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Background . A fraction of stroke survivors with chronic aphasia experience declines in language abilities over time, but the reason for this remains unclear. Objective . To evaluate the effect of leukoaraiosis on baseline aphasia severity and long-term changes in aphasia severity. This study directly compares the predictive capacity of leukoaraiosis severity to that of lesion damage, a factor known to account for a substantial proportion of variance in the degree of language impairment and recovery. Methods . Using a longitudinal database of behavioral and neuroimaging data from 35 individuals in the chronic stage of recovery after a single-event left-hemisphere stroke (9 females, mean stroke age = 55.8 ± 9.1 years, mean months poststroke at initial evaluation = 36.3 ± 40.8), we examined 2 lines of inquiry: (1) to what extent does leukoaraiosis severity at initial evaluation predict aphasia severity and (2) to what extent does leukoaraiosis severity at initial evaluation predict longitudinal change in aphasia severity. Participants underwent high-resolution magnetic resonance imaging for the purpose of lesion volume analysis and leukoaraiosis severity rating. Biographical information was also considered. Results . Lesion volume and time poststroke at initial assessment best predicted initial aphasia severity (adjusted R 2 = 0.37). Leukoaraiosis severity and initial aphasia severity significantly predicted decline in language abilities at follow-up, accounting for approximately one-third of the variance (adjusted R 2 = 0.33). More severe leukoaraiosis was associated with a 4.3 odds increase of decline. Conclusions . Leukoaraiosis is a significant risk factor for declining language abilities in aphasia and should be considered for better identification of individuals at risk for long-term decline, which can guide clinical decision making.

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.

Our study aimed to investigate the changes of white matter microstructure of cortico-subcortical pathways using diffusion tensor imaging (DTI), and to explore the relationship between abnormal parameters of DTI and cognitive function underlying in patients with leukoaraiosis (LA).A total of 42 patients with LA and 42 age- and sex-matched healthy controls were recruited from Beijing Chaoyang Hospital, Capital Medical University between January 2012 and December 2012. All the subjects underwent scans of conventional magnetic resonance imaging and DTI, and a comprehensive neuropsychological battery was utilized. The regions of interest (ROIs) were located at the white matter of centrum semiovale, anterior and posterior periventricular white matter, basal ganglia, corpus callosum. The averaged values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal appearing white matter (NAWM). A linear regression analysis was performed to assess the association between diffusion parameters and decline in cognitive domains.Patients with LA were associated with comprehensive cognitive function deficits. We found that significantly decreased FA and increased MD in WMLs at the 5 ROIs than that of NAWM and controls (P < .05). The values of FA in NAWM were significantly lower and MD in NAWM were significantly higher at centrum semiovale and posterior periventricular white matter than that of controls (P < .05). The values of FA in WMLs at anterior periventricular white matter were positively related to the performances of cognition in patients with LA (P < .05). The values of FA in NAWM located at anterior periventricular white matter were positively related to the score of Digit-symbol test (r = 0.446, P = .002). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.418, P = .03).In our study, patients with LA exhibited significant cognitive impairment especially in the domains of executive function. The technique of DTI revealed that the reduced FA and increased MD at the corresponding regions of cortico-subcortical pathways in patients with LA. DTI may be of great help for an early pathology of white matter microstructure underlying in patients with LA.

Whether leukoaraiosis burden retards short-term recovery after minor stroke is unclear. We investigated the association between leukoaraiosis and early recovery of neurological function after a first minor ischemic stroke in 217 acute stroke patients (National Institutes of Health Stroke Scale (NIHSS) score ≤5). Leukoaraiosis severity was graded according to the Fazekas scale and categorized into none to mild (0-2; n = 143) or severe (3-6; n = 74) groups. NIHSS and Minimum Mental State Examination (MMSE) were assessed at baseline and at 30 days. Univariate analysis revealed that the severe leukoaraiosis group was older in age (P < 0.001) and had fewer low MMSE patients than non-mild group at baseline (39.1% vs 55.9%, P = 0.003). However, the MMSE improved in none to mild group but not in the severe group at 30-day (15.4% vs 36.5%, P < 0.001). At 30-day, the severe leukoaraiosis group had higher NIHSS scores than the none-mild group (P = 0.04). Multiple linear regression analyses demonstrated that leukoaraiosis severity and admission NIHSS were independently associated with the NIHSS score on day 30 (P = 0.034, 95% CI 0.004-0.091 and P = 0.001, 95% CI 0.011-0.04). Binary regression analyses showed that leukoaraiosis severity and admission MMSE were significantly associated with MMSE (dichotomized) at 30-day (OR 2.1, P < 0.01, 95% CI 1.7-2.6 and OR 5.1, P < 0.01, 95% CI 2.1-12.8). Leukoaraiosis burden is an independent predictor of worse short-term functional and cognitive recovery after a minor ischemic stroke.

