Metal pollutant pathways in cohesive coastal catchments: Influence of flocculation and biopolymers on partitioning and flux.

The impacts of the partitioning of potentially toxic metals (PTM) within the estuarine environment is highly complex, but is of key significance owing to increases in populations living within such sensitive environments. Although empirical data exist for the partitioning of metals between the dissolved and particulate phases, little is known regarding the impacts of extracellular polymeric substances (EPS) upon the flocculation of particles within such a dynamic system nor the resultant influence on the distribution of metals between the particulate and dissolved phases. This prevents regulators from fully understanding the fate and risks associated with metals in estuaries. This study provides data associated with the simulation of 3 settlings typical of the turbulent mixing found in estuaries and partitioning of copper, cadmium, nickel, arsenic, lead and zinc for 3 salinities (0, 15, 30 PSU) reflecting the full salinity range from freshwater to seawater. Experiments were completed with and without the presence of EPS, using kaolin as the mineral particulate. The results showed significant differences between salinity, PTMs and turbulence for the experiments with and without EPS present. Overall, salinity was the main factor controlling the PTM partitioning to sediment, however the flocculation process did impact on the PTM distribution and with the addition of EPS the impact was more pronounced. The data highlighted the importance of taking account of EPS within any estuarine sediment process modelling, for relying on simple partitioning with corrections for salinity would likely lead to significant bias.

Report of the task force on designing clinical trials in early (predementia) AD.

BACKGROUND: A large number of promising candidate disease-modifying treatments for Alzheimer disease (AD) continue to advance into phase II and phase III testing. However, most completed trials have failed to demonstrate efficacy, and there is growing concern that methodologic difficulties may contribute to these clinical trial failures. The optimal time to intervene with such treatments is probably in the years prior to the onset of dementia, before the neuropathology has progressed to the advanced stage corresponding to clinical dementia. METHOD: An international task force of individuals from academia, industry, nonprofit foundations, and regulatory agencies was convened to discuss optimal trial design in early (predementia) AD. RESULTS: General consensus was reached on key principles involving the scope of the AD diagnosis, the selection of subjects for trials, outcome measures, and analytical methods. CONCLUSION: A consensus has been achieved in support of the testing of candidate treatments in the early (predementia) AD population.

Study design considerations: conducting global clinical trials in early Alzheimer's disease.

An increasing number of Alzheimer's disease (AD) clinical trials are being conducted in countries in which such trials have infrequently, if ever, been conducted. The infrastructure for conducting trials in many of these regions is not well developed, leading to particular challenges in collection of biomarkers, which are becoming increasingly important in trials in early AD. Linguistic and cultural differences make scale translation, adaptation, validation and implementation across countries and regions difficult. In addition, multiple translations and versions of scales and differences in their administration increase variability and thus decrease the chance of detecting a signal. These issues are magnified in trials in early AD, where detecting subtle neuropsychological deficits is even more challenging. Two additional significant factors for global AD research include: 1) Differing regulatory authority requirements resulting in the need for repeat studies to satisfy diverse regulatory requirements in different parts of the world; and 2) reimbursement and access may be limited due to different data requirements for country specific economic evaluations. While standardization of biochemical assays and neuroimaging protocols have recently been undertaken, there remains a pressing need for standardization of clinical measures (including translation, linguistic and cultural validation and administration). In addition, a global consensus on regulatory requirements for approval of drugs for the treatment of early AD and identification of universally accepted variables from a cost-effectiveness or value perspective would have significant impact on advancing drug development in early AD.

Dementia with cerebrovascular disease: the benefits of early treatment.

Patients with vascular dementia (VaD) and Alzheimer's disease with cerebrovascular disease (AD + CVD) have dementia associated with underlying CVD. Although diagnosis of VaD is challenging, VaD is typically characterized by a stepwise progression of dementia that is closely associated with stroke and focal neurological findings, and a symptom profile that often includes executive dysfunction leading to decreased ability to perform instrumental activities of daily living (IADL). In contrast, AD + CVD patients typically present with progressive deterioration of cognition/memory that may also be influenced by concurrent cerebrovascular events. Early diagnosis and intervention are desirable to prevent further decline due to subsequent vascular events. Management of CVD can limit deterioration of cognitive symptoms in VaD patients, and treatment benefits with cholinesterase inhibitors may be realized as improvement above baseline levels in dementia symptoms. Results from a combined analysis of two 24-week, placebo-controlled clinical trials show that donepezil-treated VaD patients improve in cognition, global function, and performance of IADL. In contrast, AD + CVD patients may continue to decline despite management of CVD, and treatment benefits should be recognized as initial improvements followed by stabilization or slowed decline of dementia symptoms over time. In post-marketing studies, donepezil-treated AD and AD + CVD patients show similar benefits in cognition, global function, and quality of life. The results of these studies support the use of donepezil in treatment of patients with VaD or AD + CVD.

