A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial.

Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p < 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p < 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.

Microemboli detection in patients with carotid artery stenting--a potential marker for future cognitive impairment?

AIMS: To monitor the long-term cognitive function evolution of patients undergoing carotid artery stenting (CAS), using detection of embolic signals (ES) as a potential marker of cognitive decline. METHODS: This is an ongoing prospective nonrandomized single-center study of patients undergoing carotid artery angioplasty and stenting using standard techniques. Neurologic status is evaluated by history, physical examination and the National Institutes of Health Stroke Scale. A complete Doppler-ultrasound investigation of the brain-supplying arteries has been performed in every patient. A 45minute cognitive battery designed to assess motor speed/coordination and executive function, psychomotor speed, language (naming), working memory/concentration, verbal fluency, and learning/memory is performed by a certified neuropsychologist in the first week after CAS and repeated a year after the procedure. Each patient undergoes bilateral ultrasonographic-Doppler monitoring of the middle cerebral artery (MCA) for microemboli detection. The patients are monitored during the first week after CAS and again a year after stenting. RESULTS: 32 patients were included. The mean baseline Mini-Mental State Examination (MMSE) score was 28.7 points. During the first ultrasonographic monitoring 28 patients (87.5%) had at least three times more ES detected on the stented side (a mean of 24ES/30minutes was detected in the stented side compared to a mean of 4ES/30min in the non-stented side). At the one-year follow-up 68% of the patients who have undergone CAS maintain a high number of ES detected in the territory of the stented carotid artery, finding that is well correlated with the cognitive decline in those patients, as assessed by the MMSE score. CONCLUSIONS: ES detection is a useful tool for predicting cognitive decline that can be used to monitor CAS patients and adjust preventive measures in order to avoid progression of vascular cognitive impairment. It is important that further studies comparing carotid endarterectomy and CAS monitor long-term cognitive function outcome.

Claudin expression profile separates Alzheimer's disease cases from normal aging and from vascular dementia cases.

We have reported earlier that tight-junction proteins are detectable by standard immunohistochemistry in the brain parenchyma, namely in the cell bodies of neurons, astrocytes, and oligodendrocytes. Here we show, by projection to latent structures - discriminate analysis (PLS-DA), that the immunohistochemical detection profile of tight junction proteins clearly distinguishes the AD cases from healthy aging controls and from the cases of dementia with a predominantly vascular pathology underlying the symptoms (vascular dementia, VaD; cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL; and cerebral amyloid angiopathy, CAA). Our findings might be valuable in the perspective of developing biomarkers for AD.