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Leukoaraiosis is one of the main contributors to mild cognitive impairment due to vascular damage (vascular MCI, VMCI), whose pathophysiology has not been fully elucidated yet. We aimed to shed light on such issue using functional MRI (fMRI). Sixteen patients with VMCI were enrolled and compared with twenty-five patients with MCI but without significant vascular damage (non-vascular MCI, NVMCI) and with fifteen healthy controls (HC). They all underwent fMRI with incidental verbal learning paradigm, using a 3T scanner. Differently from cases with NVMCI (versus HC), VMCI patients presented a higher BOLD activation in the right parieto-occipital cortex and a lower activation in the left superior and middle frontal gyri, anterior cingulum and in left fronto-opercular area when compared to HC. Cortical activation evaluated by fMRI may reflect specific patterns of damage and attempt of compensation in patients with MCI and different severity of leukoaraiosis., (Copyright © 2018. Published by Elsevier B.V.)

Leukoaraiosis, also referred to as white-matter hyperintensities (WMHs) or age-related white matter changes, is the most frequently seen lesion on brain magnetic resonance images (MRI) in the elderly. LA is a subject of intense research interest, and is correlated with stroke, cognitive impairment or dementia, disturbances, affective disorders, and poor prognoses. Rapid advances in neuroimaging have enabled greater understanding of LA associated with aging-related cognitive decline or dementia. Recently, the techniques of multimodal MRI, such as structural MRI (sMRI), resting-state functional MRI (rs-MRI), cerebrovascular reactivity (CVR), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and dynamic contrast-enhanced MRI (DCE-MRI), have been used to explore the underlying mechanism of cognitive impairment in patients with LA. These multimodal MRI techniques may provide further insights into the structural and functional changes of LA with cognitive dysfunction.

Background: Leukoaraiosis and its progression have longitudinally been associated with cognitive decline and dementia. Its role in acute cognitive function and response to acute cerebral ischemia is less well understood. We evaluated whether the presence and extent of leukoaraiosis, or white matter hyperintensities (WMH), had an impact on performance on tests of hemispatial neglect in acute ischemic stroke patients., Methods: A series of 206 acute ischemic right-hemispheric stroke patients at Johns Hopkins Hospital underwent brain MRI and cognitive assessment for hemispatial neglect within 5 days of symptom onset. Error rates on neglect tests were evaluated, as were dichotomized measures of neglect, including 'any', 'severe' or 'worst' neglect, based on Z scores of at least 2 on 1, 2 or 3 tests (respectively) within a neglect battery. Acute infarct volumes were measured on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery images were reviewed for WMH, using the Cardiovascular Health Study (CHS) rating scale (ranging from 0 to 9, with 9 being 'most extensive'). Linear regression was used to evaluate 'error rate on neglect test' as the dependent variable, as a measure of neglect severity, with 'WMH category' as the primary independent variable, including adjustment for age, sex, race and infarct volume (on DWI). Logistic regression was used to evaluate a binary definition of neglect (defined as above) relative to the same independent variable and covariates., Results: Each 1-point increase in CHS leukoaraiosis category was associated with 1.20-fold increased odds (95% CI: 1.00-1.43) of having any neglect, 1.23-fold increased odds (95% CI: 1.02-1.49) of having severe neglect and 1.33-fold increased odds of having worst neglect (95% CI: 1.01-1.76) after adjusting for infarct volume, age, sex and race. Increasing age and infarct size were also important predictors of neglect severity, with a 2.36% higher error rate (95% CI: 0.75-3.97%) on the line cancellation test associated with each category increase in CHS score; similar results were found for each of the neglect tests. Line cancellation neglect scores were worse in individuals with both severe WMH and large infarcts (p interaction, unadjusted=0.03)., Conclusions: More severe leukoaraiosis is associated with more hemispatial neglect after acute ischemic stroke, independent of infarct volume, age and sex. We found not only more frequent neglect but also more severe neglect, based on error rates on neglect tests, in individuals with increasing leukoaraiosis. This emphasizes the importance of preexisting brain microvascular disease in outcomes of stroke patients. Further studies of the possible mechanism behind this association are needed., (© 2014 S. Karger AG, Basel.)

