Barbara Corrà

Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer's disease.

Upregulation of a number of chemokines, including monocyte chemotactic protein-1 (MCP-1), is associated with Alzheimers disease (AD) pathological changes. Emerging evidence suggests that inflammatory events precede the clinical development of AD, as cytokine disregulation has been observed also in patients with mild cognitive impairment (MCI). MCP-1 levels were evaluated in serum samples from 48 subjects with MCI, 94 AD patients and 24 age-matched controls. Significantly increased MCP-1 levels were found in MCI and mild AD, but not in severe AD patients as compared with controls. mRNA levels in peripheral blood mononuclear cells (PBMC), evaluated by quantitative RT-PCR analysis, paralleled serum MCP-1 levels. Moreover, a progressive MCP-1 decrease was observed over a 1-year follow up in a subgroup of MCI subjects converted to AD. MCP-1 upregulation is likely to be a very early event in AD pathogenesis, by far preceding the clinical onset of the disease. Nevertheless, as MCP-1 is likely to play a role in several pathologies with an inflammatory component, a possible usefulness as an early AD biomarker would be possible only in combination with other molecules.

Validating the neuro vr-based virtual version of the multiple errands test: Preliminary results

The purpose of this study was to establish ecological validity and initial construct validity of the virtual reality version of the Multiple Errands Test based on NeuroVR software as an assessment tool for executive functions. In particular, the Multiple Errands Test is an assessment of executive functions in daily life which consists of tasks that abide by certain rules and is performed in a shopping mall-like setting where there are items to be bought and information to be obtained. The study population included three groups: post-stroke participants (n = 9), healthy young participants (n = 10), and healthy older participants (n = 10). The general purpose of the study was investigated through the following specific objectives: (1) to examine the relationships between the performance of three groups of participants in the Virtual Multiple Errands Test (VMET) and in the traditional neuropsychological tests employed to assess executive functions; and (2) to compare the performance of post-stroke participants to those of healthy young and older controls in the Virtual Multiple Errands Test and in the traditional neuropsychological tests employed to assess executive functions. Correlations between Virtual Multiple Errands Test variables and some traditional executive functions measures provide preliminary support for the ecological and construct validity of the VMET; further performance obtained at the Virtual Multiple Errands Test provided a distinction between the clinical and healthy population, and between the two age control groups. These results suggest a possible future application of such an ecological approach for cognitive assessment and rehabilitation of stroke patients and elderly population with age-related cognitive decline.

Implementation of the Multiple Errands Test in a NeuroVR supermarket: A possible approach

Our goal was to develop a tool for the assessment of executive functions by customizing a virtual reality (VR) version of the Multiple Errands Test (MET) [Shallice & Burgess, 1991; Fortin et al., 2003]. The MET is an assessment of executive functions in daily life which consists of tasks that abide by certain rules. It is performed in an actual shopping mall-like setting where there are items to be bought and information to be obtained. The specific goal of this study was to conduct a pilot study using the virtual version of MET (VMET) with both control subjects and patients with cognitive impairment derived from stroke.

Candidate gene analysis of IP-10 gene in patients with Alzheimer's disease

Interferon-gamma-inducible Protein-10 (IP-10) is supposed to play a role in Alzheimers disease (AD) development, as demonstrated by increased levels in cerebrospinal fluid from patients with AD. A mutation scanning of IP-10 exonic region was carried out in 10 patients with AD and 10 age-matched controls, demonstrating the presence of two previously reported single nucleotide polymorphisms (SNPs) in exon 4 (G-->C and T-->C) as well as a novel SNP in exon 2 (C-->T). Exon 4 G-->C and T-->C allelic variants were next evaluated in a population of 279 AD patients and 251 controls, in order to determine whether their presence could influence the susceptibility towards the development of the disease. These two SNPs were in complete linkage disequilibrium. No differences in haplotype frequencies were found in AD patients as compared with controls, even stratifying according to the presence of Apolipoprotein E varepsilon4 allele, gender or age at onset. A new protocol was developed to easily determine the C-->T SNP in exon 2. A preliminary analysis revealed a very low frequency of this allelic variant (1%). Therefore, the complete association study was not carried out because the size of our population was not sufficient to draw reliable conclusions. According to these results, IP-10 does not seem to be a risk factor for AD. However, a novel rare polymorphism has been identified, which could exert a role in AD susceptibility. Thus, further studies on larger populations are needed before confidently excluding IP-10 as a susceptibility gene for AD.

Validation of a Neuro Virtual Reality-based version of the Multiple Errands Test for the assessment of executive functions.

The purpose of this study was to establish ecological validity and initial construct validity of the Virtual Reality (VR) version of the Multiple Errands Test (MET) (Shallice & Burgess, 1991; Fortin et al., 2003) based on the NeuroVR software as an assessment tool for executive functions. In particular, the MET is an assessment of executive functions in daily life, which consists of tasks that abide by certain rules and is performed in a shopping mall-like setting where items need to be bought and information needs to be obtained. The study population included three groups: post-stroke participants (n = 5), healthy, young participants (n = 5), and healthy, older participants (n = 5). Specific objectives were (1) to examine the relationships between the performance of three groups of participants in the Virtual Multiple Errands Test (VMET) and at the traditional neuropsychological tests employed to assess executive functions and (2) to compare the performance of post-stroke participants to those of healthy, young controls and older controls in the VMET and at the traditional neuropsychological tests employed to assess executive functions.