Objective: To explore the independent risk factors and predictive factors of cognitive deterioration in patients of vascular cognitive impairment no dementia with subcortical ischemic vascular disease (VCIND-SIVD)., Methods: The clinical and neuropsychological characteristics of 96 VCIND-SIVD patients were collected and their cognitive states re-assessed after one year. The distribution of continuous and categorical variables was examined with univariate analysis. And Logistic regression in multivariate modeling was employed to identify the risk and predictive factors of cognitive deterioration., Results: After 1-year follow-up, 8 patients dropped out, 2 died and the remainder remained. There were 48 males and 38 females with an average age of 64.3 ± 5.4 years. Among them, 17 (19.8%) deteriorated into dementia, 24 (27.9%) upgraded to normal cognition and 45 (52.3%) maintained their cognitive status. They were divided into dementia group (cognition deteriorating into dementia) and control group (elevated/sustained cognition). After univariate analysis of general information and vascular risk factors, Logistic regression demonstrated that education level (P < 0.05, OR = 0.7) was a preventive factor of dementia while age (P < 0.05, OR = 1.2), hypertension (P < 0.05, OR = 5.6) and high homocysteine (P < 0.05, OR = 4.2) were independent risk factors of dementia. After univariate analysis of neuropsychological scores, Logistic regression demonstrated that visual reproduction-immediate recall (P < 0.05, OR = 3.4), digit span forward (P < 0.05, OR = 1.2), clock drawing test (P < 0.05, OR = 6.8) and completion time of London tower (P < 0.05, OR = 5.4) were predictive factors of dementia., Conclusion: VCIND-SIVD patients with low score of visual reproduction-immediate recall, digit span forward, clock drawing test and completion time of London tower should receive vigorous controls of hypertension and high homocysteine.

Objective: To explore the role of leukoaraiosis (LA) on the cognitive function in patients with Parkinson disease (PD)., Methods: The cohort for this study included 63 patients with PD, whom were divided into 3 groups according to cognitive status:with intact cognition (PD-IC, n = 23), with mild cognitive impairment (PD-MCI, n = 23) and with dementia (PDD, n = 17). All the patients were recruited from the Department of Neurology, First Affiliated Hospital, Anhui Medical University between September 2011 and July 2012. The cognitive functions were evaluated by mini-metal state examination (MMSE), the Cambridge cognitive examination-Chinese version (CAMCOG-C), clinical dementia rating (CDR), clock drawing task (CDT) and verbal fluency test, etc. Depression symptoms were assessed by the geriatric depression scale (GDS) while motor symptoms by the Unified Parkinson's Disease Rating Scale-motor (UPDRS-motor) and the Hoehn and Yahr scale (HY). All the patients underwent magnetic resonance imaging (MRI) with a 3.0-T system. LA was rated using the semiquantitative visual rating system proposed by scheltens et al., Results: Both the PD-IC (2.43 ± 2.79) and PD-MCI (4.48 ± 4.33) groups showed significantly lower deep hyperintensities (DHs) scores than the PDD group (7.88 ± 6.69, P = 0.004 and 0.040, respectively), especially in frontal (1.09 ± 1.31; 1.83 ± 1.90; 3.24 ± 2.64, P < 0.05) and parietal areas (0.09 ± 0.29; 0.65 ± 1.03; 1.53 ± 2.32, P < 0.05). There were no significant differences in periventricular (1.57 ± 1.75; 2.52 ± 2.37; 3.24 ± 2.64, P > 0.05), basal ganglia (0.09 ± 0.42; 0.30 ± 0.77; 0.53 ± 1.33, P > 0.05) and infratentorial white matter hyperintensities scores (--; 0.13 ± 0.63; 0.18 ± 0.73, P > 0.05) among three groups. The DHs showed a significant correlation with age (P = 0.003), MMSE (P = 0.009), verbal fluency test (P = 0.009), orientation (P = 0.047) and executive function (P = 0.027) in CAMCOG-C. The multiple regression analysis showed that the MMSE scores were associated significantly with education (P < 0.001, β = 0.600), DHs (P = 0.001, β = -0.678) and HY (P = 0.035, β = -0.480). DHs were the most significantly associated with MMSE scores., Conclusion: There was a significant correlation between DHs and multiple domain cognitive impairment in PD, especially in executive function. DHs, which were the most significantly variable associated with MMSE scores, may contribute to cognitive impairment in PD.

