NIH toolbox for assessment of neurological and behavioral function.

At present, there are many studies that collect information on aspects of neurologic and behavioral function (cognition, sensation, movement, emotion), but with little uniformity among the measures used to capture these constructs. Further, available measures are generally expensive, normed on homogenous nondiverse populations, not easily administered, do not cover the lifespan (or have easily linked pediatric and adult counterparts for the purposes of longitudinal comparison), and not based on the current thinking in the neuroscience community. There is also a paucity of measurement tools to gauge normal children in the motor and sensation domain areas, and many of these measures rely heavily on proxy reporting.

Assessment of cognition in early dementia.

Better tools for assessing cognitive impairment in the early stages of Alzheimer's disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimer's Association convened a meeting to discuss state of the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory and executive function as among the tools that could provide earlier identification of individuals with AD.

Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.

The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia.

Developing context and background underlying cognitive intervention/training studies in older populations.

Underlying the attempt to change behavior or improve performance by virtue of intervention or training is the notion that change is possible and that plasticity, life-course malleability, and compensation are well-recognized concepts of life-span development. The cognition and aging literature reveals that there are a growing number of context and background variables against which the effectiveness of intervention/training can be judged beyond the intrinsic motivations for change. In this introductory article to a special issue on cognitive intervention and training, we briefly discuss several of these background variables.

The NIH Cognitive and Emotional Health Project. Report of the Critical Evaluation Study Committee.

Background: The Cognitive and Emotional Health Project (CEHP) seeks to identify the demographic, social, and biological determinants of cognitive and emotional health in the older adult. As part of the CEHP, a critical evaluation study committee was formed to assess the state of epidemiological research on demographic, social, and biological determinants of cognitive and emotional health.

Methods: Criteria for inclusion in the survey were large cohort studies, longitudinal in design, participants predominantly 65 years or older, with measurements of both cognition and emotion, and information on a wide variety of demographic, psychosocial, and biological factors.

Depression and Parkinson's disease: a new look at an old problem.

A National Institutes of Health (National Institute of Neurological Disorders and Stroke; National Institute of Mental Health; National Institute on Aging) working group meeting focused on the non-motor aspects of Parkinson's disease (PD). Below is the summary of the meeting presentations and recommendations for a research agenda on the epidemiology, assessment, circuitry, therapeutic approaches, and clinical trials of Parkinson's disease co-morbid with depression. A second summary will focus on PD and dementia.

Comparison of pleural fluid pH values obtained using blood gas machine, pH meter, and pH indicator strip.

Study Purpose: The purpose of this study was to compare the pleural fluid pH values obtained with a blood gas machine (pHbg), with a pH meter (pHmet), and with a pH indicator strip (pHstrip), to determine if the pleural fluid pH measured by a pH meter or a pH indicator strip was sufficiently accurate for clinical decisions.

Methods: The pleural fluid pH was determined, within 20 min after being collected anaerobically, by a blood gas machine (CIBA-Corning model 288), pH meter (Corning pH meter 610A), and pH indicator strip (Baxter Diagnostic) following routine laboratory procedures in 50 pleural fluids. Pleural fluid pH was determined in seven additional samples with the blood gas machine and a pH meter at 25 and 37 degrees C respectively, initially, and after 30 min.

Patients with features similar to Huntington's disease, without CAG expansion in huntingtin.

Objective: To describe characteristics of gene-negative patients with clinical features of Huntington's disease (HD), exploring likely etiologies.

Background: When a direct gene test became definitive for diagnosis of HD, we discovered a number of patients in our clinics in Baltimore, MD, and Cambridge, UK, believed or suspected to have HD who did not have the triplet repeat expansion.

Methods: Patients were examined using standardized instruments, and given full neurologic and psychiatric evaluations.

Frontal lobe volume in patients with Huntington's disease.

Neuropathologic and neuroimaging studies have suggested that frontal lobes are affected in Huntington's disease (HD), and that atrophy in this region may be associated with some of the cognitive impairment and clinical decline observed in patients with HD. We measured gray and white matter volumes within the frontal lobes on MRI for 20 patients with HD (10 mildly affected and 10 moderately affected) and 20 age- and sex-matched control subjects. We also correlated frontal lobe measurements with measures of symptom severity and cognitive function.

Dentatorubral and pallidoluysian atrophy (DRPLA). Clinical and neuropathological findings in genetically confirmed North American and European pedigrees.

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder that clinically overlaps with Huntington's disease (HD) and manifests combinations of chorea, myoclonus, seizures, ataxia, and dementia. DRPLA is caused by a CAG triplet repeat (CTG-B37) expansion coding for polyglutamine on chromosome 12 and exhibits the genetic phenomenon of anticipation. This neurodegenerative disease has only rarely been reported in non-Japanese pedigrees, and there are only a few neuropathological studies in genetically confirmed patients.

Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin.

Huntington's disease (HD) is an inherited neurodegenerative disorder associated with expansion of a CAG repeat in the IT15 gene. The IT15 gene is translated to a protein product termed huntingtin that contains a polyglutamine (polyGln) tract. Recent investigations indicate that the cause of HD is expansion of the polyGln tract.

DRPLA gene (atrophin-1) sequence and mRNA expression in human brain.

Dentatorubral pallidoluysian atrophy (DRPLA, Smith's disease) is one of five disorders currently known to result from expansion of a CAG trinucleotide repeat encoding glutamine. The reported full length cDNA sequence encodes a serine repeat and a region of alternating acidic and basic amino acids, as well as the glutamine repeat. We now report the nucleic acid and deduced amino acid sequences of the open reading frame of this gene, obtained from a series of independently isolated and sequenced cDNA clones.

Expression of the Huntington's disease (IT15) protein product in HD patients.

Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by expansion of a CAG repeat in the IT15 gene, leading to an expanded glutamine repeat in the HD protein. The mechanism by which the expanded repeat causes expression of the disease is not known, though there do not appear to be changes in the mRNA levels. We have conducted quantitative Western blot analyses of HD patients and controls.

Widespread expression of Huntington's disease gene (IT15) protein product.

Huntington's Disease (HD) is caused by expansion of a CAG repeat within a putative open reading frame of a recently identified gene, IT15. We have examined the expression of the gene's protein product using antibodies developed against the N-terminus and an internal epitope. Both antisera recognize a 350 kDa protein, the predicted size, indicating that the CAG repeat is translated into polyglutamine.

Expression of the mutant allele of IT-15 (the HD gene) in striatum and cortex of Huntington's disease patients.

Huntington's disease (HD) is an inherited neurodegenerative disorder expressed when a trinucleotide repeat in the gene IT-15 is expanded. The mechanism by which the expanded repeat causes the expression of the disease is unknown. Possible mechanisms include alterations in the amount of the mRNA, potentially resulting from changes in gene transcription or abnormal mRNA stability.

Selective loss of [3H]kainic acid and [3H]AMPA binding in layer VI of frontal cortex in Huntington's disease.

Excitatory amino acid neurotoxicity has been proposed to cause the neostriatal neuronal degeneration of Huntington's disease (HD); N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate receptors have been hypothesized to play important roles in this process. We have recently reported a loss of neurons in layer VI of the cerebral cortex in HD. Using quantitative autoradiographic methods, we have now measured NMDA, AMPA, and kainate receptor binding in the frontal cerebral cortex of the brains of controls and individuals with HD.