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Neuropsychological profiles of adults with Klinefelter syndrome.

Children and adolescents with Klinefelter syndrome (XXY) have been reported to show deficits in language processing including VIQ < PIQ and a learning disability in reading and spelling. However, whether this is characteristic of adults with Klinefelter syndrome has not been established. Thirty-five men with Klinefelter syndrome, aged 16 to 61, and 22 controls were evaluated with a comprehensive neuropsychological battery. The Klinefelter patients scored significantly below controls in language skills, verbal processing speed, verbal and nonverbal executive abilities, and motor dexterity. Within the Klinefelter sample, three cognitive subgroups were identified: VIQ 7 or more points below PIQ (n = 10), VIQ within 6 points of PIQ (n = 12), and PIQ 7 or more points below VIQ (n = 12). The deficits detected in language, verbal processing speed, and verbal executive skills were found to be isolated to the VIQ < PIQ subgroup, while the abnormalities in motor dexterity and nonverbal executive skills were confined to the PIQ < VIQ subgroup. Older age was significantly correlated with increases in VIQ relative to PIQ in the patient group, which suggests the intriguing possibility that the PIQ < VIQ subgroup primarily emerges in young adulthood, perhaps in response to the reported hormonal abnormalities detected in Klinefelter syndrome patients during puberty.

Adolescent↗

Word finding difficulty as a post-polio sequelae.

OBJECTIVE: Seventy-nine percent of respondents to the 1990 National Post-Polio Survey reported difficulty "thinking of words I want to say," with 37% reporting frequent, moderate-to-severe word finding difficulty. This study was undertaken to objectively document polio survivors' word finding difficulty and to identify its relationship to fatigue, neuropsychologic processes requiring cortical activation, and a peripheral marker for brain dopamine secretion. DESIGN: In this study, 33 polio survivors were administered the Post-Polio Fatigue Questionnaire, Animal Naming and FAS Tests, and tests of attention and information processing speed. Plasma prolactin was also measured as a marker for brain dopamine secretion. RESULTS: Subjects reporting high fatigue severity and word finding difficulty had clinically abnormal or significantly lower Animal Naming Test scores compared with subjects with low symptom severity. Impaired performance on the most difficult tests of attention and information processing speed were also associated with lower scores on the word finding tests. A significant negative correlation between Animal Naming Test scores and plasma prolactin suggests that a decrement in brain dopamine secretion is related to reduced animal naming ability. CONCLUSIONS: These data support the hypothesis that decreased dopamine secretion, possibly secondary to poliovirus damage to the basal ganglia, may underlie not only fatigue and impaired attention but also word finding difficulty in polio survivors.

Anomia↗

Sensory and cognitive factors influencing functional ability in older adults.

BACKGROUND: Age-related sensory and cognitive impairments have been related to functional performance in older adults. With regard to cognitive abilities, processing speed in particular may be strongly related to older adults' abilities to perform everyday tasks. Identifying and comparing cognitive correlates of functional performance is particularly important in order to design interventions to promote independence and prevent functional disability. OBJECTIVE: The present study examined the relative importance of cognitive (specifically, speeded and nonspeeded) and sensory factors in relation to older adults' functional abilities. Functional abilities included measures of mobility and performance of everyday activities. METHODS: A cross-sectional study design was employed. Five hundred and thirty adults between the ages of 62 and 94 completed measures of sensory, cognitive (including processing speed, attention, memory, intelligence) and functional abilities. RESULTS: Overall, functional performance was most strongly associated with cognitive speed performance, but nonspeeded cognitive and sensory abilities also accounted for significant amounts of variance in functional performance. Age explained a small but statistically significant amount of additional variance in some functional abilities, but no additional variance in self-reported mobility measures. CONCLUSION: These findings point to the potential impact of multifaceted training programs, targeting both sensory and cognitive abilities for maintaining functional abilities.

Activities of Daily Living↗

Reaction time measures of sustained attention differentiate bipolar disorder from schizophrenia.

Although continuous performance tasks (CPTs) are becoming more common in psychiatric research, it remains unclear which performance measures best differentiate psychiatric patient groups and along which psychological dimensions. To address this the authors examined sustained attention decrements in patients with bipolar disorder and schizophrenia using CPT measures of perceptual sensitivity, response bias, and psychomotor processing speed. Patients with bipolar disorder with psychotic features (N=20), schizophrenia (N=20), and healthy controls (N=20) were evaluated using structured clinical interviews. These patients were rated with the Scale for the Assessment of Positive Symptoms and the Young Mania Rating Scale before completing a degraded-stimulus version of the CPT. Psychomotor processing speed was the only measure that reliably differentiated the groups across the entire vigilance period and was the strongest predictor of group membership. These findings suggest that reaction time measures may be sensitive to differences in the sustained attention abilities of patients with bipolar disorder and schizophrenia. By incorporating reaction time measures into CPT assessments, discriminant ability may be enhanced.

