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Cognitive impairment and decline in different MS subtypes.

This paper presents results of two studies conducted to investigate cognition in different MS subtypes. First, the results of a study that has previously been published will be discussed. This was a cross-sectional study with 108 relapsing-remitting (RR), 71 secondary progressive (SP), 55 primary progressive (PP) MS patients, and 67 healthy controls [S.C.J. Huijbregts, N.F. Kalkers, L.M.J. de Sonneville, V. de Groot, I.E.W. Reuling, C.H. Polman, Differences in cognitive impairment of relapsing-remitting, secondary and primary progressive MS. Neurology 63 (2004) 335-339]. The second study involved a follow-up assessment after 2 years and included 30 SPMS patients, 25 PPMS patients, and 33 controls. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was used for all cognitive assessments. All patient groups demonstrated cognitive deficits compared to healthy controls. RRMS patients were less affected compared to patients with progressive MS subtypes on the Paced Auditory Serial Addition Task (PASAT) and the Symbol Digit Modalities Test (SDMT). These differences were attenuated after control for physical disability level as measured by the Expanded Disability Status Scale. RRMS and SPMS patients were more severely impaired than PPMS patients on the 10/36 Spatial Recall Task and Word List Generation. Results of the follow-up study indicated that both progressive MS subtypes showed a lack of improvement compared to controls on the PASAT and the SDMT, but not on the other tasks of the BRB-N, indicating that performance on tasks requiring multiple abilities concurrently, i.e. visuo-spatial ability and processing speed (SDMT) or working memory and processing speed (PASAT), is most likely to decline across time.

Auditory Perception↗

Performance discrepancies on the California Verbal Learning Test-Children's Version (CVLT-C) in children with traumatic brain injury.

One hundred sixty-seven children with traumatic brain injury (TBI), selected from an 8-year series of consecutive referrals to a Midwestern rehabilitation hospital, completed the California Verbal Learning Test-Children's Version (CVLT-C) and the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) within 1 year after injury. A large proactive interference (PI) effect, defined as performance on the second list that was at least 1.5 standard deviations below that on the 1st one, was statistically significantly more common in this clinical sample (21%) than in the CVLT-C standardization sample (11%). Other performance discrepancies, including retroactive interference, rapid forgetting, and retrieval problems, occurred at approximately the same rate in the clinical and standardization samples. Children with anterior cerebral lesions were about 3 times less likely to have a large PI effect than children without such lesions, but the former group performed worse on the first CVLT-C list. The impact of pediatric TBI on a wide range of CVLT-C quantitative variables was mediated by speed of information processing, as assessed by the WISC-III Processing Speed factor index. It is concluded that failure to release from PI is somewhat common, although certainly not universal, in children with TBI. Unlike with adults, anterior cerebral lesions are not associated selectively with an increased risk for PI after pediatric TBI but rather with a reduced efficiency of allocation of cognitive resources. Deficits in speed of information processing appear to be primarily responsible for the learning deficits on the CVLT-C after pediatric TBI.

Adolescent↗

The effects of stimulant drugs on information processing in elderly adults.

The effects of stimulant drug on information processing in elderly adults was studied. In Experiment 1, the effect of methylphenidate (MP) was examined in 8 young and 8 elderly women using a task (SERS) in which stimulus and response complexities were varied. MP speeded processing in the young but not in the elderly women. A second experiment was then conducted to isolate the age-stimulant effects. In Experiment 2, the effects of MP and 10 mg of d-amphetamine (DAMP) were studied in 12 young and 12 elderly men on different types of information processing. Stimulants changed performance on a continuous performance task in both groups. Both stimulants speeded processing on SERS in young, but not in elderly men. MP, however, speeded processing in both groups on a response processing task. The findings suggest that stimulants act on response processing and there appear to be several such processes. Some of these stages decline with age whereas others do not.

Adult↗

Speed of processing in normal aging: effects of speech rate, linguistic structure, and processing time.

Young and elderly adults heard three types of speech materials varying in both length and degree of semantic and syntactic constraints. Time compression was used to vary speech rates systematically to test a speed of processing hypothesis as one explanation of performance deficits associated with normal aging. In addition to segment length effects, the elderly participants showed significantly steeper rates of performance decline with increasing speech rate, with slope constants dependent on the structural constraints of the speech materials. The results are discussed in terms of processing rate hypotheses and context utilization.

