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Cognitive resemblance in reading-disabled twins.

This study examined the cognitive abilities of 60 pairs of reading-disabled twins aged between eight and 18 years (at least one member of each twin pair had been diagnosed as having a reading disability). Principal component analysis of nine cognitive tests yielded three readily interpretable composites of cognitive abilities--reading, symbol-processing speed and sequential memory. Scores on these three cognitive composites were significantly lower for the disabled readers than for normal readers. Individual differences in these cognitive composites within the reading-disabled twin sample were found to be due to genetic differences. Furthermore, deficits in the reading composite for the reading-disabled sample appear to be heritable.

Adolescent

Auditive and cognitive factors in speech perception by elderly listeners. I: Development of test battery.

This study compares performance of 24 young normal-hearing (aged 18-28 years) and 24 elderly (aged 61-85 years) listeners on auditive (sensitivity, frequency selectivity, and temporal resolution), cognitive (memory performance, processing speed, and divided attention ability), and speech perception tests (at the phoneme, spondee, and sentence level). Its principal aim is to assess whether the tests selected yield meaningful results. The results obtained will be used to reduce the test battery in order to be manageable in a second study on a much larger number of elderly listeners. The relationships between the tests are explored by multivariate statistical methods. The results show that: (a) in young listeners, individual differences in speech perception performance are remarkably small resulting in low correlations between the tests, while in the elderly tests of phoneme, spondee, and sentence perception overlap considerably; (b) speech perception in the elderly seems to be largely determined by hearing loss at the higher frequencies, whereas the effects of other auditive and cognitive factors seem to be relatively small or absent; and (c) performance in the elderly is only partly correlated with age.

Acoustic Stimulation

Auditive and cognitive factors in speech perception by elderly listeners. II: Multivariate analyses.

In part I of this study [van Rooij et al., J. Acoust. Soc. Am. 86, 1294-1309 (1989)], the validity and manageability of a test battery comprising auditive (sensitivity, frequency resolution, and temporal resolution), cognitive (memory performance, processing speed, and intellectual abilities), and speech perception tests (at the phoneme, spondee, and sentence level) were investigated. In the present article, the results of a selection of these tests for 72 elderly subjects (aged 60-93 years) are analyzed by multivariate statistical techniques. The results show that the deterioration of speech perception in the elderly consists of two statistically independent components: (a) a large component mainly representing the progressive high-frequency hearing loss with age that accounts for approximately two-thirds of the systematic variance of the tests of speech perception and (b) a smaller component (accounting for one-third of the systematic variance of the speech perception tests) mainly representing a general performance decrement due to reduced mental efficiency, which is indicated by a general slowing of performance and a reduced memory capacity. Although both components are correlated with age, it was found that the balance between auditive and cognitive contributions to speech perception performance did not change with age.

Adolescent

Psychomotor slowing and subcortical-type dysfunction in depression.

Elderly patients with major depression and normal controls completed the Sternberg short-term memory scanning procedure and WAIS Digit Symbol. Depressed patients demonstrated psychomotor slowing on both tasks, but normal response latency as a function of memory set size on the Sternberg procedure. While cognitive-behavioural slowing may be observed in both depressive illness and subcortical neurological disorders, a normal rate of processing information centrally appears to distinguish depression from certain of these disorders. Psychomotor slowing in the presence of normal information processing speed might be explained by a deficit in motivational state associated with depression.

Aged

Increased radiation dose at mammography due to prolonged exposure, delayed processing, and increased film darkening.

Four single-emulsion films introduced over the past 2 years--Du Pont Microvision, Fuji MiMa, Konica CM, and Eastman Kodak OM--were compared with Eastman Kodak OM SO-177 (Min-RE) film to evaluate their varying effects on mean glandular dose of reciprocity law failure due to prolonged exposure, delayed processing, and increased film darkening as a result of increased radiation exposure to improve penetration of glandular tissue. Exposures over 1.3 seconds led to increased radiation doses of 20%-30%. Delays in processing of 6 hours decreased processing speed by 11%-32% for all films except Du Pont Microvision. Optical density increases of 0.40 required 20%-30% more skin exposure for all five films. Optimal viewing densities were also evaluated and found to be different for each of the five films. Mammographers need to be aware of these differences in mammographic films to achieve maximum contrast at mammography.

