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Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aβ42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Missense mutations were identified in the Grb10-Interacting GYF Protein-2 gene (GIGYF2), located in the chromosomal region 2q36-q37, in familial Parkinson disease (PD) patients of European descent. To determine the contribution of GIGYF2 mutations in an extended (N =305) Belgian series of both familial and sporadic PD patients, we sequenced all 32 coding and non-coding exons of GIGYF2. In three sporadic PD patients we identified two novel heterozygous missense mutations (c.1907A>G, p.Tyr636Cys and c.2501G>A, p.Arg834Gln), that were absent from control individuals (N =360). However, since we lack genetic as well as functional data supporting their pathogenic nature, we cannot exclude that these variants are benign polymorphisms. Together, our results do not support a role for GIGYF2 in the genetic etiology of Belgian PD. [ABSTRACT FROM AUTHOR]

In this publication, we review the activities of the European Uremic Toxin Work Group (EUTox) in the field of uremic toxin research. Founded in 1999 under the umbrella of the European Society of Artificial Organs (ESAO), and active since 2000, this group focuses essentially on questions related to solute retention and removal during chronic kidney disease, and on the deleterious impact of those solutes on biological/biochemical systems. As of January 1, 2009, the group had met 28 times; it organized the third meeting, "Uremic Toxins in Cardiovascular Disease," which took place in October 2008 in Amiens, France. The current group is composed of 25 members belonging to 23 European research institutions. As of November 1, 2008, in total 69 papers had been published to which at least two different research groups belonging to EUTox have contributed in a collaborative effort. Of these, 40 papers were on original research and eight were specific EUTox reviews or position statements. A website (http://www.eutox.info) summarizes all relevant information concerning the work group. EUTox also developed an interactive uremic toxin database, where concentrations of known toxins are displayed, to be used by researchers in the field. In the future, EUTox intends to continue its focus on bench to bedside research with specific consideration of proteomics, metabonomics, secretomics, and genomics.

Background/aims: The aim of this study was to determine the consistency of neuropsychiatric subsyndromes of the Neuropsychiatric Inventory across several clinical and demographic subgroups (e.g. dementia subtypes, dementia severity, medication use, age and gender) in a large sample of outpatients with dementia., Methods: Cross-sectional data of 2,808 patients with dementia from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. Subanalyses were performed for dementia subtypes, dementia severity, medication use, age and gender., Results: The results showed the relatively consistent presence of the 4 neuropsychiatric subsyndromes 'hyperactivity', 'psychosis', 'affective symptoms' and 'apathy' across the subanalyses. The factor structure was not dependent on dementia subtypes, age and gender but was dependent on dementia severity and cholinesterase use. The factors hyperactivity and affective symptoms were present in all subanalyses, but the presence of the factors apathy and psychosis was dependent on use of cholinesterase inhibitors and dementia severity, respectively., Conclusion: The present study provided evidence of the relative consistency of neuropsychiatric subsyndromes across dementia subtypes, age and gender, thereby stressing the importance of thinking about neuropsychiatric subsyndromes instead of separate symptoms. However, the subsyndromes apathy and psychosis were dependent on use of cholinesterase inhibitors and dementia severity., ((c) 2007 S. Karger AG, Basel.)

Background/aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer's disease (AD)., Methods: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis., Results: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients., Conclusion: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD., ((c) 2007 S. Karger AG, Basel.)

Behavioral and psychological symptoms of dementia (BPSD), constitute a major clinical component of Alzheimer's disease (AD). There is a growing interest in BPSD as they are responsible for a large share of the suffering of patients and caregivers, and they strongly determine the patient's lifestyle and management. Better detection and understanding of these symptoms is essential to provide appropriate management. This article is a consensus produced by the behavioral group of the European Alzheimer's Disease Consortium (EADC). The aim of this article is to present clinical description and biological correlates of the major behavioral and psychological symptomatology in AD. BPSD is not a unitary concept. Instead, it should be divided into several symptoms or more likely: groups of symptoms, each possibly reflecting a different prevalence, course over time, biological correlate and psychosocial determinants. There is some clinical evidence for clusters within groups of BPSD. Biological studies indicate that patients with AD and BPSD are associated with variations in the pathological features (atrophy, brain perfusion/metabolism, histopathology) when compared to people with AD without BPSD. An individually tailored approach taking all these aspects into account is warranted as it may offer more, and better, pharmacological and non-pharmacological treatment opportunities.

Introduction: Exploratory pilot studies and knowledge of its mode of action suggested that galantamine, a cholinesterase inhibitor and modulator of nicotinic receptors, can improve attention. This study was designed to test the effects of galantamine on attention in patients with mild-to-moderate Alzheimer's disease (AD) and to see how changes in attention affected their caregivers., Methods: This was an open-label, multicentre study. Patients received galantamine (up to 24 mg/day) for 12 weeks. Attention was assessed after 1, 4, 8 and 12 weeks using computerized tests including Choice Reaction Time (CRT), and caregiver, physician and patient ratings., Results: Data were available from 373 patients (mean age 75 years, mean baseline MMSE score 21). Attention as measured by CRT improved significantly from baseline to study endpoint (p < 0.001), improvements were observed after 1 week and statistical significance was maintained from 8 weeks. Physicians rated 67% of patients as globally improved and 5% as worsened. Caregivers reported improved attention in 57% of patients and worsening in 6%; 62% of patients considered they had improved and 3% considered themselves to be worse. Caregiver stress, time spent caring for patients and patients' interactions with others all improved from baseline to endpoint. Galantamine was generally well tolerated; the most common adverse events were gastrointestinal., Conclusion: Previous controlled trials have demonstrated that galantamine has a positive effect on cognition, activities of daily living, behaviour and global condition, but this is the first study to suggest that galantamine may specifically improve attention (according to both objective and subjective measures) in patients with AD. These effects may be a consequence of galantamine's potentiating action at nicotinic receptors.