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PubMed1992

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↗
PubMed1993

Effects of radiation therapy on adult brain behavior: evidence for a rebound phenomenon in a phase 1 trial.

Although radiotherapy (XRT) is a necessary course of treatment to prolong life expectancy in patients with many types of brain neoplasms, it has damaging effects that are little understood. We used a comprehensive neuropsychological battery to evaluate five patients with low-grade brain tumors prior to XRT and then at 3-month intervals up to 9 months postcompletion of XRT. We matched patients by age and education with six normal control subjects to assess baseline impairment. In intrasubject comparisons, we examined change over time postcompletion of XRT. In spite of varying locations of tumors, all patients showed deterioration in long-term memory at a mean of 1.5 months postcompletion of XRT. Patients also consistently demonstrated a rebound effect between means of 4.7 and 7.6 months post-XRT. We found no changes over time in working memory, attention, visuospatial processes, or on any other neuropsychological test with the exception of information-processing speed, which quickened over time. Functional measures of fatigue and mood did not correlate significantly with the long-term memory scores. Long-term memory appears sensitive to the proposed white matter changes thought to be the mechanism for the early-delayed effects of XRT. Our findings suggest a neurobehavioral model for studying the effects of XRT on brain functioning.

Adult↗
PubMed1994

Clinical characteristics in a kindred with early-onset Alzheimer's disease and their linkage to a G-->T change at position 2149 of the amyloid precursor protein gene.

Patients from five generations of a family developed presenile Alzheimer's disease (AD) early in the fifth decade. Recent memory, information-processing speed, sequential tracking, and conceptual reasoning were the earliest cognitive functions affected. Language and visuoperceptual skills were largely spared early in the course of the disease. Later, there were progressive cognitive deficits and inability to perform the activities of daily living. Death occurred, on average, 6 years after onset. Three autopsies in affected members revealed cerebral amyloid deposits and neurofibrillary tangles. Clinical and pathologic features were typical for familial AD. Direct DNA sequencing revealed a G-->T change at position 2149 of the amyloid precursor protein (APP) gene that resulted in the substitution of phenylalanine for valine in the transmembrane domain of the mature protein. This mutation was present in DNA from all four examined affected individuals and linked to the disease with a lod score of 3.25, and was the most probable cause of AD in this family.

Adult↗
PubMed2000

Visual attention impairments in Alzheimer's disease.

BACKGROUND: Impaired attention can hinder information processing at multiple levels and may explain aspects of functional decline in aging and dementia. Impairments of attention in early AD may contribute to performance reductions in other cognitive domains, including memory and executive functions. METHOD: - The authors analyzed the scores on a battery of tests of attention and cognitive abilities in 64 older individuals: 42 with mild AD and 22 control subjects without dementia. The authors tested the hypotheses that patients with AD would have impairments of visual attention, and that these impairments would correlate with dysfunction in other key cognitive domains. RESULTS: Patients with AD performed significantly worse than control subjects on measures of sustained attention, divided attention, selective attention, and visual processing speed. The differences were not due to differences in age, education, or basic visual function. Strong relationships were identified between reduced attention skills and overall cognitive impairment. CONCLUSIONS: Deterioration of attention abilities occurs in early stages of AD, and likely contributes to functional decline in these patients. More routine assessment of visual attention deficits could give a more accurate measure of functionally useful perception in patients with AD who show normal visual acuity and visual fields, perhaps providing useful clues to diagnosis and staging.

Aged↗
PubMed2002

Intracranial capacity and brain volumes are associated with cognition in healthy elderly men.

BACKGROUND: Brain size and intracranial capacity are correlated with cognitive performance in young healthy adults, but data are lacking on these relationships in older healthy adults. OBJECTIVE: To test the hypotheses that intracranial capacity, volumes of specific brain regions, and a measure of the shared variance between brain regions are positively associated with cognitive function in a sample of healthy, unmedicated elderly men (n = 97; mean age 67.8, SD 1.3). METHODS: Individuals underwent MRI, with measurements of intracranial area and volumetric measurements of hippocampi, temporal lobes, and frontal lobes. Cognitive testing included measures of premorbid intelligence, fluid intelligence, verbal memory, visuospatial memory, verbal fluency, and attention and processing speed. RESULTS: Cognitive tests showed significant positive intercorrelations throughout, and regional brain volumes were also universally, significantly, and positively intercorrelated. Intracranial area and several regional brain volumes correlated with tests of premorbid and fluid intelligence and tests of visuospatial memory. Tests of verbal memory and verbal fluency did not correlate significantly with brain volumes. Structural equation modeling demonstrated that the relationships between specific cognitive tests and regional brain volumes could best be summarized by a significant positive relationship between a general brain size factor and a general cognitive factor, and not by associations between individual tests and particular brain regions. CONCLUSIONS: In healthy elderly men, there are significant relationships between multiple cognitive tests and both intracranial capacity and regional brain volumes. These relationships may be largely due to longstanding associations between general cognitive ability and overall brain size.