Background: There are no reported studies on the relationship between traffic crashes and brain tissue changes in healthy drivers. The relationship between traffic crashes and leukoaraiosis, a common magnetic resonance imaging finding, was investigated in this study., Methods: A total of 3,930 automobile drivers (2,037 men and 1,893 women; age, 21-87 years) who underwent brain magnetic resonance imaging as part of total health check-ups and answered a road traffic questionnaire were examined to determine whether asymptomatic leukoaraiosis was associated with various types of traffic crashes. Multiple logistic regression analysis was performed to elucidate the relationship between leukoaraiosis and various types of traffic crashes., Results: Subcortical leukoaraiosis was diagnosed in 28.52% of all subjects, whereas periventricular leukoaraiosis was diagnosed in 9.57% of all subjects. Adjusted odds ratios for involvement in all types of traffic crashes were not significant for subjects with periventricular leukoaraiosis; however, they were significant for subjects with multiple and large multiple subcortical leukoaraiosis. Adjusted odds ratios for involvement in crashes at crossroads were 1.09 (95% confidence interval [CI], 0.60-2.00) for subjects with single subcortical leukoaraiosis, 3.35 (95% CI, 2.36-4.77) for subjects with multiple subcortical leukoaraiosis, and 2.45 (95% CI, 2.36-4.98) for subjects with large multiple subcortical leukoaraiosis. Periventricular leukoaraiosis was not significantly associated with crossroad crashes. Involvement in crashes of any type, parking lot crashes, and rear-end collisions showed no significant association with either subcortical or periventricular leukoaraiosis., Conclusions: Multiple subcortical leukoaraiosis, but not periventricular leukoaraiosis, is significantly associated with traffic crashes, in particular, crossroad crashes. This association is independent of sex, age, and driving exposure. To our knowledge, this is the first evidence describing the relationship between brain tissue changes and traffic crashes.

Objective: To explore the pathological changes in patients with leukoaraiosis (LA) by magnetic resonance spectroscopy (MRS) and examine its relationship with cognitive function., Methods: Twenty-three LA patients and 23 age and gender-matched healthy subjects were recruited from the Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University between August 2010 and November 2010. All participants underwent the neuropsychological tests. Multi-voxel chemical shift imaging was performed and the regions of interest were positioned in bilateral frontal white matter. The relative metabolite ratios, involving N-acetyl aspartate/choline ratio (NAA/Cho), N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr), were estimated. The correlation of the MRS data and the performance of cognitive function was analyzed., Results: The LA patients were associated with a worse performance of mini mental state examination (MMSE) versus the healthy controls (24 ± 3 vs 28 ± 1, P < 0.05). Univariate analysis of the MRS data revealed the ratios of NAA/Cho and NAA/Cr significantly decreased in bilateral frontal white matter lesions in the LA group versus the control group (1.72 ± 0.20 vs 1.96 ± 0.36, 1.67 ± 0.17 vs 1.85 ± 0.21, P < 0.05). The values of NAA/Cr and NAA/Cho in normal appearing white matter increased versus the LA group (1.83 ± 0.24 vs 1.72 ± 0.20, 1.78 ± 0.28 vs 1.67 ± 0.17) and decreased versus the control group (1.83 ± 0.24 vs 1.96 ± 0.36, 1.78 ± 0.28 vs 1.85 ± 0.21). But no significant differences were found (P > 0.05). The ratio of Cho/Cr did not differ among 3 groups (P > 0.05). The pathological change of NAA/Cr in white matter lesion in LA patients was markedly correlated with the performance of MMSE (r = 0.47, P < 0.05)., Conclusion: NAA may be a marker of axonal loss/dysfunction in LA patients. And the changes of NAA/Cr have a positive correlation with cognitive impairment.

