Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model.

Rationale: APP23 mice are a promising model of Alzheimer's disease, expressing several histopathological, cognitive and behavioural hallmarks of the human condition. A valid animal model should respond to therapeutic interventions in an equivalent manner as human patients.

Objectives: To further validate the APP23 model, we examined whether cognitive deficits could be antagonised by donepezil, rivastigmine, galantamine or memantine, which are approved drugs for symptomatic treatment of dementia.

Rivastigmine for dementia associated with Parkinson's disease.

Background: Cholinergic deficits are prominent in patients who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients.

Methods: Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks.

The Middelheim Frontality Score: a behavioural assessment scale that discriminates frontotemporal dementia from Alzheimer's disease.

Background: Despite striking neuropsychological and behavioural differences between Alzheimer's disease (AD) and frontotemporal dementia (FTD), clinical diagnostic criteria failed to discriminate FTD from AD patients. We therefore developed the Middelheim Frontality Score (MFS), a disease-long clinical and behavioural assessment tool that measures frontal lobe features, and set up this prospective study in clinically diagnosed AD and FTD patients to assess discriminatory power and intra- and inter-rater variability.

Methods: Patients with probable AD (n = 400) and FTD (n = 62) were included.

Altered circadian locomotor activity in APP23 mice: a model for BPSD disturbances.

Over the past decade, clinical Alzheimer's disease research has been challenged with an increased interest in noncognitive symptomatology, commonly referred to as behavioural and psychological signs and symptoms of dementia (BPSD). In accordance, major attention is being paid to behavioural alterations in the phenotyping of transgenic mouse models. Besides an age-dependent decline of cognitive functions, the APP23 model was previously shown to exhibit cage activity disturbances, reminiscent of diurnal rhythm disturbances in Alzheimer patients.

Normative data for the Boston Naming Test in native Dutch-speaking Belgian children and the relation with intelligence.

This paper reports the results of a normative study of the 60-item version of the Boston Naming Test (BNT) in a group of 371 native Dutch-speaking Flemish children between the ages of 6 and 12 years. Analysis of test results revealed that BNT performance was significantly affected by age and gender. The gathered norms were shown to be significantly lower than published norms for comparable North-American children.

Behavioral and psychological symptoms in patients with dementia as a target for pharmacotherapy with risperidone.

Objective: To examine the effect of risperidone on specific behavioral and psychological symptoms of dementia (BPSD).

Method: We conducted a post hoc exploratory analysis of an integrated database from 3 randomized, controlled trials of risperidone versus placebo in treating 1150 nursing home residents with BPSD. Changes in scores were measured for items on the Cohen-Mansfield Agitation Inventory (CMAI) and Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD).

Mechanical energy in toddler gait. A trade-off between economy and stability?

Mechanical energy expenditure was investigated in children who are just learning to walk and compared with adult mechanical energy expenditure during walking. First, we determined whether the inverted pendulum (IP) mechanism of energy exchange was present in toddlers. It seems that new walkers partially make use of this energy saving mechanism, but it is less efficient than in adults.

In vitro study of the potential role of guanidines in leukocyte functions related to atherogenesis and infection.

Background: The blunted immune response upon stimulation in chronic renal failure (CRF) is often coupled to a baseline inflammatory status which has been related to atherogenesis. Uremic biologic fluids and several specific uremic retention solutes alter cell-mediated immune responses, as well as the interaction of calcitriol with the immune system.

Methods: The present study evaluated the influence of different guanidino compounds on DNA synthesis, chemiluminescence production, and CD14 expression of undifferentiated and calcitriol-differentiated HL-60 cells.

A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques.

Familial forms of frontotemporal dementia (FTD) with tauopathy are mostly caused by mutations in the gene encoding the microtubule-associated protein tau (MAPT). However, rare forms of familial tauopathy without MAPT mutations have been reported, suggesting other tauopathy-related genetic defects. Interestingly, two presenilin 1 (PS1) mutations (Leu113Pro and insArg352) recently have been associated with familial FTD albeit without neuropathological confirmation.

Plasma guanidino compounds are altered by oral creatine supplementation in healthy humans.

Although creatine is one of the most widely used nutritional supplements for athletes as well as for patients with neuromuscular disorders, the effects of oral creatine supplementation on endogenous creatine synthesis in humans remains largely unexplored. The aim of the present study was to investigate the metabolic consequences of a frequently used, long-term creatine ingestion protocol on the circulating creatine synthesis precursor molecules, guanidinoacetate and arginine, and their related guanidino compounds. For this purpose, 16 healthy young volunteers were randomly divided to ingest in a double-blind fashion either creatine monohydrate or placebo (maltodextrine) at a dosage of 20 g/day for the first week (loading phase) and 5 g/day for 19 subsequent wk (maintenance phase).

Adult crossed aphasia in dextrals revisited.

The clinical study of crossed aphasia in dextrals (CAD) may shed light on the discreteness and modularity of several cognitive functions, such as language, gestures and visual spatial abilities, with respect to hemispheric lateralisation. Since 1975 over 180 cases have been described, employing, however, different criteria of assessment and classification. The purpose of this paper is to review them and to propose a set of diagnostic criteria that may be useful to single out a series of reliable CAD cases on which research can be safely carried out.

Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia.