Adolescent↗

A limit to the speed of processing in ultra-rapid visual categorization of novel natural scenes.

The processing required to decide whether a briefly flashed natural scene contains an animal can be achieved in 150 msec (Thorpe, Fize, & Marlot, 1996). Here we report that extensive training with a subset of photographs over a 3-week period failed to increase the speed of the processing underlying such Rapid Visual Categorizations: Completely novel scenes could be categorized just as fast as highly familiar ones. Such data imply that the visual system processes new stimuli at a speed and with a number of stages that cannot be compressed. This rapid processing mode was seen with a wide range of visual complex images, challenging the idea that short reaction times can only be seen with simple visual stimuli and implying that highly automatic feed-forward mechanisms underlie a far greater proportion of the sophisticated image analysis needed for everyday vision than is generally assumed.

Adult↗

Diagnostic utility of attention measures in postconcussion syndrome.

Neuropsychological evaluation may be of particular relevance in the detection of subtle cognitive impairments after mild traumatic brain injury (MTBI), including the subgroup of MTBI patients with a persistent postconcussion syndrome (PCS). Attention measures may be the most sensitive indicators of dysfunction associated with MTBI; however, previous studies have typically relied on the analysis of overall group differences, which may not reflect the diagnostic accuracy of attention measures when applied to individuals with MTBI. In the present study, subjects with persistent symptoms at least 3 months following a mild traumatic brain injury were compared with a sample of community living, normal control subjects in order to evaluate the sensitivity, specificity, and diagnostic accuracy of attention measures. Patients with PCS, screened with conservative inclusion and exclusion criteria, and a matched normal control group were administered six clinical tests of attention: Digit Span, Trail Making Test, Part A and Part B, Stroop Color-Word Test, Continuous Performance Test of Attention (CPTA), Paced Auditory Serial Addition Test (PASAT), and Ruff 2 & 7 Selective Attention Test. Consistent with prior research, these measures exhibited a wide range of sensitivity and specificity to possible cognitive impairment among patients. Attention measures may be the most sensitive indicators of dysfunction associated with PCS. Measures with high specificity (e.g., Stroop Color, and 2 & 7 Processing Speed) were shown to have strong positive predictive value, while measures with high sensitivity (e.g., CPTA) demonstrated strong negative predictive value for diagnosing PCS. Examination of the Odds Ratios indicated that measures assessing processing speed had a reliable, positive association with PCS, while measures without a processing speed component did not. Implications for making informed clinical decisions are discussed.

Acoustic Stimulation↗

High "intelligence," low "IQ"? Speed of processing and measured IQ in children with autism.

The uneven profile of performance on standard assessments of intelligence and the high incidence of savant skills have prompted interest in the nature of intelligence in autism. The present paper reports the first group study of speed of processing in children with autism (IQ 1 SD below average) using an inspection time task. The children with autism showed inspection times as fast as an age-matched group of young normally developing children (IQ 1 SD above average). They were also significantly faster than mentally handicapped children without autism of the same age, even when these groups were pairwise matched on Wechsler IQ. To the extent that IT tasks tap individual differences in basic processing efficiency, children with autism in this study appear to have preserved information processing capacity despite poor measured IQ. These findings have implications for the role of general and specific cognitive systems in knowledge and skill acquisition: far from showing that children with autism are unimpaired, we suggest that our data may demonstrate the vital role of social insight in the development of manifest "intelligence."

Adolescent↗

Does migraine headache affect cognitive function in the elderly? Report from the Maastricht Aging Study (MAAS).

The aim of this study was to examine two aspects of cognitive functioning-information processing speed and memory-in both young/middle-aged and older subjects with and without migraine, using data from a large population-based sample. We found that, although age had a large effect on processing speed and memory, migraine did not influence cognitive performance. In addition, there was no significant interaction between age and migraine on processing speed and memory. Our results suggest that, in the general population, migraine does not seriously affect cognitive functioning in young/middle-aged or older adults.

Adult↗

Long-term memory deficits in schizophrenia: primary or secondary dysfunction?

