables. Conclusions: Early dementia is associated with partially preserved FC. More validation studies using objective and evidence-based FC assessment tools, such as the FCI, are still needed.