White matter microstructural alterations in migraine: a diffusion-weighted MRI study.

Migraine is a common and disabling neurological disease. The pathomechanism that underlies the disorder is not entirely understood, and reliable biomarkers are missing. In the current analysis we looked for microstructural alterations of the brain white matter in migraine patients by means of diffusion-weighted magnetic resonance imaging. The measurements were carried out with a novel approach based on fine-tuned nonlinear registration and nonparametric permutation test in an alignment-invariant tract representation (Tract-Based Spatial Statistics). We found reduced fractional anisotropy in the right frontal white matter cluster of migraine patients. In the same region we also found increased mean diffusivity and increased radial diffusivity. The probabilistic tractography showed connection of this cluster to other parts of the pain network (orbitofrontal cortex, insula, thalamus, dorsal midbrain). We speculate that these findings reflect maladaptive plastic changes or white matter disintegration.

Quality and quantity of diffuse and focal white matter disease and cognitive disability of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Using high-field magnetic resonance imaging (MRI), we investigated the relationships between white matter (WM) lesion volume (LV), normal-appearing WM (NAWM) normalized volume, WM-lesion and NAWM magnetization transfer ratios (MTRs), brain parenchyma fraction (BPF), and cognitive impairment (CI) in multiple sclerosis (MS). METHODS: Twenty-four patients and 24 healthy volunteers (age, sex, and years of education-matched) underwent a 3.0 Tesla (3T) scan and evaluation of depression, fatigue, and CI using the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. RESULTS: In this clinically relatively well-preserved cohort of patients (median score on the Expanded Disability Status Scale=1.5), CI was detected on Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II), and Controlled Oral Word Association Test. MT data were available in 19 pairs on whom correlation analyses were performed. Associations were seen between SDMT and normalized NAWM volume (P=.034, r=.502), CVLT-II long delay and normalized NAWM volume (P=.012, r=.563), WM-LV (P=.024, r=.514), and BPF (P=.002, r=.666). CONCLUSIONS: The use of 3T MRI in a sample of clinically stable MS patients shows the importance of WM disease in hampering processing speed and word retrieval.

Alzheimer's disease and endothelial dysfunction.

Recent studies suggest strong interactions between cerebrovascular and Alzheimer's disease (AD) pathology. These conditions share common risk factors and individuals having both frequently show greater cognitive impairment than those affected by only one disease. Many studies point to early vascular dysregulations in AD. The exchange between vascular and neural cells occurs through mechanisms not completely understood, involving interactions among endothelial, glial, neuronal and smooth muscle cells within the neurovascular unit. Studies suggest that the dysregulation of the unit is likely associated with hypertension and other systemic diseases. Associations between hypertension and cognitive decline are not established, but other variables associated with hypertension could create a causal link. Many studies have lacked a consistent, quantitative neuropsychological approach for assessing cognitive functions. This approach is reductive, as the need for a formal neuropsychological assessment has gained broad recognition, and the definition of dementia has gone through revision processes, which are in progress.

Clinical findings, functional abilities and caregiver distress in the early stage of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).

Few studies have compared neuropsychiatric disorders and functional abilities in the early stage of DLB and AD and their influence on caregiver distress. The aim of this study is to assess neuropsychiatric disorders, functional abilities and caregiver distress in DLB and in AD subjects. Sixteen subjects affected by probable DLB and 12 subjects affected by probable AD were enrolled. All subjects underwent a wide neuropsychological examination. Caregiver's distress was also assessed. Subjects affected by DLB performed better in long-term memory tests, whereas AD subjects performed better in attentive and executive function tests. The Neuropsychiatric Inventory (NPI) total score was significantly higher in DLB subjects than in AD subjects. Furthermore, DLB subjects scored worse than AD subjects in both Activities of Daily Living scale (ADL) and Instrumental Activities of Daily Living scale (IADL) scales. Overall caregiver distress was higher in DLB than in AD subjects. High distress was observed in DLB caregivers alone and was caused by delusion, hallucinations, anxiety and apathy. DLB subjects have a different neuropsychological profile, more psychiatric symptoms and more serious functional deficits than AD subjects in the early cognitive decline, furthermore DLB caregivers are more stressed than AD caregivers.

Heterogeneity in response to interferon beta in patients with multiple sclerosis: a 3-year monthly imaging study.

