Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline.

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

White matter microstructural damage in small vessel disease is associated with Montreal cognitive assessment but not with mini mental state examination performances: vascular mild cognitive impairment Tuscany study.

BACKGROUND AND PURPOSE: Montreal Cognitive Assessment (MoCA) has been proposed as a screening tool in vascular cognitive impairment. Diffusion tensor imaging is sensitive to white matter microstructural damage. We investigated if diffusion tensor imaging-derived indices are more strongly associated with performances on MoCA or on the widely used mini mental state examination in patients with mild cognitive impairment and small vessel disease. METHODS: Mild cognitive impairment patients with moderate/severe degrees of white matter hyperintensities on MRI were enrolled. Lacunar infarcts, cortical atrophy, medial temporal lobe atrophy and median values of mean diffusivity and fractional anisotropy of the cerebral white matter were studied and correlated with cognitive tests performances. RESULTS: Seventy-six patients (mean age 75.1±6.8 years, mean years of education 8.0±4.3) were assessed. In univariate analyses, a significant association of both MoCA and mini mental state examination scores with age, education, cortical atrophy, and medial temporal lobe atrophy was found, whereas mean diffusivity and fractional anisotropy were associated with MoCA. In partial correlation analyses, adjusting for all demographic and neuroimaging variables, both mean diffusivity and fractional anisotropy were associated only with MoCA (mean diffusivity: r= -0.275, P=0.023; fractional anisotropy: r=0.246, P=0.043). CONCLUSIONS: In patients with mild cognitive impairment and small vessel disease, diffusion tensor imaging-measured white matter microstructural damage is more related to MoCA than mini mental state examination performances. MoCA is suited for the cognitive screening of patients with small vessel disease.

Confirmatory factor analysis of the Neuropsychological Assessment Battery of the LADIS study: a longitudinal analysis.

Age-related white matter changes have been associated with cognitive functioning, even though their role is not fully understood. This work aimed to test a 3-factor model of the neuropsychological assessment battery and evaluate how the model fit the data longitudinally. Confirmatory factor analysis (CFA) was used to investigate the dimensions of a structured set of neuropsychological tests administered to a multicenter, international sample of independent older adults (LADIS study). Six hundred and thirty-eight older adults completed baseline neuropsychological, clinical, functional and motor assessments, which were repeated each year for a 3-year follow-up. CFA provided support for a 3-factor model. These factors involve the dimensions of executive functions, memory functions, and speed and motor control abilities. Performance decreased in most neuropsychological measures. Results showed that executive functioning, memory and speed of motor abilities are valid latent variables of neuropsychological performance among older adults, and that this structure is relatively consistent longitudinally, even though performance decreases with time.

Factors predicting the Montreal cognitive assessment (MoCA) applicability and performances in a stroke unit.

The evaluation of cognitive status is not routine in the acute stroke setting. We aimed to investigate feasibility, applicability, and performances of the Montreal cognitive assessment (MoCA) in acute stroke patients. Consecutive stroke patients (ischemic or hemorrhagic) admitted to one stroke unit were evaluated 5-9 days after stroke with MoCA (score range: 0-30; higher scores indicate better cognitive performance). Pre-morbid functional and cognitive status was assessed by a structured interview to caregivers. Neuroimaging data regarding index stroke and pre-existing lesions were collected. From December 2009 to December 2010, out of 207 patients with stroke, 137 (66%) were enrolled [mean age 69.2 ± 14.8 years; males 62%; mean National Institute of Health and Stroke Scale (NIHSS) score 5.9 ± 7.9]. The most common reason for non-enrolment was unfitting the time window inclusion criteria. MoCA was entirely applicable to 113/137 (82.5%) patients and the mean score was 17.8 ± 7.1. Multivariate analyses showed that non-applicability was associated with higher NIHSS scores [OR (95% CI) = 1.4 (1.2-1.7) for each point], left sided lesions [OR (95% CI) = 18.8 (2.3-155.2)], and worse pre-morbid functional status [OR (95% CI) = 0.7 (0.6-0.9) for each point of the instrumental activity of daily living scale]. Factors influencing MoCA performance were low education (ß = 0.264, p < 0.01), higher NIHSS scores (ß = -0.277, p < 0.01) and worse pre-morbid functional status (ß = 0.504, p < 0.001). MoCA administration is feasible in acute patients with mild-to-moderate stroke, with lesion location, stroke severity, and pre-morbid functional status as major determinants of its applicability and performance. MoCA seems to reveal some degree of cognitive deficit even in patients with mild stroke.

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.

Comparison of the Alzheimer's Disease Assessment Scale Cognitive Subscale and the Vascular Dementia Assessment Scale in differentiating elderly individuals with different degrees of white matter changes. The LADIS Study.

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.

Cerebrovascular disease in Italy and Europe: it is necessary to prevent a 'pandemia'.

In Italy and Europe, strokes are the third most common cause of death and resulting invalidity. In the ever-increasing 80-years-old-and-over people, strokes become more serious due to the clinical presentation during the acute phase and the ten-times higher mortality, but also in relation to the twice as high resulting disability as for younger subjects. However, stroke prevention is possible both through correct behavioural habits and pharmacological means. Besides the well-known preventive effects of an adequate anti-hypertensive, anti-diabetic and/or anti-aggregant/anti-coagulant therapy, there are increasing evidences of the effectiveness of the anti-hypercholesterolemic therapy in stroke prevention. Moreover, a great part of the risk factors for the cerebrovascular disease coincides with those for cardiovascular disease, for which the correction of the former automatically involves a reduction in incidence of both pathologies. In this context, a statin's rational use can therefore represent an important tool for the combined prevention of the two pathologies. Finally, different hypotheses link the origin of Alzheimer's disease to that of progressive cerebrovascular dementia caused by cerebral microcirculation damage. It is plausible that the application of a suitable early prevention of the cerebrovascular pathology could bring to a more late slatentisation and less serious demonstrations of Alzheimer's disease, when this is destined to develop.