Aged↗
PubMed2002

Does performance on theory of mind tasks decline in old age?

In the first reported study of theory of mind (ToM; the ability to attribute mental states) in old age, Happe, Winner, and Brownell (1998) observed better performance on ToM tasks in older participants (mean age 73 years) than in young participants (mean age 21 years). We present two experiments exploring the generality of this finding. Experiment 1 compared young, young-old, and old-old age groups (mean ages 19, 67, and 81 years, respectively) on their understanding of ToM stories both with and without the need to remember the information, and control studies that did not require the ability to attribute mental states. For ToM stories with a memory load, the young group performed significantly better than both the young-old and old-old groups; without a memory load, the young and young-old groups performed significantly better than the old-old group. In Experiment 2, young and old-old age groups (mean ages 21 and 81 years, respectively) were compared on their understanding of ToM and control stories without the need to remember the information. Again, the young group performed significantly better than the old-old group on ToM stories. There were no significant age differences in performance on the control stories in either experiment. The age deficit on ToM stories remained significant after taking account of measures of vocabulary and processing speed (Experiments 1 and 2), and measures of executive functioning (Experiment 2).

Adolescent↗
PubMed2004

Overgenerality of autobiographical memory in Alzheimer's disease.

OBJECTIVES: Overgenerality of autobiographical memory (ABM) is well documented in a range of clinical conditions, particularly in depressed and parasuicidal patients (e.g., Williams, 1996; Williams & Broadbent, 1986). This study extended the investigation to Alzheimer's disease (AD), and attempted to identify whether ABM overgenerality in the AD group is specifically expressed through an excess of categoric memories. DESIGN: AD sufferers and control participants were compared on their ABM specificity in a cued-recall task. METHOD: Ten AD patients and 10 controls, matched for age, gender and educational level, were administered an ABM specificity measure following their mental status assessment. A battery of neuropsychological tests provided an independent estimate of cognitive deficit severity in the following areas: long-term memory, IQ, working memory, processing speed, and verbal fluency. A control for depression was also employed. RESULTS: Compared to control participants, AD participants produced significantly fewer specific autobiographical memories. Additionally, the number of produced categoric overgeneral memories was significantly greater in the AD group in comparison with the controls. CONCLUSION: This study demonstrates the existence of ABM overgenerality in AD, manifested through an excess of categoric memories. Consistent with the mnemonic interlock theory (Williams, 1996), AD sufferers seem to lack cognitive resources to conduct a directed search for a specific memory, and stop at the categoric descriptions stage. This may contribute to lack of specificity in ABM retrieval.

Aged↗
PubMed1995

Validity of the WISC-III for deaf and hard of hearing persons.

The relationships of the WISC-III Performance scale with the WISC-R Performance scale and the WRAT-R subscales were investigated for a sample of 47 students who are deaf and hard of hearing. Over a three year time period, the relationships between the WISC-III and WISC-R Performance IQs was high, r(43) = +.93. As anticipated, the WISC-III and WISC-R Performance IQ. A Varimax rotation revealed the presence of two factors, Perceptual Organization and Processing Speed, which accounted for 76.5% of the variance in the WISC-III performance IQ. Of the six WISC-III Performance subtests, only Coding did not contribute to the Performance IQ. Students who communicated via Total Communication (M = 92.5) exhibited higher Performance IQ means than did students who communicated orally (M = 82.6). The WISC-III Performance IQ was moderately related to the WRAT-R subscales, having the strongest association with the Arithmetic subscale. Implications of these findings for practitioners are discussed.

Achievement↗
PubMed2002

Sensing wave-front amplitude and phase with phase diversity.

