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PubMed2026

Plasma von Willebrand Factor and ADAMTS13 Interact With APOE-ε4 in Predicting Longitudinal Brain Atrophy and Cognitive Decline Over a 9-Year Follow-Up.

BACKGROUND: Von Willebrand factor (VWF) and ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) are linked to dementia risk, and limited evidence suggests apolipoprotein E (APOE)-&#x3b5;4 alters VWF release. This study assessed whether baseline VWF and ADAMTS13 levels predict neurodegeneration and cognitive decline and evaluated effect modification by APOE-&#x3b5;4 carriership. METHODS: Vanderbilt Memory and Aging Project cohort participants (n=332, 73&#xb1;7&#x2009;years, 59% male) completed serial blood draw, neuropsychological assessment, and brain magnetic resonance imaging over 6.4&#x2009;years (range 1.4-9.7&#x2009;years). Baseline plasma VWF and ADAMTS13 levels were quantified using mass spectrometry and Olink. Fully adjusted linear mixed-effects models related protein&#xd7;time and protein&#xd7;APOE-&#x3b5;4&#xd7;time interaction terms to longitudinal brain magnetic resonance imaging and neuropsychological outcomes. RESULTS: Lower baseline ADAMTS13 predicted faster declines in language (&#x3b2;=0.11, P=0.01), information processing speed (&#x3b2;=0.27, P=0.001), executive function (&#x3b2;=0.01, P=0.03), episodic memory (&#x3b2;=0.01, P=0.03), and visuospatial ability (&#x3b2;=0.11, P=0.001) and faster increases in global (&#x3b2;=-0.29, P=0.01) and frontal (&#x3b2;=-0.17, P=0.01) white matter hyperintensity volumes. Associations between ADAMTS13 and faster rates of cognitive decline and white matter injury were driven by APOE-&#x3b5;4 carriers. Models relating VWF to longitudinal outcomes were null. APOE-&#x3b5;4 interacted with VWF on longitudinal gray matter volumetric outcomes, such that faster rates of global gray matter atrophy were observed with higher baseline VWF levels among APOE-&#x3b5;4 noncarriers only (&#x3b2;=-1530.5, P<0.001). CONCLUSIONS: ADAMTS13 shows promise as a potential plasma biomarker for brain aging outcomes, but additional research is warranted to understand the performance of VWF in the presence versus absence of an APOE-&#x3b5;4 allele.

Humans↗
PubMed1991

Attention deficit hyperactivity disorder-residual type.

Evidence for the persistence into adult life of attention deficit hyperactivity disorder (ADHD) has accumulated in publications of the past two decades. As reviewed here, retrospective and longitudinal data suggest that a residual type of ADHD (ADHD-RT) can be recognized. Diagnostic historical interview and checklist criteria, primarily the Utah set developed by Wender and colleagues, have been proposed. The difficulties of obtaining reliable and valid historical information, which are greater than those encountered in diagnosing childhood cases, add to the desirability of some direct examination for ADHD-RT. It is proposed herein that assessment of the neuropsychological domain of executive function--broader than, yet encompassing, several facets of attention--offers opportunities for documentation of the cognitive correlates of ADHD-RT, its responsiveness to therapeutic intervention, and clues as to its neurobiological foundation.

Adult↗
PubMed1989

The spectrum of imaging and neuropsychological findings in Pick's disease.

To seek improved methods for the diagnosis of Pick's disease, we reviewed imaging studies of four women and two men (ages 48 to 65 years at onset) and psychometric testing of three of them with autopsy or biopsy-proved Pick's. The presence of Pick bodies was required for the diagnosis. Seven patients with biopsy-proved Alzheimer's disease served as a comparison group. In the Pick's patients, CT in five of six showed marked frontal pole or temporal pole atrophy, which clearly differed from the pattern of cerebral atrophy seen in the Alzheimer's patients. Psychometric testing showed performance patterns that tended to differ from those of the Alzheimer's patients in that recent memory was relatively preserved despite marked impairment of executive functions. The distinctive psychometric pattern in the Pick's patients was evanescent, however. Thus, there were imaging and psychometric findings of potential diagnostic value for Pick's disease, but, for different reasons, they were imperfect.

Aged↗
PubMed1983

The new Israeli health care reform: an analysis of a national need.