Long-term memory impairment is often found in schizophrenia. The question remains whether this is caused by other cognitive deficits. One hundred eighteen first-episode patients were compared with 45 control participants on several memory tasks. The role of processing speed and central executive functions on memory performance was examined with regression analysis for all participants and for patients separately. Deficits were found in general verbal learning performance and retrieval in episodic memory and semantic memory. Processing speed reduced disease-related variance in all memory variables. Coordination, organization of information, and speed of processing were the best predictors for long-term memory deficits in patients. The amount of explained variance, however, is small, especially in general verbal learning performance.

Adult↗

Determinants of Benton Facial Recognition Test performance in normal adults.

Clinical investigations have found that lesions of the right cerebral hemisphere can disrupt face perception. Much less is known about the determinants of facial discrimination in healthy adults, although age-related differences in many cognitive abilities have been shown to correlate with simple processing speed and variation in regional brain volumes. In this study, 174 healthy adults between the ages of 20 and 92 were asked to match pictures of unfamiliar faces. After their performance was regressed on age, sex, education, and perceptual comparison speed, adding terms for frontal lobe volume, nonfrontal volume, and ventricle-to-brain ratio (VBR) derived from magnetic resonance imaging improved the model and accounted for 35% of the variance in facial discrimination. VBR and processing speed alone accounted for nearly 34% of the variance. These findings suggest that both normal atrophic brain changes and decreases in processing speed contribute to individual differences in facial discrimination.

Adult↗

Speed of processing within semantic memory following severe closed head injury.

This study investigated the effects of severe closed head injury (CHI) on the speed of information processing within semantic categories. The question of whether subjects were able to benefit from priming was also investigated. Survivors of severe CHI who were less than 1 year postinjury and survivors who were greater than 1 year postinjury were compared with neurologically normal matched controls utilizing a category judgement task. The results demonstrated slower processing within semantic memory for both groups of CHI patients compared to normal controls. Furthermore, individuals with CHI were able to benefit from priming to the same relative degree as control subjects. Overall, the results suggested semantic organization remains intact after severe CHI, but accessing semantic information is slowed.

Adult↗

Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.

Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N = 41) from a randomized controlled trial who underwent ultra-high-field 7 T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.

Magnetic Resonance Imaging↗

Issues concerning relative speed of processing hypotheses, schizophrenic performance deficits, and prefrontal function: comment on Schooler et al. (1997)

The authors have found the data presented in the C. Schooler, E. Neumann, L. J. Caplan, and B. R. Roberts (1997) article to be interesting and of potential value in constraining the further development of detailed theoretical models of Stroop performance. However, the authors have found that the relative speed of processing account of stimulus onset asynchrony (SOA) effects given by Schooler et al. in Experiment 1 fails to address several important and vexing issues faced by such accounts, which have been highlighted by existing formal models. The authors also have expressed concerns about Schooler et al.'s, interpretation of the reduction in Stroop interference observed among individuals with schizophrenia in Experiment 2. Whereas the authors have acknowledged that it is plausible to relate this to a dysfunction of prefrontal cortex, they have pointed to equally plausible alternative explanations, which are not addressed by the experiment or in the discussion in the Schooler et al. article.

Attention↗

The effects of aging in the medial geniculate nucleus: a comparison with the inferior colliculus and auditory cortex.

A common problem among the elderly is a difficulty in discriminating speech. One factor that may contribute to this is deterioration in the ability to process the dynamic components of speech such as formant transitions. The frequency-modulated (FM) sweep is a useful stimulus for investigating the neural basis of temporal processing speed since it has features in common with formant transitions. Previously, we showed that when cells in the auditory cortex of aged animals were presented with FM sweeps, they exhibited a decrease in temporal processing speed when compared to cells recorded from young animals. However, this was not the case for cells in the inferior colliculus (IC) where neural responses did not appear to be affected by aging. One question that remains is how the auditory thalamus is affected by aging: Is it similar to that of the auditory cortex or of the IC. To this end, single units were recorded from the ventral division of the medial geniculate nucleus (MGNv) of young and aged anaesthetized rats in response to FM sweeps. Results showed that there were no age-related differences in speed or direction selectivity of FM sweep responses in the MGNv. When compared with units recorded from the IC and AI, the responses of MGNv neurons were similar to those of the IC. This suggests that temporal processing speed is affected by aging in the cortex, but not in the auditory thalamus or midbrain.