We show in benchtop experiments that wave-front phase estimation by phase diversity can be significantly improved by simultaneous amplitude estimation. Processing speed, which will be important for real-time wave-front control applications, can be enhanced by use of small-format detectors with pixels that do not fully sample the diffraction limit. Using an object-independent phase-diversity algorithm, we show that, for both pointlike and extended objects, the fidelity of the phase and amplitude estimates degrades gracefully, rather than catastrophically, as the sampling becomes coarser. We show in simulation that the same algorithm also improves the fidelity of image reconstruction of complex targets.

Journal Article↗
PubMed2007

Multilevel quality-guided phase unwrapping algorithm for real-time three-dimensional shape reconstruction.

A multilevel quality-guided phase unwrapping algorithm for real-time 3D shape measurement is presented. The quality map is generated from the gradient of the phase map. Multilevel thresholds are used to unwrap the phase level by level. Within the data points in each level, a fast scan-line algorithm is employed. The processing time of this algorithm is approximately 18.3 ms for an image size of 640x480 pixels in an ordinary computer. We demonstrate that this algorithm can be implemented into our real-time 3D shape measurement system for real-time 3D reconstruction. Experiments show that this algorithm improves the previous scan-line phase unwrapping algorithm significantly although it reduces its processing speed slightly.

Journal Article↗
PubMed1993

Equivalent luminance contrast of red-green drifting stimuli: dependency on luminance-color interactions and on the psychophysical task.

The equivalent luminance contrast (EqLC) of red-green drifting stimuli was assessed by three independent methods. The first method [method (a)] consisted in adjusting the luminance contrast of a yellow, equichromatic stimulus to match the direction-discrimination performances that were obtained with a red-green, equiluminant stimulus. The second method [method (b)] was a replica of the standard motion-cancellation technique proposed by Cavanagh et al. [J. Opt. Soc. Am. A 1, 894 (1984)]. The third method [method (c)] consisted in adjusting the luminance contrast of the same yellow, equichromatic stimulus as in method (a) to match the perceived speed of the red-green, equiluminant stimulus. The three estimated EqLC's are all different. It is argued that differences between EqLC's assessed by means of methods (a) and (b) result from unbalanced interactions between the chromatic and achromatic, directional-sensitive mechanisms and that differences between EqLC's assessed by means of methods (a) and (c) reveal unequal transfer efficiencies from the directional to the speed-processing stages in the chromatic and achromatic pathways.

Color↗
PubMed2004

Analysis of low-coherence interference fringes by the Kalman filtering method.

Interferometers with low-coherence illumination allow noncontact measurement of rough-surface relief with a wide range of measurement definition by locating the visibility maxima of interference fringes. The problem is light scattering by the surface to be measured, which can cause distortion of low-coherence interferometric signals. We propose to use a stochastic fringe model and a Kalman filtering method for processing noisy low-coherence fringes dynamically. Prediction of the fringe's signal value at each discretization step is based on all the information available before this step; the prediction error is used for dynamic correction of the estimates of the fringe envelope and phase. The advantages of the Kalman filtering method consist in its immunity to noise, optimal fringe evaluation, and data-processing speed.

Journal Article↗
PubMed2006

Foveal visual strategy during self-motion is independent of spatial attention.

Translational self-motion disturbs the stability of retinal images by inducing a pattern of retinal optic flow that cannot be compensated globally by a single eye movement. The eyes must rotate by different amounts, depending on which spatial location needs to be stabilized on the retina. However, compensatory eye movements during steady fixation are always such as to maintain visual acuity on the fovea at the expense of significant image slip on the peripheral retina. We investigated whether such a foveal visual strategy during translation is hard-wired or whether it embeds enough flexibility to also allow for behaviorally relevant objects outside the foveae to be stabilized preferentially on the retinas. Monkeys were moved forward or backward and leftward or rightward passively in darkness while planning a saccade or bar release to peripheral dimmed targets. By comparing the eye movements made during these tasks with those under conditions of steady fixation, we found that the motion-induced eye movements depended only on current fixation. This was true even during the last milliseconds just before a saccade to the peripheral target. We conclude that the foveal stabilization strategy is invariant and solely dependent on current eye position, a strategy that is optimal for both processing speed and efficiency in the extraction of heading information from retinal flow during self-motion.