A NeuroVR based tool for cognitive assessment and rehabilitation of post-stroke patients: two case studies.

Neuropsychological disorders are common in stroke patients, ranging from an isolated impairment to impairment in multiple cognitive functions. The cognitive domains affected are in particular executive functions. These comprise planning, organising, conducting, assessing and controlling actions. Dual task abilities, that is the ability to perform successive or simultaneous tasks, are not easy to be evaluated and recovered by traditional paper and pencil methods, due to their ecological and contextual nature. NeuroVR 1.5 is a cost-free virtual reality platform based on open-source software, allowing professionals to easily modify a virtual world, to best suit the needs of the clinical setting.The present study was designed to develop and test a NeuroVR based tool for the rehabilitation of shifting of attention and action planning functions using tasks reminiscent of daily life tasks. We present the virtual environment and the cognitive procedure we developed, discussing two stroke patients case studies, which underwent an integrated neuropsychological and VR assessment.

APS and the nervous system

Cerebrovascular disease is the most frequent clinical manifestation of the antiphospholipid syndrome (APS) at disease onset, after deep venous thrombosis. At a 10-year follow-up, it represents the overall most common clinical event related to antiphospholipid antibodies (aPL). Besides thrombotic events affecting brain circulation, a wide range of “non-criteria” neurological manifestations has been associated with aPL such as dementia, epilepsy, chorea, headache, multiple sclerosis, myelopathy, peripheral neuropathy, hearing loss, and ocular syndromes. aPL display a particular tropism for cerebral circulation, which might be partially explained by the peculiarity of brain endothelial cells. However, aPL might induce neurological manifestations not only because of pro-thrombotic mechanisms but also because they can bind to neurons and astrocytes, disrupting their function. Ischemic manifestations of APS always require the initiation of either antiplatelet drugs or long-term anticoagulants; no standard treatment is available for nonvascular neurological manifestations of APS. The wide heterogeneity in neurological presentation of APS represents a challenge for clinicians: it is important to promptly recognize and effectively treat them in early stages, in order to avoid diagnostic and therapeutic delay.

P1-221: Association between dementia and cancer

the number of episodes. Volumetric assessment of the hippocampus was performed using a 3-dimensional MRI sequence. Total hippocampal volumes were calculated with correction for head size and gender. Subjects with volumes below the 25th percentile of the distribution were defined as having a small hippocampus (n 128). All subjects were followed for development of AD. The diagnosis of AD was made according to internationally accepted criteria. Results: A history of depressive episodes was reported by 142 (27.8%) subjects, with 85 reporting one episode and 50 reporting 2 or more episodes. Logistic regression analyses adjusted for age, gender, education, memory complaints, and MMSE score, showed that subjects with a history of depression were less likely to have a small hippocampus than those without such a history (OR 0.63; 95%CI 0.381.05). The OR of having a small hippocampus associated with 1 episode versus none was 0.74 (95%CI 0.41-1.33) and 2 versus none 0.42 (95%CI 0.18-0.98) (p-trend 0.03). After an average of 6 years of follow-up, 34 subjects developed AD. Cox regression analyses with adjustment for the same covariates showed that subjects with a history of depression had an increased risk of AD (HR 2.42; 95%CI 1.15-5.10). The HR of AD associated with 1 episode versus none was 2.14 (95%CI 0.81-5.64), and 2 versus none 2.54 (95%CI 0.90-7.16) (p-trend 0.04). Conclusion: This study suggests that elderly with a history of depressive episodes are less likely to have a small hippocampus, whereas prospectively they have an increased risk of AD. If replicated, future research should investigate what mechanisms may underly these seemingly contradictory associations.

P2-138: Chemokine serum levels in mild cognitive impairment as Alzheimer’s disease early biomarkers

fluids spans twelve orders of magnitude, with about 90% of the total protein content being represented by only six proteins, that is serum albumin (HSA), IgG, IgA, haptoglobin, antitrypsin and transferrin. Thus, we tested several chromatographic techniques to deplete abundant proteins in human serum and cerebrospinal fluid samples. Whereas HSA can be removed by a blue column or the POROS Affinity Depletion Cartridge (Applied Biosystems, Langen, Germany), it was much more effective to remove several dominant proteins with commercially available affinity columns based on antibodies. The multiple affinity removal system (MARS, Agilent Technologies GmbH, Waldbronn, Germany) quantitatively removed the six most abundant proteins, as mentioned above, and the IgY-12 Proteome Partitioning Spin Column (Beckmann-Coulter GmbH, Unterschlei heim, Germany) removed even twelve abundant proteins. The IgY-12 column depleted besides the six most dominant proteins also IgM, fibrinogen, apolipoprotein (A-I and A-II), -1 acid glycoprotein and -2 macroglobulin from human body fluids. The depleted samples were analyzed by 2-DE followed by western blotting. Specific low-abundant proteins were tested as potential biomarkers with monoclonal antibodies (mAbs) in western-blot analysis to retrieve disease-related spots in the 2D-pattern.