This paper describes the current situation of health care services in Israel. Major problems are discussed and analyzed in terms of the dualism of the main health organizations (the Ministry of Health and the General Sickness Fund), the multiplicity and discontinuity of health care delivery, quality-of-care problems, and the uneven geographical distribution of facilities. A proposal for a reform of the health care system is outlined, and its principles enumerated. This reform, suggested by the Ministry of Health, reflects a new approach of separating the direct provision of care from the executive functions of planning and control of services. The Ministry's proposal is analyzed, and its implications are discussed in relation to the American health care system.

Delivery of Health Care↗
PubMed1986

Beyond language--speculations on the prefrontal cortex and schizophrenia.

Changes to the structural complexity of the spoken language of schizophrenic patients have been demonstrated in three recent studies. The speculation is offered that these changes could result from dorsolateral prefrontal cortical dysfunction. Impairment of the executive functions of this part of the brain could theoretically explain both the varied symptomatology of schizophrenia and its unique pattern of ages of onset.

Age Factors↗
PubMed1992

Cognitive impairments in Parkinson's disease.

The clinical neuropsychologic profiles of patients with Parkinson's disease and patients with SDAT show both overlap and dissociation. Speech, language, and certain memory skills are examples of dissociable differences, especially in the early stages of the disease. Furthermore the presence of depression, evidence of cognitive slowing, and absence of aphasia in patients with Parkinson's disease suggest prominent subcortical involvement. It is probably premature to categorize all of the cognitive changes in patients with Parkinson's disease as subcortical, however. Some skills, such as visuospatial and executive functions, are impaired in both disorders, and although the etiologic bases for task failure may differ for each, this issue remains open-ended. Another problem is that often the evidence for or against the cortical/subcortical distinction is insufficient and in some cases based on a single measure thought to be representative of a given cognitive domain. Most importantly there are few comparative studies that provide unequivocal support for making a cortical/subcortical distinction. Failure to equate for level of cognitive impairment or functional disability between dementias and strict adherence to cross-sectional study designs further compromise efforts to characterize each syndrome precisely. Whitehouse suggested that a prospective study of several different dementias studied in parallel, examining a wide range of cognitive skills, is required before the cortical/subcortical classification scheme can be validated. A critical component is an autopsy program to confirm diagnoses and provide clinicopathologic correlation. It is possible that the diverse nature of the cognitive impairment in patients with Parkinson's disease is not a methodologic artifact but reflects multiple disease subtypes. Ross, Mahler, and Cummings proposed three dementia syndromes in patients with Parkinson's disease: one that is relatively mild and meets the criteria for subcortical dementia, a second that is more severe and shows a wider range of cognitive impairment but is still neuropathologically distinct from SDAT, and a third severe dementia with both subcortical and cortical involvement that may reflect basal ganglia and Alzheimer-type pathology.

Cognition Disorders↗
PubMed1992

Bedside assessment of executive cognitive impairment: the executive interview.

OBJECTIVE: This study is a pilot validation of the Executive Interview (EXIT), a novel instrument designed to assess executive cognitive function (ECF) at the bedside. DESIGN: Inter-rater reliability testing and validation using inter-group comparisons across levels of care and measures of cognition and behavior. PARTICIPANTS: Forty elderly subjects randomly selected across four levels of care. SETTING: Settings ranged from independent living apartments to designated Alzheimer's Special Care units in a single 537-bed retirement community. MEASUREMENTS: The EXIT: a 10-minute, 25-item interview scored from 0-50 (higher scores = greater executive dyscontrol) was administered by a physician. Subjects were also administered the Mini-Mental State Exam (MMSE) and traditional tests of "frontal" executive function by a neuropsychologist, and the Nursing Home Behavior Problem Scale (NHBPS) by Licensed Vocational Nurses. RESULTS: Interrater reliability was high (r = .90). EXIT scores correlated well with other measures of ECF. The interview discriminated among residents at each level of care. In contrast, the MMSE did not discriminate apartment-dwelling from residential care residents, or residential care from nursing home residents. The EXIT was highly correlated with disruptive behaviors as measured by the NHBPS (r = .79). CONCLUSIONS: These preliminary findings suggest that the EXIT is a valid and reliable instrument for the assessment of executive impairment at the bedside. It correlates well with level of care and problem behavior. It discriminates residents at earlier stages of cognitive impairment than the MMSE.

Aged↗
PubMed1984

The nurse executive role. A structural and functional analysis.