Breast

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

Free-water: A promising structural biomarker for cognitive decline in aging and mild cognitive impairment.

Diffusion MRI derived free-water (FW) metrics show promise in predicting cognitive impairment and decline in aging and Alzheimer's disease (AD). FW is sensitive to subtle changes in brain microstructure, so it is possible these measures may be more sensitive than traditional structural neuroimaging biomarkers. In this study, we examined the associations among FW metrics (measured in the hippocampus and two AD signature meta-ROIs) with cognitive performance, and compared FW findings to those from more traditional neuroimaging biomarkers of AD. We leveraged data from a longitudinal cohort (nparticipants = 296, nobservations = 870, age at baseline: 73 &#xb1; 7 years, 40% mild cognitive impairment [MCI]) of older adults who underwent serial neuropsychological assessment (episodic memory, information processing speed, executive function, language, and visuospatial skills) and brain MRI over a maximum of four time points, including baseline (n = 284), 18-month (n = 246), 3-year (n = 215), and 5-year (n = 125) visits. The mean follow-up period was 2.8 &#xb1; 1.3 years. Structural MRI was used to quantify hippocampal volume, in addition to Schwarz and McEvoy AD Signatures. FW and FW-corrected fractional anisotropy (FAFWcorr) were quantified in the hippocampus (hippocampal FW) and the AD signature areas (SchwarzFW, McEvoyFW) from diffusion-weighted (dMRI) images using bi-tensor modeling (FW elimination and mapping method). Linear regression assessed the association of each biomarker with baseline cognitive performance. Additionally, linear mixed-effects regression assessed the association between baseline biomarker values and longitudinal cognitive performance. A subsequent competitive model analysis was conducted on both baseline and longitudinal data to determine how much additional variance in cognitive performance was explained by each biomarker compared to the covariate only model, which included age, sex, race/ethnicity, apolipoprotein-&#x3b5;4 status, cognitive status, and modified Framingham Stroke Risk Profile scores. All analyses were corrected for multiple comparisons using an FDR procedure. Cross-sectional results indicate that hippocampal volume, hippocampal FW, Schwarz and McEvoy AD Signatures, and the SchwarzFW and McEvoyFW metrics are all significantly associated with memory performance. Baseline competitive model analyses showed that the McEvoy AD Signature and SchwarzFW explain the most unique variance beyond covariates for memory (&#x394;Radj 2 = 3.47 &#xb1; 1.65%) and executive function (&#x394;Radj 2 = 2.43 &#xb1; 1.63%), respectively. Longitudinal models revealed that hippocampal FW explained substantial unique variance for memory performance (&#x394;Radj 2 = 8.13 &#xb1; 1.25%), and outperformed all other biomarkers examined in predicting memory decline (pFDR = 1.95 x 10-11). This study shows that hippocampal FW is a sensitive biomarker for cognitive impairment and decline, and provides strong evidence for further exploration of this measure in aging and AD.

Alzheimer&#x2019;s disease (AD)

Self-reported visual problems of older drivers.

We conducted a survey in order to gain insights into the reasons older persons decide to give up driving. Our survey focused on vision. We probed the relationship between visual deficiencies and driving status by asking older people about the problems they encountered while performing routine visual tasks. The results showed that older persons who had recently given up driving reported more visual problems than did their driving counterparts. These problems related to difficulties in dynamic vision, visual processing speed, visual search, light sensitivity, and near vision. The results suggested that older persons are sensitive to their own visual deficits and that this awareness influences decisions about driving.

Activities of Daily Living

Neuropsychologic test performance in amateur boxers.

Cognitive functions of 23 amateur boxers were assessed immediately before and after an amateur boxing event. A range of cognitive measures were employed including tasks of verbal, figural, and incidental memory, motor functions, attention and concentration, and information processing speed. Compared to their prefight performance, boxers demonstrated impairments in verbal and incidental memory, but enhanced executive and motor functions postfight. There were no observed differences between winners and losers on any of the measures. The results are compared to other studies that have shown only minor changes in cognitive functions in amateur boxers compared to controls.

