White matter hyperintensities and cognition across different Alzheimer's biomarker profiles.

BACKGROUND/OBJECTIVES: To examine the association between white matter hyperintensities (WMH) and cognitive domains such as memory and executive function (EF) across different clinical and biomarker categories of Alzheimer's disease (AD). DESIGN: Cross-sectional study. SETTING: Alzheimer's Disease Neuroimaging Initiative. PARTICIPANTS: A total of 216 cognitively normal (CN) participants and 407 participants with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) at baseline. MEASUREMENTS: Based on the 2018 research framework, participants were classified using AT(N) (amyloid-ß deposition [A], pathologic tau [T], and neurodegeneration [(N)]) biomarkers into one of three categories: biomarker negative [A - T- (N)-], amyloid negative but other biomarker positive [A - T ± (N)+ or A - T + (N)±] or amyloid positive [A + T ± (N)±]. Linear regression models were then used to examine the association between WMH and memory composite scores and EF composite scores. RESULTS: Higher WMH burden was associated with worse EF in both CN and MCI subgroups while a significant association between WMH and memory was only found in the MCI subgroup. Furthermore, WMH was associated with EF in the group with A - T ± (N)+ or A - T + (N)± biomarker category, but not for A - T - (N)- (normal biomarker) and A + T ± (N) ± (AD pathology). The association between higher WMH and worse memory was independent of amyloid levels in individuals with MCI with evidence of AD pathology. CONCLUSION: Vascular disease, as indexed by WMH, independent of AD pathology affects cognitive function in both CN and MCI subgroups. Future studies using the AT(N) research framework should consider white matter lesions as a key biomarker contributing to the clinical presentation of AD.

Leukoaraiosis Is Associated With a Decline in Language Abilities in Chronic Aphasia.

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 R2 = 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 R2 = 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 Predicts Short-term Cognitive But not Motor Recovery in Ischemic Stroke Patients During Rehabilitation.

BACKGROUND: Leukoaraiosis has been shown to impact functional outcomes after acute ischemic stroke. However, its association with domain specific recovery after ischemic stroke is uncertain. We sought to determine whether pre-existing leukoaraiosis is associated with short-term motor and cognitive recovery after stroke. METHODS: We retrospectively studied ischemic stroke patients admitted to acute inpatient rehabilitation (AIR) between January 2013 and September 2015. Patient baseline characteristics, infarct volume, prestroke modified Rankin Scale, stroke cause, rehabilitation length of stay, and Functional Independence Measure (FIM) scores were recorded. Leukoaraiosis severity was graded on brain magnetic resonance imaging using the Fazekas scale. Multiple linear regression was used to determine factors independently associated with the total, cognitive, and motor FIM scores at AIR discharge, respectively. RESULTS: Of 1600 ischemic stroke patients screened, 109 patients were included in the final analysis. After adjustment, the initial National Institute of Health Stroke Scale (ß -0.541, confidence interval [CI] -0.993 to -0.888; P = 0.020) and pre-existing leukoaraiosis severity (ß -1.448, CI -2.861 to -0.034; P = 0.045) independently predicted the total FIM score. Domain specific analysis showed that infarct volume (ß -0.012, CI -0.019 to -0.005; P = 0.002) and leukoaraiosis severity (ß -0.822, CI -1.223 to -0.410; P = 0.0001) independently predicted FIM cognitive scores at discharge from AIR. Leukoaraiosis did not predict FIM motor score (P = 0.17). CONCLUSIONS: Leukoaraiosis severity is an independent predictor of total and cognitive, but not motor FIM scores after AIR for acute ischemic stroke. This highlights that leukoaraiosis affects poststroke recovery in a domain specific fashion, information that may aid counseling of patients and families as well as tailor rehabilitative efforts.

Use of Multimodal Magnetic Resonance Imaging Techniques to Explore Cognitive Impairment in Leukoaraiosis.