Acoustic Stimulation↗

Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia.

BACKGROUND: Neurocognitive deficits are recognized as a cardinal feature of schizophrenia, but the determinants of these deficits remain unknown. Recent reports have suggested that a functional polymorphism, Val(158)Met in exon III of the catechol-O-methyltransferase gene, shares approximately 4% variance with performance on the Wisconsin Card Sorting Test. These findings led to suggestions that the catechol-O-methyltransferase polymorphism may exert its effects by modulating prefrontal dopamine function, but few other neurocognitive measures have been examined, leaving open questions about phenotypic specificity. METHODS: We examined the effects of the catechol-O-methyltransferase Val(158)Met polymorphism in 58 individuals with chronic schizophrenia who completed a battery of 15 neurocognitive tests, which were reduced to four reliable neurocognitive domain scores. We examined the effects of genotype on these four domains and on global neurocognitive ability. RESULTS: The Met allele was associated with better performance in the Processing Speed and Attention domain, but not with other domain scores measuring executive and visuoperceptual functions, declarative verbal learning and memory, simple motor ability, or global neurocognitive function. Genotype shared approximately 11% of variance with Processing Speed and Attention scores, and approximately 2% of variance with Wisconsin Card Sorting Test scores. CONCLUSIONS: The findings provide independent support for the hypothesis that the catechol-O-methyltransferase Val(158)Met polymorphism influences neurocognitive function in schizophrenia, and suggest that the functional effects may be expressed on measures of Processing Speed and Attention. This information may prompt reconsideration of the "prefrontal dopamine" hypothesis and invites examination of a broader range of effects in efforts to refine the neurocognitive phenotype that is most relevant to variation in catechol-O-methyltransferase expression.

Adult↗

Aging, cognitive resources, and declarative learning.

A battery of cognitive tasks designed to assess information-processing speed, working memory capability, and declarative learning was administered to a cross-sectional sample of 477 adults ranging in age from 17 to 86 years. Results showed significant age-related decrements in all three constructs. A variety of structural equation models was fit to the results. The preferred model on empirical and conceptual grounds was one that showed (a) working memory capability as the most important mediator of age effects in declarative learning; (b) working memory capability as the mediator for the effects of general processing speed on declarative learning; and (c) differentiation among verbal, numeric, and spatial processing speed and between verbal and spatial working memory capability.

Adolescent↗

Age-related slowing of digit symbol substitution revisited: what do longitudinal age changes reflect?

A previous investigation reported that cross-sectional age differences in Digit Symbol Substitution (DSS) test performance reflect declines in perceptual processing speed. Support for the tenability of the processing speed hypothesis requires examining whether longitudinal age-related change in DSS performance is largely mediated by changes in speed. The present study used data from the Victoria Longitudinal Study to examine patterns and predictors of longitudinal change in DSS for 512 older adults (M(age) = 68.37 years, SD = 7.43). On the basis of multilevel modeling, baseline DSS performance was poorer for older participants and men, with longitudinal declines more pronounced with increasing age and decreasing speed. In contrast to the present cross-sectional findings, statistical control of change trajectories in perceptual speed using the same data did not substantially attenuate age changes. These discrepancies suggest different sources of variance may underlie cross-sectional age differences and longitudinal age changes for DSS.

Aged↗

WAIS-III and WMS-III performance in chronic Lyme disease.

There is controversy regarding the nature and degree of intellectual and memory deficits in chronic Lyme disease. In this study, 81 participants with rigorously diagnosed chronic Lyme disease were administered the newest revisions of the Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III), and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had poorer Full Scale and Performance IQ's. At the subtest level, differences were restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme disease participants performed more poorly on Auditory Immediate, Immediate, Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among WMS-III subtests, however, differences were restricted to Logical Memory (immediate and delayed) and Family Pictures (delayed only), a Visual Memory subtest. Discriminant analyses suggest deficits in chronic Lyme are best characterized as a combination of memory difficulty and diminished processing speed. Deficits were modest, between one-third and two-thirds of a standard deviation, consistent with earlier studies. Depression severity had a weak relationship to processing speed, but little other association to test performance. Deficits in chronic Lyme disease are consistent with a subtle neuropathological process affecting multiple performance tasks, although further work is needed to definitively rule out nonspecific illness effects.

Adult↗