Adolescent

Cluster analysis applied to symptom ratings of psychiatric patients: an evaluation of its predictive ability.

Rating on 39 symptoms were examined for patients admitted to the Neuropsychiatric Institute of the University of Michigan Medical Center. A detailed evaluation was made of the clusters derived by a hierarchical clustering algorithm, using complete linkage and a simple matching coefficient on the binary variables of presence or absence of symptoms. The four groups of patients suggested by the cluster analysis can be characterized as follows: (1) generalized multiplicity of symptoms; (2) capacity to cope except for orientation apart from generally held norms; (3) activity level and thought processes speeded up, intensified, and unselected; (4) inwardly punitive, slowed down and distressed. It is shown that these groups received significantly different treatment and that the effect of treatment was significantly different, while no such differences were noted for groups defined in terms of diagnoses. By means of linear discriminant functions, rules are suggested for assigning other psychiatric patients to one of these four groups.

Antipsychotic Agents

The effect of neuroleptics on cognitive and psychomotor function. A preliminary study in healthy volunteers.

The effects of haloperidol (1 mg), benzhexol (5 mg), diazepam (10 mg) and caffeine (400 mg) on subjective and objective measures of cognitive and psychomotor function were compared with placebo in 20 healthy volunteers. While both diazepam and benzhexol were associated with highly significant impairments in subjective altertness, critical flicker fusion threshold and choice reaction time (CRT), haloperidol could not be distinguished from placebo in most tests but was actually associated with an apparent improvement in CRT (in males) and simple visual reaction time. The perceptual maze test detected impairment by benzhexol on processing speed but was not sensitive to any other drug effects. Multiple-dose studies are required to establish if there is a true activating effect of haloperidol using a test of sustained attention. No effect of Eysenck personality subtype or life events on baseline or drug response data was detected.

Adult

The Edinburgh cohort of HIV-positive drug users: pattern of cognitive impairment in relation to progression of disease.

To examine the neuropsychiatric effects of infection with HIV, 220 drug users (27 HIV negative, 193 HIV positive) completed tests evaluating premorbid intelligence, memory, non-verbal performance, information processing speed, and mood. When these measures were compared cross-sectionally by the severity of HIV illness, symptomatic patients (in CDC stage IV) were impaired on Trails B, two-choice decision time, delayed recall of the Wechsler Logical Memory Test and most components of the Auditory Verbal Learning Test. These findings imply reduced capacity for concentration, speed of thought and memory. When 101 patients were retested a mean of 16 months after their initial assessment, performance on Trails A and B, Block Design and delayed recall of the Wechsler Logical Memory Test deteriorated more for patients at, or progressing within, CDC stage IV, than performance of patients at stage III. The results broadly correspond to the cross-sectional findings. However, there was a decline in all tests of memory function for the sample independent of clinical staging. This may be evidence of brain involvement before the appearance of other symptoms. Self-rated measures of mood did not change cross-sectionally, progressively, or interactively with time and stage of HIV illness, and cannot account for the changes in cognitive function observed. Change in drug use, similarly, does not account for the cognitive findings. Four (5%) of the retested subjects developed AIDS dementia complex, but most of the performance and memory impairments seen were subclinical despite the destructive neuropathology presumed to underlie intellectual decline in patients with HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex

Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis.

Previous research has suggested that cerebral lesions observed on magnetic resonance imaging (MRI) of MS patients are clinically "silent." We examined the validity of this assertion by correlating neuropsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables: total lesion area (TLA), ventricular-brain ratio (VBR), and size of the corpus callosum (SCC). Stepwise multiple regression analyses indicated that TLA was a robust predictor of cognitive dysfunction, particularly for measures of recent memory, abstract/conceptual reasoning, language, and visuospatial problem solving. SCC predicted test performance on measures on mental processing speed and rapid problem solving, while VBR did not independently predict cognitive test findings. These findings suggest that cerebral lesions in MS produce cognitive dysfunction and that MRI may be a useful predictor of cognitive dysfunction.

Brain

Signs of cognitive change in HIV disease: an event-related brain potential study.