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.

Functional magnetic resonance imaging with encoding task in patients with mild cognitive impairment and different severity of leukoaraiosis.

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.

Daily Living Activities and Cognition in Aged Patients: Effect of Acute Systemic Diseases and Stroke on Leukoaraiosis.

BACKGROUND: Acute Systemic Diseases (ASD) impact on extended leukoaraiosis (ExLA) have been seldom described. We study the deterioration in daily life activities (DLA) and cognition associated with ASD events compared with the well-described impacts of stroke in patients with leukoaraiosis (L-A). METHODS: Cross-sectional surveys of aged adults from the emergency room after an acute event of ASD or stroke, hospitalized or receiving home care, were followed for one year. From 268 initial patients 206 were included in the study, all with moderate to severe L-A (Fazekas 2 and 3). The Clinical Deterioration Rating (CDR) and the modified Rankin scale with structured interview were obtained one week previous to admission and after 3 and 12 months of evolution. Comparisons were conducted within and between groups with nonparametric techniques. RESULTS: We formed three groups of similar age, A: Inpatients with one Stroke, B: Inpatients with one ASD, and C: Outpatients with one ASD. A sudden deterioration in Rankin was evident in Group A, while in B and C impairment was progressive. Impairment in CDR was smooth in all groups while in Rankin it was always greater than in cognition (CDR). No differences were found in the associations between groups and risk factors, hypertension being the most frequent one. CONCLUSION: ASD in ExL-A causes a worsening of DLA and cognition similar to that observed in ExL-A with concomitant stroke indicating the need, in ageing patients, of differential diagnosis in order to achieve the best possible treatment.

Deep white matter hyperintensities, microstructural integrity and dual task walking in older people.

To examine neural, physiological and cognitive influences on gait speed under single and dual-task conditions. Sixty-two community-dwelling older people (aged 80.0 ± 4.2 years) participated in our study. Gait speed was assessed with a timed 20-meter walk under single and dual-task (reciting alternate letters of the alphabet) conditions. Participants also underwent tests to estimate physiological fall risk based on five measures of sensorimotor function, cognitive function across five domains, brain white matter (WM) hyperintensities and WM microstructural integrity by measuring fractional anisotropy (FA). Univariate linear regression analyses showed that global physiological and cognitive measures were associated with single (ß = 0.594 and ß=-0.297, respectively) and dual-task gait speed (ß = 0.306 and ß=-0.362, respectively). Deep WMHs were associated with dual-task gait speed only (ß = 0.257). Multivariate mediational analyses showed that global and executive cognition reduced the strength of the association between deep WMHs and dual-task gait speed by 27% (ß = 0.188) and 44% (ß = 0.145) respectively. There was a significant linear association between single-task gait speed and mean FA values of the genu (ß=-0.295) and splenium (ß=-0.326) of the corpus callosum, and between dual-task gait speed and mean FA values of Superior Cerebellar Peduncle (ß=-0.284), splenium of the Corpus Callosum (ß=-0.286) and Cingulum (ß=-0.351). Greater deep WMH volumes are associated with slower walking speed under dual-task conditions, and this relationship is mediated in part by global cognition and executive abilities specifically. Furthermore, both cerebellum and cingulum are related to dual-task walking due to their role in motor skill performance and attention, respectively.

Correlation between prefrontal-striatal pathway impairment and cognitive impairment in patients with leukoaraiosis.

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.

Leukoaraiosis is Associated with Worse Short-Term Functional and Cognitive Recovery after Minor Stroke.

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.

White Matter Changes and Cognitive Decline in a Ten-Year Follow-Up Period: A Pilot Study on a Single-Center Cohort from the Leukoaraiosis and Disability Study.

AIMS: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up. METHODS: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed. RESULTS: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (ß = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up. CONCLUSION: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years.

Impact of cerebral white matter changes on functionality in older adults: An overview of the LADIS Study results and future directions.