Background: Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported. Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia (BPSD) in Alzheimer's disease (AD) patients. Given the lack of studies in frontotemporal dementia (FTD) and on folate and given the methodological shortcomings of former publications, we set up a prospective study.

Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency.

We generated a knockout mouse model for guanidinoacetate N-methyltransferase (GAMT) deficiency (MIM 601240), the first discovered human creatine deficiency syndrome, by gene targeting in embryonic stem cells. Disruption of the open reading frame of the murine GAMT gene in the first exon resulted in the elimination of 210 of the 237 amino acids present in mGAMT. The creation of an mGAMT null allele was verified at the genetic, RNA and protein levels.

Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer's disease.

Objectives: Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings.

Methods: Patients (n = 652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.

Cross-national comparison and validation of the Alzheimer's Disease Assessment Scale: results from the European Harmonization Project for Instruments in Dementia (EURO-HARPID).

Background: The Alzheimer's Disease Assessment Scale (ADAS) is often used in international multicenter trials. Use across countries presupposes correct translation and adaptation of the scale, and maintenance of its psychometric properties.

Objectives: To compare the various translations of the ADAS used in Western Europe, to design internationally harmonized translations and to validate these.

Low water-soluble uremic toxins.

The uremic syndrome is the result of the retention of solutes, which under normal conditions are cleared by the healthy kidneys. Uremic retention products are arbitrarily subdivided according to their molecular weight. Low-molecular-weight molecules are characterized by a molecular weight below 500 D.

Cross-national comparisons of the Cambridge Cognitive Examination-revised: the CAMCOG-R: results from the European Harmonization Project for Instruments in Dementia.

Background: Transnational and psychometrically appropriate versions of instruments used in the diagnosis of dementia are essential for comparing information between different countries. The Cambridge Examination for Mental Disorders of the Elderly incorporates a brief neuropsychological test battery, Cambridge Cognitive Examination (recently revised version), which provides objective data on performance across a number of cognitive domains.

Objective: To harmonise the Cambridge Cognitive Examination between seven European countries.

Recurrent transient ischemic attacks in a 15-year-old boy with beta-thalassemia minor and thrombophilia. Contribution of perfusion SPECT to clinical diagnosis.

beta-Thalassemic patients exhibit an increased frequency of thrombotic events but most patients with heterozygous beta-thalassemia minor are asymptomatic and no single case with beta-thalassemia minor and concurrent stroke was reported. We present a 15-year-old boy with heterozygous beta-thalassemia minor who developed recurrent transient ischemic attacks as documented with repeated brain SPECTs whereas structural neuro-imaging was not contributory. The patient exhibited resistance to activated protein C due to heterozygosity for factor V Leiden as well as slightly decreased plasma levels of protein C and S.

Simultaneous electroencephalographic recording and functional magnetic resonance imaging during pentylenetetrazol-induced seizures in rat.

Truly simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) were registered in curarized rats injected with convulsive doses of pentylenetetrazol (PTZ, 65 mg/kg, sc). Rigorous control of physiological parameters like body temperature and ventilation with control of blood gasses helped to avoid potential interference between systemic parameters, and central PTZ-induced blood oxygenation level-dependent (BOLD) changes. Simultaneous EEG/fMRI recordings demonstrated progressive epileptiform EEG discharges with concomitant BOLD changes, the latter gradually affecting most of the fore- and midbrain.

CALL interrupted in a patient with non-specific mental retardation: gene dosage-dependent alteration of murine brain development and behavior.

Investigation of MR patients with 3p aberrations led to the identification of the translocation breakpoint in intron five of the neural Cell Adhesion L1-Like (CALL or CHL1) gene in a man with non-specific mental retardation and 46,Y, t(X;3)(p22.1;p26.3).

On the use of scaling and clustering in the study of semantic deficits.

In the past decade, several studies have used scaling and clustering techniques to document semantic storage deficits in patients with Alzheimer's disease and in schizophrenia. In this article the authors argued that many of the conclusions drawn from these studies are unjustified by the data. They reviewed the methodology used in these studies and presented data from simulation studies to further investigate the validity of their conclusions.

Review on uremic toxins: classification, concentration, and interindividual variability.

Background: The choice of the correct concentration of potential uremic toxins for in vitro, ex vivo, and in vivo experiments remains a major area of concern; errors at this level might result in incorrect decisions regarding therpeutic correction of uremia and related clinical complications.

Methods: An encyclopedic list of uremic retention solutes was composed, containing their mean normal concentration (CN), their highest mean/median uremic concentration (CU), their highest concentration ever reported in uremia (CMAX), and their molecular weight. A literature search of 857 publications on uremic toxicity resulted in the selection of data reported in 55 publications on 90 compounds, published between 1968 and 2002.

Involvement of voltage- and ligand-gated Ca2+ channels in the neuroexcitatory and synergistic effects of putative uremic neurotoxins.

Background: Renal failure has been viewed as a state of cellular calcium toxicity due to the retention of small fast-acting molecules. We have tested this hypothesis and identified potentially neuroexcitatory compounds among a number of putative uremic neurotoxins by examining the acute in vitro effects of these compounds on cultured central neurons. The in vitro neuroexcitatory and synergistic effects of guanidinosuccinate and spermine were also examined in vivo.