This study analyzes the structure and functions of the position of nurse executives to determine competencies required in the role, to provide a base for planning educational programs, and to identify areas for future research. These nurse executives have a dynamic role, one that has evolved as a result of role making on their part. In interviews they show a concern for meeting society's nursing needs. The interviews also show that in their positions at the executive level of the organization, they deal with complex patterns of interactional behaviors and have an ever-evolving role as the organization's power structure changes. Implications emerge for educational preparation that will help executives in their roles as nurse, administrator, and educator/researcher.

Administrative Personnel↗
PubMedDate not supplied

Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions.

The cingulate gyrus is a major part of the "anatomical limbic system" and, according to classic accounts, is involved in emotion. This view is oversimplified in light of recent clinical and experimental findings that cingulate cortex participates not only in emotion but also in sensory, motor, and cognitive processes. Anterior cingulate cortex, consisting of areas 25 and 24, has been implicated in visceromotor, skeletomotor, and endocrine outflow. These processes include responses to painful stimuli, maternal behavior, vocalization, and attention to action. Since all of these activities have an affective component, it is likely that connections with the amygdala are critical for them. In contrast, posterior cingulate cortex, consisting of areas 29, 30, 23, and 31, contains neurons that monitor eye movements and respond to sensory stimuli. Ablation studies suggest that this region is involved in spatial orientation and memory. It is likely that connections between posterior cingulate and parahippocampal cortices contribute to these processes. We conclude that there is a fundamental dichotomy between the functions of anterior and posterior cingulate cortices. The anterior cortex subserves primarily executive functions related to the emotional control of visceral, skeletal, and endocrine outflow. The posterior cortex subserves evaluative functions such as monitoring sensory events and the organism's own behavior in the service of spatial orientation and memory.

Amygdala↗
PubMed1986

[Usefulness of radioisotopic methods in the study of the salivary glands].

The results achieved by dynamic and static salivary gland scintigraphy in 272 patients over a ten year time (January 1976-December 1985) are reported. On the basis of a semi-quantitative assessment of time/activity curves, dynamic studies prove to be the most suitable method for studying functional disorders (phlogosis, facial paralysis, etc.). Harmlessness, easy execution and functional results are the main advantages of radioisotope techniques. Salivary gland scintigraphy has some limits in the study of space occupying lesions (SOL): however, ultrasounds, CT and sialography represent the methods of choice in this field of salivary gland pathology.

Acute Disease↗
PubMed1990

Pretreatment neuropsychological status and associated factors in children with primary brain tumors.

We report on the neuropsychological status of 31 children with primary brain tumors who underwent assessment before receiving therapy. Overall, the children performed within normal limits in all test areas. The exception was the group with anterior hemispheric tumors who demonstrated deficits in executive cognitive functions. Also, when compared according to tumor type, children with midline tumors and hydrocephalus performed more poorly than others on measures of intelligence, executive abilities, visual-motor skills, and fine-motor functions. Although one-half to two-thirds of the children with supratentorial midline and infratentorial tumors had cranial nerve, oculomotor, or cerebellar deficits, only the latter were associated with specific neuropsychological deficits (poorer performance on fine-motor and visual-motor tests). Age did not appear to be a factor in these children's neuropsychological test performances.

Adolescent↗
PubMed1990

GAL4 mutations that separate the transcriptional activation and GAL80-interactive functions of the yeast GAL4 protein.

The carboxy-terminal 28 amino acids of the Saccharomyces cerevisiae transcriptional activator protein GAL4 execute two functions--transcriptional activation and interaction with the negative regulatory protein, GAL80. Here we demonstrate that these two functions are separable by single amino acid changes within this region. We determined the sequences of four GAL4C-mutations, and characterized the abilities of the encoded GAL4C proteins to activate transcription of the galactose/melibiose regulon in the presence of GAL80 and superrepressible GAL80S alleles. One of the GAL4C mutations can be compensated by a specific GAL80S mutation, resulting in a wild-type phenotype. These results support the idea that while the GAL4 activation function tolerates at least minor alterations in the GAL4 carboxyl terminus, the GAL80-interactive function is highly sequence-specific and sensitive even to single amino acid alterations. They also argue that the GAL80S mutations affect the affinity of GAL80 for GAL4, and not the ability of GAL80 to bind inducer.

Alleles↗