Background and Purpose: Leukoaraiosis (LA) might interrupt intra- and interhemispheric communication and thus induce cognitive impairments and dementia. It remains unclear, however, if there is a volume threshold of LA that is needed before either the signs of dementia and/or a specific pattern of neuropsychological impairment become manifest. Roman et al has suggested that 25% of white matter may need to be involved before white matter alterations influence the clinical signs associated with dementia. The purpose of this study is to ascertain the threshold of MRI-LA as measured with a visual rating scale needed to induce specific patterns of neuropsychological impairment associated with dementia., Methods: One hundred fifteen patients with dementia received a comprehensive neuropsychological examination and the severity of MRI-LA was measured using a 40-point LA scale., Results: Patients were categorized into low (mean LA=4.21+/-2.92; 3.22%-17.82%), moderate (mean LA=12.58+/-2.54; 25.01%-37.80%), and severe (mean LA=22.36+/-4.04; 45.80%-66.00%) LA groups. Patients in the mild LA group obtained markedly lower scores on tests of episodic memory compared with working memory, a neuropsychological profile often associated with Alzheimer disease. Patients with moderate LA displayed equal impairment on neuropsychological tests. Patients in the severe LA group obtained significantly lower scores on tests of working memory as compared with episodic memory., Conclusions: These data provide evidence that a threshold of moderate MRI-LA as measured with a visual rating scale is associated with greater and/or equal impairment on tests of working memory versus episodic memory and provides a benchmark to assess the effect of MRI-LA on the clinical presentation of dementia.

Background and Purpose: Associations between regional white matter lesion pathology and neuropsychological performance across the aging spectrum are not well understood and, to date, research has been largely contradictory and inconclusive. The current study set out to clarify some of the inconsistencies in the literature by relating volumetric analyses of white matter lesions (deep white matter lesions and periventricular lesions) to neuropsychological performance in a large clinical sample of older adults diagnosed with mild cognitive impairment., Methods: Seventy older adults with mild cognitive impairment were administered a comprehensive neuropsychological battery. White matter lesions identified on T2-weighted FLAIR images were quantified using a semi-automated volumetric approach (pixel thresholding)., Results: Results showed that, in contrast to performance on memory and naming tasks, total white matter lesions strongly predicted executive impairments, slowed processing speed, and visuospatial/construction difficulties. In addition, separate regression analyses demonstrated that results were primarily accounted for by deep white matter lesions (but not periventricular lesions), most likely due to frontal-subcortical circuitry disruption. Moreover, deep white matter lesions, but not periventricular lesions, significantly predicted overall poorer neuropsychological functioning after controlling for age, education, and level of depression., Conclusions: Taken together, findings demonstrate a differential influence of lesion type on cognitive impairment in mild cognitive impairment and implicate deep white matter lesions as being most detrimental in terms of neuropsychological functioning. Clinical, theoretical, and methodological implications of these results are discussed.

Background: Evidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear., Aims: To investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders., Method: In a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year., Results: Using logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (P<0.01)., Conclusions: White matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life.

Background/aims: The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) is a widely used rating instrument. The Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog) includes additional tests reflecting mental speed and executive functions. The objective of this study was to compare the results of the two scales among subjects with various degrees of white matter hyperintensities (WMHs)., Methods: In the multicentre, multinational Leukoaraiosis and Disability in the Elderly (LADIS) study, 616 non-disabled subjects between the ages of 65 and 84 were examined using MRI, the ADAS-cog and VADAS-cog. The WMH rating from the MRI divided the patients into groups of mild (n = 280), moderate (n = 187) and severe (n = 149) degrees of change., Results: Covariance analysis controlling for the effect of age and education revealed that the ADAS-cog differentiated only the mild and severe WMH groups, while the differences between all three groups were highly significant with the VADAS-cog., Conclusions: The VADAS-cog significantly differentiated between all the white matter groups. In comparison, the ADAS-cog differentiated only severe changes. Accordingly, the VADAS-cog may be a more sensitive endpoint in studies of patients with white matter load and vascular burden of the brain., ((c) 2007 S. Karger AG, Basel.)

Background: This study investigates the effect of leukoaraiosis on patients presenting with cognitive impairment after lacunar stroke., Methods: Fourty-six patients with cognitive impairment and newly discovered lacunar stroke detected by brain magnetic resonance imaging underwent neuropsychological testing., Results: Patients with both lacunar infarct and leukoaraiosis performed less well on cognitive measures, compared to those with lacunar infarcts alone. Additionally, leukoaraiosis severity inversely correlated with cognitive performance., Conclusions: In patients with lacunar stroke, presence of leukoaraiosis is associated with worse performance in multiple cognitive domains. These findings suggest lacunar infarcts plus leukoaraiosis is a common etiology for vascular dementia.