Adaptation, Physiological↗
PubMed2002

Validity of maternal report of prenatal alcohol, cocaine, and smoking in relation to neurobehavioral outcome.

OBJECTIVE: Evidence that mothers report higher levels of drinking retrospectively than during pregnancy has led some investigators to suggest that women systematically underreport alcohol antenatally and that alcohol-related deficits may actually reflect heavier prenatal exposure. This study is the first to compare the validity of antenatal and retrospective reports of pregnancy drinking, drug use, and smoking in relation to effects on infant neurobehavioral outcomes. METHODOLOGY: Three hundred fifty-four inner-city mothers were interviewed regarding their alcohol, drug use, and smoking during pregnancy and retrospectively at 13 months' postpartum. Their infants were assessed at 6.5, 12, and 13 months on a large battery of neurobehavioral assessments. RESULTS: Although higher levels of alcohol were reported retrospectively, the correlations of prenatal alcohol exposure with infant outcome were as strong or stronger for the antenatal measures and only the antenatal reports predicted poorer cognitive performance on the Bayley Scales and symbolic play, slower processing speed on the Fagan Test of Infant Intelligence and cross-modal transfer, and slower infant reaction time. Women also reported higher levels of cocaine and marijuana but not cigarette smoking retrospectively. Relations between cocaine use and smoking on birth size and gestational age were as strong for either report. No effects were detected in relation to either report of marijuana use during pregnancy. CONCLUSIONS: These findings suggest that antenatal alcohol interviews provide the most valid information and demonstrate the importance of assessing prenatal alcohol use during pregnancy to minimize the risk of failing to detect neurobehavioral deficits. Adverse effects were consistently seen at levels as low as 0.5 oz absolute alcohol/day (the equivalent of 7 drinks per week) based on maternal antenatal report. These data suggest that alcohol-related deficits do not reflect heavier prenatal exposure than that reported during pregnancy and that threshold values derived from antenatal reports are reasonably accurate.

Adult↗
PubMed2005

Functional plasticity or vulnerability after early brain injury?

CONTEXT: Traumatic brain injury (TBI) is a common, acquired, childhood disability that may be used as a model to understand more completely the impact of early brain injury on both brain structure and day-to-day function. Contrary to previously held views of the "plasticity" of the young brain, recent research suggests that such early insults may have a profound impact on development. To date, these suggestions remain largely untested. OBJECTIVES: To plot changes in cognitive abilities after childhood TBI over the 30 months after injury and to examine the impact of age at injury on cognitive outcomes. DESIGN: Prospective longitudinal study. SETTING: Royal Children's Hospital, Victoria, Australia. MAIN OUTCOME MEASURES: Global intellectual ability, verbal and nonverbal skills, attention, and processing speed. PARTICIPANTS: A total of 122 children admitted to the hospital with a diagnosis of TBI were divided according to injury age, ie, young (age: 3-7 years) or old (age: 8-12 years), and injury severity (mild, moderate, or severe) and were evaluated acutely and at 12 and 30 months after injury. An additional sample of children injured before 3 years of age (n = 27) was compared with these groups with respect to global intellectual ability only. RESULTS: A clear relationship was documented between injury severity and cognitive performance. For children who sustained severe injury, younger age at injury was associated with minimal, if any, recovery after injury, but better outcomes were observed after severe TBI among older children. Age at injury was not predictive of outcomes for children with mild or moderate TBI, although infants (age: 0-2.11 years) with moderate TBI showed poorer outcomes than did older children with injury of similar severity. CONCLUSIONS: Findings support a "double-hazard" model for severe and early brain insults and add to the ongoing debate regarding cerebral plasticity, suggesting that, contrary to traditional views, young children who sustain severe TBI in early childhood or moderate or severe TBI in infancy may be particularly vulnerable to significant residual cognitive impairment. From a clinical perspective, results indicate that long-term follow-up monitoring and management should be targeted to this high-risk group.

Brain Injuries↗
PubMed2006

Surgically restoring portal blood flow to the liver in children with primary extrahepatic portal vein thrombosis improves fluid neurocognitive ability.