OBJECTIVES: To investigate the heterogeneity in magnetic resonance image (MRI) patterns of response to interferon beta across patients with multiple sclerosis or within an individual patient over time. DESIGN, SETTING, AND PATIENTS: Fifteen patients with relapsing-remitting multiple sclerosis underwent monthly MRIs and clinical examinations (6-month pretherapy phase and 36-month therapy phase) and bimonthly neutralizing antibody tests. On each MRI, the total number of contrast-enhancing lesions was noted. Therapy MRI responders were defined as those with a reduction of 60% or more in the total number of contrast-enhancing lesions during each semester of therapy. INTERVENTION: Subcutaneous administration of interferon beta-1b, 250 microg, every other day for 3 years. MAIN OUTCOME MEASURE: Reduction in the number of contrast-enhancing lesions. RESULTS: Eight patients (53.3%) were MRI responders and 7 (46.7%) were nonresponders. Of those 7, 3 (20.0%) had only an initial optimal reduction of the total number of contrast-enhancing lesions, 2 (13.3%) never reached an optimal response, and 2 (13.3%) had a delayed optimal response. No clear association between neutralizing antibody profile and MRI response was evident. CONCLUSIONS: Multiple MRI evaluations disclose that approximately only half of the patients treated with interferon beta achieve and maintain a full response to the drug over time, although an additional small number of individuals may still restore an optimal response to the drug after an initial failure.

Serum chemical elements and oxidative status in Alzheimer's disease, Parkinson disease and multiple sclerosis.

The role of some chemical elements in neurodegeneration was suggested by various authors. To obtain a profile of chemical elements and oxidative status in complex neurological diseases, an unbiased "omics" approach, i.e., quantification of 26 elements and oxidative stress parameters (serum oxidative status (SOS) and serum anti-oxidant capacity (SAC)), combined with multivariate statistical procedures (forward discriminant analysis, FDA) to analyse the vast amount of data, was applied to four groups of subjects (53 patients with Alzheimer's disease (AD), 71 with Parkinson disease (PD), 60 with multiple sclerosis (MS) and 124 healthy individuals). Descriptive statistics revealed numerous differences between each disease and healthy status. A concordant imbalance (reduction in Fe, Zn and SAC, and increase in SOS) was shared by AD, PD and MS. The FDA yielded three significant discriminant functions based on age, SOS, Ca, Fe, Si, Sn, V, Zn and Zr, and identified disease-specific profiles of element imbalances, thus showing the appropriateness of the "omics" approach. It may help assess the contribution of chemical elements and oxidative stress to disease causation and may provide complex predictors of disease evolution or treatment response.

Validity of the Italian telephone version of the mini-mental state examination in the elderly healthy population.

The biggest challenge regarding cognitive prospective evaluations in the elderly is the identification of subjects that go on to develop cognitive impairment. In this study, we compared the Italian telephone version of the MMSE (Itel-MMSE) with both the MMSE and a battery of neuropsychological tests in a group of 107 healthy elderly subjects. The aim of the study was to identify a subset of subjects who, despite having an overall score within the normal range, performed poorly in the cognitive neuropsychological evaluation. The Itel-MMSE score showed a good internal consistency as well as a significant correlation with the MMSE score, age and education. A score of < or = 21 on the Itel-MMSE was the score which reflected the highest degree of sensitivity in the neuropsychological tests. There was a statistically significant difference between subjects with an Itel-MMSE score of < or = 21 and those with a score of 22 in age, education, Attentional Matrices and Copying Drawings. Despite some potential limitations, our results strongly suggest that the Itel-MMSE may be used as a screening test to identify healthy elderly subjects whose cognitive performance is poor.

Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer's disease.

The haematic concentration of 26 metals and the oxidative damage in 60 patients (20 males and 40 females) affected by Alzheimer's disease and 44 healthy individuals (33 males and 11 females) were compared. In patients, the following significant (p < or = 0.05) discrepancies were found: i) increment of Ca, Cd, Hg, Mg, Si and Sn, and decrement of Al, Co, Fe and Zn in serum; ii) higher concentrations of Cu, Li, Mn, Sn and Zr and lower of Fe, Hg, Mo in blood; iii) overproduction of oxidant species (SOS) and decrease of the anti-oxidant capacity (SAC) (p < or = 0.001, for both). Variables that, joined, better discriminated between patients and controls resulted to be Si, SOS, SAC, Co, Ca, Al in serum (94% of cases correctly classified) and Cu, Zr, Mo and Fe in blood (90% of cases properly categorized).

Correlation between metal ions and clinical findings in subjects affected by Alzheimer's disease.

There is a growing interest to evaluate metals in biological fluids in Alzheimer's disease (AD). There are numerous studies on this theme, but just few papers analyzed the relationship between haematic metal concentrations and the clinical features of the disease. In this study, possible associations between clinical features of AD and the variations in serum and blood concentration of some metals, as well as the serum oxidative status and the antioxidant capacity have been investigated. Sixty subjects with AD were enrolled. Some elements correlated with gender, depression and duration of the disease. However, the most significant result was the relationship between blood Ca and Fe levels and the severity of cognitive impairment. We hypothesize that Ca and Fe might play an important role in the pathogenetic mechanisms of AD.