Cognitive evaluation of disease-modifying efficacy of galantamine and memantine in the APP23 model.

With increasing knowledge of molecular, biochemical and cellular events causing synaptic dysfunction and neurodegeneration in Alzheimer-diseased brain, preventive treatment strategies are emerging. Neuroprotective capacities have been attributed to galantamine and memantine. The age-dependent cognitive decline in the APP23 model was employed to evaluate disease-modifying efficacy of chronic treatment with both compounds.

A role for the cerebellum in motor speech planning: evidence from foreign accent syndrome.

A 3 year follow-up study was performed in a patient with foreign accent syndrome (FAS) as the sole cognitive manifestation of a left fronto-parietal stroke. The hypothesis of involvement of the right cerebellum in this motor speech planning disorder was investigated by means of functional neuroimaging (SPECT) and neurobehavioral assessments. Based on the close parallelism between the evolution of FAS symptoms and the perfusional changes in the right cerebellum, it is argued that FAS may result from a disruption of a close functional interplay between the supra- and infratentorial speech centers involved in motor speech planning.

Management of agitation, aggression, and psychosis associated with dementia: a pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone.

This analysis used pooled data from three randomized, placebo-controlled trials that examined the efficacy and safety of risperidone for the treatment of agitation, aggression, and psychosis associated with dementia in elderly nursing home residents to assess the risk-benefit of the use of risperidone in this population. The efficacy data (risperidone n=722, placebo n=428) were obtained from the Cohen-Mansfield agitation inventory (CMAI) and behavioral pathology in Alzheimer's disease (BEHAVE-AD) total and subscales. Additionally, clinical global impression (CGI) assessments were performed.

Cognitive decline, neuromotor and behavioural disturbances in a mouse model for fragile-X-associated tremor/ataxia syndrome (FXTAS).

Carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are spared the major neurodevelopmental symptomatology of fragile X syndrome patients carrying a full mutation (>200 repeats). In a proportion of premutation carriers, the repeat expansion is associated with a specific neurological profile involving intention tremor, ataxia, intellectual decline compatible with dementia syndrome, Parkinsonism and autonomic dysfunction at older age, commonly referred to as fragile-X-associated tremor/ataxia syndrome (FXTAS). Typical CNS changes include hyperintense signals on T2 weighted magnetic resonance images and the presence of ubiquitin-positive intranuclear neuronal inclusions.

Paced visual serial addition test in multiple sclerosis.

The paced auditory serial addition test (PASAT), a subtest of the multiple sclerosis functional composite score (MSFC), is increasingly used in the evaluation of cognitive function in multiple sclerosis (MS). While patient acceptance for the PASAT is low, its visual version, the paced visual serial addition test (PVSAT), is perceived to be better tolerated. The aim of this study was to investigate the interchangeability of PVSAT and PASAT in the evaluation of cognitive function in MS.

Biochemical and behavioural phenotyping of a mouse model for GAMT deficiency.

Deficiency of guanidinoacetate N-methyltransferase (GAMT) is the first described creatine (CT) deficiency syndrome in man, biochemically characterized by accumulation of guanidinoacetic acid (GAA) and depletion of CT. Patients exhibit severe developmental and muscular problems. We created a mouse model for GAMT deficiency, which exerts biochemical changes comparable with those found in human GAMT-deficient subjects.

Kinetic behavior of urea is different from that of other water-soluble compounds: the case of the guanidino compounds.

Background: Although patients with renal failure retain a large variety of solutes, urea is virtually the only currently applied marker for adequacy of dialysis. Only a limited number of other compounds have up until now been investigated regarding their intradialytic kinetics. Scant data suggest that large solutes show a kinetic behavior that is different from urea.

APP23 mice as a model of Alzheimer's disease: an example of a transgenic approach to modeling a CNS disorder.

Animal models are considered essential in research ensuing elucidation of human disease processes and subsequently, testing of potential therapeutic strategies. This is especially true for neurodegenerative disorders, in which the first steps in pathogenesis are often not accessible in human patients. Alzheimer's disease is vastly becoming a major medical and socioeconomic problem in our aging society.

Analysis of cholinergic markers, biogenic amines, and amino acids in the CNS of two APP overexpression mouse models.

Two transgenic mouse models expressing mutated human amyloid precursor protein and previously found to display cognitive and behavioural alterations, reminiscent of Alzheimer patients' symptomatology, were scrutinised for putative brain region-specific changes in neurochemical parameters. Brains of NSE-hAPP751m-57, APP23 and wild-type mice were microdissected to perform brain region-specific neurochemical analyses. Impairment of cholinergic transmission, the prominent neurochemical deficit in Alzheimer brain, was examined; acetylcholinesterase and choline acetyltransferase activity levels were determined as markers of the cholinergic system.

GSA: behavioral, histological, electrophysiological and neurochemical effects.

Renal insufficient patients suffer from a variety of complications as direct and indirect consequence of accumulation of retention solutes. Guanidinosuccinic acid (GSA) is an important probable uremic toxin, increased in plasma, urine, cerebrospinal fluid and brain of patients with uremia and supposed to play a role in the pathogenesis of some neurological symptoms. GSA, an NMDA-receptor agonist and GABA-receptor antagonist, is suggested to act as an excitotoxin and shown to be convulsive.

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).

Guanidinium chloride denaturation of the dimeric Bacillus licheniformis BlaI repressor highlights an independent domain unfolding pathway.

The Bacillus licheniformis 749/I BlaI repressor is a prokaryotic regulator that, in the absence of a beta-lactam antibiotic, prevents the transcription of the blaP gene, which encodes the BlaP beta-lactamase. The BlaI repressor is composed of two structural domains. The 82-residue NTD (N-terminal domain) is a DNA-binding domain, and the CTD (C-terminal domain) containing the next 46 residues is a dimerization domain.

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.