OBJECTIVES: Children with primary extrahepatic portal vein thrombosis (EHPVT) have portal-systemic shunting, which may lead to disturbed neurocognitive function similar to portal-systemic encephalopathy (PSE) seen with chronic liver disease and cirrhosis. The functions most affected are those involving fluid cognitive ability, which comprise neurocognitive domains such as attention, processing speed, and short-term memory, that are particularly vulnerable to systemic illness or diffuse neurologic insult. We determined the fluid cognitive ability of children with EHPVT and whether surgically restoring portal blood flow by mesenteric left portal vein bypass (MLPVB) improved it. DESIGN: Twelve children with EHPVT and no overt PSE underwent comprehensive neurocognitive testing before and 1 year after undergoing surgery with intent to perform MLPVB. The evaluations sampled 4 functional domains at both time points: (1) neurobehavioral (behavior, emotional, executive functioning); (2) broad cognitive (intelligence, achievement); (3) fluid ability (attention, mental speed, working memory, memory encoding); and (4) visual motor (drawing, fine motor). Tasks in the fluid-ability and visual-motor domains were expected to be especially sensitive to adverse effects of EHPVT and to be most likely to show improvement with MLPVB. The test group consisted of 8 subjects who underwent successful MLPVB, and the comparison group was composed of 3 patients who received distal splenorenal shunts and one whose MLPVB failed. RESULTS: Both groups demonstrated similar fluid cognitive ability at initial evaluation. Successful MLPVB resulted in significantly improved fluid cognitive function: in the fluid cognitive domain, significant improvements were seen for the hit reaction time variability in the Conner's Continuous Performance Test, the attention scale of the Cognitive Assessment System, and immediate verbal memory in the Children's Memory Scale. In the visual-motor domain, z scores on the Grooved Pegboard Test improved. No improvement was observed in the comparison group. DISCUSSION: The results show that surgically restoring portal flow to the liver in children with primary EHPVT results in improved fluid cognitive ability. Subjects showed some neurocognitive abnormalities involving mainly fluid cognitive ability consistent with minimal PSE seen in adults with chronic liver disease. Cognitive defects in patients with minimal PSE seem to relate primarily to attention and fine motor skill, and although affected patients can function in everyday life, they are at risk for performance deficits in educational and vocational situations requiring the ability to pay close attention and react quickly (eg, driving, employment in manufacturing). The tests we administered in these domains are pediatric equivalents to measures used to detect minimal PSE in adults and should detect abnormalities in the same functional domains. Our results suggest that a narrow battery of tests could be used to detect minimal PSE in children in a manner similar to the 5-test battery used in adults, eliminating the need for the comprehensive and broad testing we performed. Our findings suggest that shunting of portal blood from the liver in primary EHPVT can result in PSE and question whether it is as benign a disease as previously thought. The importance of our findings is twofold. For understanding the pathophysiology of PSE, we have shown that restoring blood flow to the liver improves cognitive function in children with EHPVT. For therapy for EHPVT, it becomes clear that MLPVB is an excellent treatment option. It is effective for treating the complications of portal hypertension and provides effective portal blood flow that other medical and surgical therapies do not. The findings provide additional evidence that primary EHPVT should be considered curable by MLPVB. However, comparison of overall risks and benefits of MLPVB with those of other therapeutic options and longer-term outcome studies must be completed before MLPVB can be fully endorsed as the best treatment for EHPVT in children. CONCLUSIONS: Surgical restoration of portal venous flow to the liver in children with primary EHPVT by MLPVB improves fluid cognitive ability. MLPVB should be considered in treating primary EHPVT, because it corrects portal blood flow and could optimize learning potential.

Anastomosis, Surgical↗
PubMed2002

A combined electrophysiological and behavioural study for the assessment of activity-dependent changes in mice.

Activity-dependent adaptive changes in the nervous system involve structural and functional changes in the cortical circuitry. In this work the cortical function was studied by repeated recording of the somatosensory and motor potentials evoked by whisker deflections after altered sensory-motor experience in adult mice. The latencies of motor and somatosensory evoked potentials were found to shorten, while their amplitudes decreased, after a behavioural challenge involving the vibrissal apparatus. Sensory deprivation achieved by whisker trimming resulted in a partial reversal of the changes observed after increased activity. The derived parameters imply that cortical information processing speeds up as a result of experience, while decreased activity has the opposite effect. The methods used throughout the experiment were minimally invasive, and thus proved to be sufficient for the long-term follow-up of cortical functions.

Animals↗