The evidence on the clinical significance of cerebral white matter changes (WMC) has mounted over the past few decades. WMC are recognized as one of the neuroimaging features of cerebral small vessel disease, and are associated with various disturbances and a poor prognosis. The Leukoaraiosis and Disability (LADIS) Study has contributed substantially to this body of knowledge. LADIS is a European multicenter collaboration aimed at assessing the role of WMC as an independent predictor of the transition to disability in initially non-disabled patients aged 65-84 years. Besides the demonstration that severe WMC cause a more than double risk of transition from an autonomous to a dependent status after 3 years of follow-up, the LADIS Study has also provided evidence on the role of WMC in relation to the decline of cognitive and motor performances, depressive symptoms associated with aging and cerebrovascular diseases, the presence of urinary disturbances, and various neurological abnormalities. The possible role of other lesions (lacunar infarcts, cerebral atrophy, corpus callosum morphology) and microstructural abnormalities (diffusion-weighted imaging changes in normal appearing brain tissue and in WMC) has also been investigated. In the present article, we review the main results of the LADIS Study and offer some considerations for future developments in the field, paying attention to the potential use of WMC progression as a surrogate marker in intervention trials in cerebral small vessel diseases. We also discuss some therapeutic perspectives regarding the beneficial impact of physical activity on the risk of vascular cognitive impairment in patients with WMC.

Leukoaraiosis with mild cognitive impairment.

As the ageing population continues to increase, the prevalence of age-related cognitive impairment has been on the rise. Mild cognitive impairment (MCI) is now widely recognised as the early stage of dementia. Mild cognitive impairment is closely associated with cerebral white matter lesions (WMLs), specifically in the case of leukoaraiosis (LA). A previous diffusion tensor imaging (DTI) has demonstrated that white matter changes might damage cognitive function in LA patients, and the cognitive function might decrease with the deterioration of LA. Through consulting and analysing documents, we found that both of them share similarities in risk factors, pathogenesis, pathological changes, and imaging manifestations. The main characteristics of LA patients with MCI (LACI) are the early and apparent manifestations of delayed memory, attention, impaired executive function, and close association with dementia. This analysis of LACI may contribute to an early diagnosis of LACI and provide possible treatment for LACI.

[Risk factors and predictive factors of cognitive deterioration in patients of vascular cognitive impairment no dementia with subcortical ischemic vascular disease].

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.

Neglect performance in acute stroke is related to severity of white matter hyperintensities.

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.

Executive dysfunction correlates with caudate nucleus atrophy in patients with white matter changes on MRI: a subset of LADIS.

White matter changes (WMC) are common magnetic resonance imaging (MRI) findings, particularly in the elderly. Recent studies such as the Leukoaraiosis and Disability Study (LADIS) have found that WMC relate to adverse outcomes including cognitive impairment, depression, disability, unsteadiness and falls in cross-sectional and follow-up studies. Frontostriatal (or frontosubcortical) brain circuits may serve many of these functions, with the caudate nuclei playing a role in convergence of cognitive functions. This study aimed to determine whether reduced caudate volume relates to cognitive functions (executive functions, memory functions and speed of processing) and WMC. We determined caudate nuclei volumes, through manual tracing, on a subgroup of the LADIS study (n=66) from four centres with baseline and 3-year follow-up MRI scans. Regression analysis was used to assess relationships between caudate volume, cognitive function and WMC. Severity of WMC did not relate to caudate volume. Smaller caudate volumes were significantly associated with poorer executive functioning at baseline and at 3 years, but were not associated with scores of memory or speed of processing. Thus, in patients with WMC, a surrogate of small vessel disease, caudate atrophy relates to the dysexecutive syndrome, supporting the role of caudate as an important part of the frontostriatal circuit.

[Influence of leukoaraiosis on the cognition of patients with Parkinson disease].

