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.

Vascular mild cognitive impairment (VaMCI) represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction.MethodsTwenty-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.ResultsVaMCI 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.ConclusionExtension 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.

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ObjectiveNon-amnestic dysexecutive Vascular Mild Cognitive Impairment (VaMCI) may represent preclinical Vascular Dementia (VaD). The aim of this study was to summarize the clinical, neuropsychological and neuroimaging aspects of VaMCI; and to assess its patterns of progression to dementia.MethodsSearches were made in the ISI Web of Knowledge, PubMed and Lilacs databases, using the terms "mild cognitive impairment" and "executive function". Altogether, 944 articles were retrieved.ResultsVaMCI cases had poorer performances on fronto-executive tasks, a higher prevalence of stroke, presence of periventricular and profound white matter hyperintensities on MRI images, as well as more extrapyramidal signs and behavioral symptoms. Executive dysfunction might be associated with disconnection of fronto-parietal-subcortical circuits. Progression to dementia was associated with baseline deficits in executive function, in simple sustained attention and language, and large periventricular WMH.DiscussionVaMCI develops with impairment in non-memory domains and subcortical white matter changes on MRI images, which are consistent with clinical and neuroimaging findings in VaD.

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BackgroundNeuropsychiatric 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.ObjectiveThis 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.MethodsFifty 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.ResultsPatients with mild-moderate to severe HA had worse performance on the Mini-Mental State Examination, Cambridge Cognitive Examination, Clinical Dementia Rating and Pfeffer's 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.DiscussionAlthough 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.

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.

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