Objective: To explore the characteristics of cognitive impairment in patients with leukoaraiosis (LA)., Methods: Forty-six LA patients and 38 age and gender-matched healthy subjects were recruited from the Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University between September 2010 and March 2011. All participants underwent the neuropsychological tests recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards (NINDS/CSN). The were divided into 3 different groups (mild, moderate and severe) according to the Fazekas scale. The differences of neuropsychological performances were compared among 3 groups., Results: The LA patients were associated with comprehensive cognitive function deficits, including MMSE (24.4 ± 3.2 vs 28.3 ± 1.2), MoCA (20.4 ± 3.0 vs 26.2 ± 0.8), digital span forward (5.7 ± 0.9 vs 6.8 ± 1.0), digital span backward (3.5 ± 0.7 vs 4.1 ± 0.7), Stroop-B (69 ± 13 vs 43 ± 5), Stroop-C (141 ± 42 vs 65 ± 10), trail making test-A (73 ± 15 vs 31 ± 7), trail making test-B (126 ± 18 vs 82 ± 6) and digit symbol test (25 ± 6 vs 37 ± 5, P < 0.05). However, there was no difference in the performance of verbal fluency (12.7 ± 2.5 vs 13.4 ± 2.5, P > 0.05). Correlation analysis showed that the severity of LA had a negative correlation with the performance of MoCA (r = -0.601, P = 0.002)., Conclusions: The LA patients are closely correlated with cognitive impairments of attention, memory, executive function and information processing speed. It may be attributed to the frontal-subcortical circuitry dysfunction.

Background and Purpose: The mechanisms by which leukoariosis impacts on clinical and cognitive functions are not yet fully understood. We hypothesized that ultrastructural abnormalities of the normal-appearing brain tissue (NABT) assessed by diffusion-weighted imaging played a major and independent role., Methods: In addition to a comprehensive clinical, neuropsychologic, and imaging work-up, diffusion-weighted imaging was performed in 340 participants of the multicenter leukoariosis and disability study examining the impact of white matter hyperintensities (WMH) on 65- to 85-year old individuals without previous disability. WMH severity was rated according to the Fazekas score. Multivariate regression analysis served to assess correlations of histogram metrics of the apparent diffusion coefficient (ADC) of whole-brain tissue, NABT, and of the mean ADC of WMH with cognitive functions., Results: Increasing WMH scores were associated with a higher frequency of hypertension, a greater WMH volume, more brain atrophy, worse overall cognitive performance, and changes in ADC. We found strong associations between the peak height of the ADC histogram of whole-brain tissue and NABT with memory performance, executive dysfunction, and speed, which remained after adjustment for WMH lesion volume and brain atrophy and were consistent among centers. No such association was seen with the mean ADC of WMH., Conclusions: Ultrastructural abnormalities of NABT increase with WMH severity and have a strong and independent effect on cognitive functions, whereas diffusion-weighted imaging metrics within WMH have no direct impact. This should be considered when defining outcome measures for trials that attempt to ameliorate the consequences of WMH progression.

Objective: To apply diffusion tensor imaging (DTI) for investigating the correlation between leukoaraiosis (LA) lesion's fraction anisotropy (FA) as well as average diffusion coefficient (DCavg) and LA severity, so as to explore DTI changes in microstructure of white marrow with normal ordinary MRI and its correlation with cognitive function., Methods: Sixty LA patients and 30 healthy elderly people accepted DTI examination to detect the value of DCavg and FA of LA lesion and normal white marrow. The Mini-Mental State Examination (MMSE) was used for assessing cognitive function., Results: LA severity (0 grade to 3 grade) was positively associated with DCavg, i.e. the more severe was LA, the higher DCavg was (0.66 +/- 0.05 to 1.09 +/- 0.06, P < 0.05); and it was negatively associated with FA, i.e. the more severe was LA, the lower FA was (0.42 +/- 0.04 to 0.26 +/- 0.03, P < 0.05). Neuropsychology tests (Mini-Mental State Examination, MMSE) had a significant relationship with DCavg and FA of normal appearing white matter (NAWM) in LA patients (P < 0.05), especially in anterior horn (Pearson Correlation Coefficient 0.422, P < 0.05) and in centrum semiovale (Pearson Correlation Coefficient -0.495, P < 0.01)., Conclusions: In DTI examination, DCavg and FA of LA displays characteristic changes. Therefore, DTI can detect the macrostructaral changes of white marrow with normal MRI and these changes are related to cognitive function.

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.

Cerebral small-vessel disease is common in older people and may contribute to the development of dementia. The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study. Participants were 60-90 years of age and free from dementia at baseline in 1995-1996. White matter lesions (WML), cerebral infarcts and generalized brain atrophy were assessed on the baseline MRI. We performed neuropsychological testing at baseline and repeatedly in 1999-2000 and in 2001-2003. We used random-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function, information processing speed, executive function and memory. There were a total of 2266 assessments for the 832 participants in the study, with an average time from the initial to last assessment of 5.2 years. Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in cognitive function. These structural brain changes were specifically associated with decline in information processing speed and executive function. The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood. After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant. This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline. Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function.