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, ß = 0.600), DHs (P = 0.001, ß = -0.678) and HY (P = 0.035, ß = -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.

Leukoaraiosis, a common brain magnetic resonance imaging finding, as a predictor of traffic crashes.

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.

Suitability of the Montreal cognitive assessment versus the mini-mental state examination in detecting vascular cognitive impairment.

The Mini-Mental State Examination (MMSE) has been criticized as being an insufficient screening test for patients with vascular cognitive impairment because of its insensitivity to visuospatial and executive functional deficits. The Montreal Cognitive Assessment (MoCA) was designed to be more sensitive to such deficits, and thus may be a superior screening instrument for vascular cognitive impairment. Twelve patients with extensive leukoaraiosis detected on magnetic resonance imaging (average age, 76.0 ± 8.7 years) underwent neurologic and cognitive testing, including MMSE and the Japanese version of the MoCA (MoCA-J). Accepted cutoff scores of <27 for the MMSE and <26 for the MoCA-J were taken to indicate cognitive impairment. Z-scores were calculated to evaluate the discriminating ability of individual MMSE and MoCA-J subtest scores. Although there was a strong correlation between the total MMSE and total MoCA-J scores (r = 0.90; P < .0001), MMSE scores were skewed toward the higher end of the range (range, 18-30; median, 28), whereas MoCA-J scores were normally distributed (range, 9-28; median, 21). Of the 7 patients with an unimpaired MMSE score, 6 (86%) had an impaired MoCA-J score. Z-scores were >5 for 4 MMSE subtests (orientation, registration, naming, and language) but for only 1 MoCA-J subtest (naming). The MoCA-J better discriminated cognitive status in subjects with extensive leukoaraiosis. Our findings suggest that the MoCA-J is more sensitive than the MMSE in screening for cognitive impairment in patients with subcortical vascular cognitive impairment.

Association of physical activity with the visuospatial/executive functions of the montreal cognitive assessment in patients with vascular cognitive impairment.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is more suitable than the Mini-Mental State Examination (MMSE) for the detection of vascular cognitive impairment. In this study, we performed a correlation analysis of MoCA/MMSE scores with daily physical activity in patients with subcortical ischemic white matter changes. METHODS: Ten patients (average 75.9 ± 9.1 years old) with extensive leukoaraiosis detected on magnetic resonance imaging underwent cognitive testing, including the MMSE and the Japanese version of the MoCA (MoCA-J). Physical activity was monitored with the Kenz Lifecorder EX device (Suzuken, Nagoya, Japan) to assess daily physical activity in terms of caloric expenditure, motor activity, number of steps, and walking distance for 6 months. Correlations of individual physical activity with total and subscale scores of MMSE/MoCA-J or 6-month interval change of MoCA-J scores were assessed. RESULTS: The total or subscale scores of the MMSE did not correlate with any parameters of physical activity. However, the mean number of steps and walking distance significantly correlated with the total MoCA-J scores (r = .67 and .64, respectively) and its visuospatial/executive subscores (r = .66 and .66, respectively). The mean interval change of MoCA-J was + .6; those who improved number of steps (n = 4; 80.5 ± 3.0 years of age) had significantly preserved MoCA-J scores compared to those who did not (n = 6; 73.0 ± 11.6 years of age; +2.0 versus - .3; P = .016). CONCLUSIONS: These results suggest that MoCA is useful to detect a biologically determined specific relationship between physical activity and executive function. In addition, physical exercise, such as walking, may help enhance cognitive function in patients with vascular cognitive impairment of subcortical origin.

Low cerebrospinal fluid sulfatide predicts progression of white matter lesions: The LADIS study.

BACKGROUND/AIMS: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. METHODS: CSF from elderly individuals with WML was analyzed for amyloid markers, total τ, hyperphosphorylated τ, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). RESULTS: 37 subjects (age 73.6 ± 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0-2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). CONCLUSION: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer's disease.