Late-life dementia. Review of the APA guidelines for patient management.

Management of dementia in older patients requires an individualized and multimodal approach that involves use of psychiatric, psychotherapeutic, psychosocial, and somatic tools and treatments, in addition to patient and family education. The progressive nature of dementia and the invariable presence of comorbidity complicates the management task, although symptoms characteristic of dementia's phases can provide helpful clinical clues to guide evolving care. In 1997, the American Psychiatric Association published the "Practice guideline for the treatment of patients with Alzheimer's disease and other dementias of late life." To date, this is the most comprehensive clinical guideline available to physicians caring for patients with Alzheimer's disease and other related dementias.

Associative visual agnosia and alexia without prosopagnosia.

Disagreement over the neuroanatomical substrate of associative visual agnosia encompasses such basic issues as: (1) the necessity for bilateral lesions; (2) the intrahemispheric locus of damage; and (3) the roles of disconnection versus cortical damage. We examined three patients whose associative visual agnosia encompassed objects and printed words but spared faces. CAT scans revealed unilateral dominant occipitotemporal strokes. CAT scans of four previously reported cases with this same profile of associative agnosia were obtained. Dominant parahippocampal, fusiform and lingual gyri were the most extensively damaged cortical regions surveyed and were involved in all cases. Of white matter tracts surveyed, only temporal white matter including inferior longitudinal fasciculus was severely and universally involved. Splenium of the corpus callosum was frequently but not always involved. We conclude there is a form of associative visual agnosia with agnosia for objects and printed words but sparing face recognition which has a characteristic unilateral neuropathology. Damage or disconnection of dominant parahippocampal, fusiform and lingual gyri is the necessary and sufficient lesion.

Anosognosia and visuoverbal confabulation.

OBJECTIVE: To examine the relationship between verbal confabulation and anosognosia for hemiplegia (AHP). DESIGN: We compared patients with right hemisphere lesions and AHP with a control group with right hemisphere lesions without anosognosia. Patients attempted visual identifications of objects exposed to the left hemifield with brief (condition 1) or prolonged (condition 2) presentations. Responses were recorded as correct, incorrect, or admission of failure to perceive. SETTING: Inpatients at Beth Israel Medical Center, New York, NY. PATIENTS: A consecutive sample of nine patients with right hemisphere infarcts who demonstrated left hemiparesis, extrapersonal neglect, and left-sided visual field defects. MAIN OUTCOME MEASURES: Rates of correct, incorrect, and admission of failure to perceive responses. RESULTS: Patients with AHP had higher error rates (confabulations) and lower admission of failure to perceive rates than nonanosognosic patients in condition 1. Patients with AHP continued to have higher error rates in condition 2. Nonanosognosic patients had higher correct rates in condition 2 than condition 1. Groups did not differ in degree of neglect, lesion size or location, atrophy, sensory loss, or disorientation. CONCLUSION: Verbal confabulation is an important determinant in anosognosia.

Two alien hand syndromes.

Review of the clinical characteristics and neuroanatomy of 20 reported cases of alien hand syndrome (AHS) and a patient of our own confirm that AHS is actually two distinct syndromes. Frontal AHS occurs in the dominant hand; is associated with reflexive grasping, groping, and compulsive manipulation of tools; and results from damage to the supplementary motor area, anterior cingulate gyrus, and medial prefrontal cortex of the dominant hemisphere and anterior corpus callosum. Callosal AHS is characterized primarily by intermanual conflict and requires only an anterior callosal lesion. the occurrence of frontal AHS in the dominant limb can be explained by an increased tendency for dominant limb exploratory reflexes coupled with release from an asymmetrically distributed, predominant nondominant-hemisphere inhibition. Callosal AHS is best explained by hemispheric disconnection manifested during behaviors requiring dominant-hemisphere control.