We recorded event-related brain potentials (ERPs) from 2 groups of human immunodeficiency virus (HIV)-positive men with no physical illness or neurologic involvement: 9 asymptomatic (AS+) and 9 classified as having either acquired immunodeficiency syndrome (AIDS; 7) or AIDS-related complex (ARC; 2). In separate choice reaction time tasks, the subjects pressed buttons to randomly presented auditory or visual stimuli at probabilities of either 20/80 or 50/50. There were no group differences on any of the neuropsychological tests commonly used in screening batteries for HIV patients. In contrast, reduced P300 amplitudes and increased P300 latencies occurred in ARC/AIDS patients in response to both auditory and visual stimuli, while in AS+ patients such alterations occurred only in the visual modality. Significant delays in P2 latency were found only in the auditory modality and then only in ARC/AIDS patients. ARC/AIDS patients alone showed delayed response times, and only in the auditory modality. The P300 results demonstrate alterations in stimulus evaluation and processing speed in the earliest stages of HIV disease, even before cognitive deficits can be detected by more traditional measures.

AIDS-Related Complex

Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene.

We present prospective clinical and neuropathologic details of a pedigree segregating familial Alzheimer's disease (FAD) associated with a mutation (G----A substitution) at nucleotide 2149 in exon 17 of the amyloid precursor protein (APP) gene. This mutation, which is predicted to cause the missense substitution of isoleucine for valine at codon 717 of APP, cosegregated perfectly with the FAD trait (lod score = 3.49 at theta = 0.00). The earliest clinical manifestations of the disease relate to deficits in memory function, cognitive processing speed, and attention to complex cognitive sets. These changes occurred in the absence of changes in nonmemory language and visuospatial functions. The neuropathologic features of FAD associated with the APP717 mutation in this family include severe neuronal loss, abundant neurofibrillary tangles, amyloid plaques, and amyloid angiopathy. These results provide independent confirmation that mutations in the APP gene are linked to the FAD trait in some families.

Adult

Multifactorial assessment of reading disability: identifying the best predictors.

A multifactorial diagnostic assessment battery was evaluated using data obtained from 105 reading-disabled children and their matched controls (total N = 210). A stepwise discriminant function analysis selected five nonreading measures from among 16 as the best diagnostic predictors of reading disability. These measures included WISC-R Information and Digit Span, self-reported family histories of reading problems, and tests of symbol-processing speed and letter fluency.

Adolescent

Functional asymmetry for facial affect perception in high and low hostile men and women.

The influence of cerebral asymmetry in the perception of affect on Type A behaviour was examined. Twenty-five men and 25 women classified as Type A or Type B, using the Framingham Type A Scale (FTAS) and the Cook-Medley Hostility Inventory (CMHO), participated. Subjects were required to identify the facial affect depicted in Ekman and Friesen's (1978) angry, happy, and neutral stimuli using a forced-choice reaction-time paradigm with only angry or happy alternatives signified by the respective response manipulanda. Stimuli were presented within the left or right visual fields tachistoscopically. The results showed faster affect perception by right hemisphere (LVF), hemispheric differences related to affective valence, and sex differences in affect asymmetry. Type A and Type B groups differed in the forced identification of neutral stimuli revealing affective bias but not processing speed differences on this perceptual task.

Adolescent

An electron microscopic study of the vascular factor in hemorrhagic diathesis.

Experimental diapedetic hemorrhage (oozing) was produced by streptokinase in rabbits and the fine structures of mesenterial microvessels were observed. Diapedesis of erythrocytes was seen in the venular side of microcirculation. On the contrary, no diapedesis was seen in true capillary on the arteriolar side. Sticking of erythrocytes to venular wall prior to diapedesis was proved, electron microscopically, to be the state in which red blood cells were trapped in the gaps on the endothelial junction. It was considered to be the morphological findings of the prediapedetic state. Erythrocytes passed through gaps on the endothelial junctions with high plasticities under any diapedetic conditions mentioned above. Furthermore, in author's experiments by ruthenium red staining, erythrocytes were observed just passing through the basement membrane under electron microscopy, in spite of its high speed process. It was found that the basement membrane is a very important barrier in erythrocyte diapedesis.

Animals