Adult↗

Specificity of neurobehavioral outcomes associated with prenatal alcohol exposure.

A current issue in alcohol research is whether a "neurobehavioral profile" can be identified for prenatal alcohol exposure, even when dysmorphic features are not present, or whether comparable neurobehavioral deficits are detected when damage is incurred by numerous neurotoxicants to which the fetus is exposed during a common developmental period. Failure to detect such differences may, in part, be an artifact of the global developmental tests used to assess outcome. Cognitive effects of prenatal exposure to three different teratogens [polychlorinated biphenyls (PCBs), alcohol, and cocaine] are examined to determine whether exposure to each substance results in a common or different pattern of impairment on the same set of newer, more narrow band infant tests. Comparison of findings from three independent cohorts indicate that PCB exposure was related to poorer recognition memory on the Fagan Test of Infant Intelligence (FTII) in Michigan infants exposed prenatally to PCB-contaminated fish, whereas prenatal alcohol exposure was unrelated to recognition memory but to slower processing speed on a new FTII measure and slower reaction time on Haith's Visual Expectancy Paradigm (VExP) in our Detroit alcohol-exposed infants. Preliminary findings from a new study of infants recently born to Taiwanese women accidentally contaminated with sizable amounts of PCBs indicate recognition memory deficits, confirming our Michigan findings, but no processing speed effects on the FTII. Recent findings from our Detroit cohort suggest that heavy prenatal cocaine exposure is related to poorer recognition memory on the FTII, but faster reaction times on the VExP, a pattern different from that seen for either PCBs or alcohol.

Brain Damage, Chronic↗

Executive functioning and speed of processing in phenylketonuria.

Treated phenylketonuria (PKU) has been linked to dopaminergic depletion in the dorsolateral prefrontal cortex, potentially leading to selective executive impairment. White matter abnormalities may lead to generalized slowing of information processing. These 2 hypotheses were evaluated in adults with PKU on a lifelong diet. Those with PKU were significantly slower than the control group regardless of working memory load on an n-back task and marginally slower regardless of trial type (inhibitory or noninhibitory) on a flanker task. There were no significant differences in speed on object alternation learning or perceptual judgment tasks. There were no group differences in accuracy on any task. These findings do not appear consistent with the selective executive hypothesis. A cognitive slowing account may prove more informative in adults with PKU, but more evidence is needed. The findings suggest that continuous dietary management is a fairly successful strategy in terms of cognitive outcome for adults.

Adolescent↗

Construct overlap in resource theories of memory aging. Commentary.

This article evaluates the conceptual status of working memory, processing speed, executive function and sensory function as mediational constructs to explain memory aging. The main difficulty for these mediational constructs is that they may not be independent. Mediational constructs may overlap with each other or with the dependent variable due to theoretical, substantive or methodological reasons. It is argued that sensory function has an advantage over processing speed, working memory and executive function as a mediational construct because it is non-cognitive. The problem of construct overlap is relevant to both cross-sectional and longitudinal studies. Further research is required to evaluate the relative importance of mediational constructs in theories of memory aging, general intellectual aging and dementia.

Aging↗

The effect of practice on the visual detection of near-threshold lines.

Two observers practised to detect small target lines of varying luminance presented either within a context of collinear inducing stimuli, or without the context in separate blocks. A two-alternative spatial-forced-choice procedure using the method of constant stimuli was employed. For blocks of 500 trials, reflecting individual performance on five successive days of training, the percentage of correct responses, and the response times were analyzed. After several thousands of trials, i.e. several weeks of practice, both observers managed to detect targets presented at their strongest luminance within the context condition. Without the context, these targets remained undetected. Response times (RT) vary nonsystematically during training. Once detection is observed at the highest target luminance, the accuracy of the individual responses (percentage of correct responses) systematically increases, and processing speed (RT) systematically decreases with increasing target intensity. These results show that, within the appropriate perceptual context, practice can lead to a better detectability of visual stimuli presented at luminance levels near detection threshold. This improvement is reflected by an optimization of the visual integration of the different luminance levels of the target (sensory coding), and processing speed (response routine) during training.

Adult↗

Mild hearing impairment can reduce verbal memory performance in a healthy adult population.

We studied to what extent immediate and delayed recall in an auditory verbal learning paradigm was affected by basic information processing speed (digit copying) and hearing acuity (average hearing acuity at 1, 2 and 4 KHz at the better ear). A group of 453 individuals in the age between 23 and 82 years with no overt hearing pathology was recruited from a larger study of cognitive aging (Maastricht Aging Study, MAAS). After controlling for age, sex, educational level, and processing speed it was found that a mild to moderate hearing loss predicted lower verbal memory performance. Auditory administered verbal memory tests can underestimate true memory performance, particularly in older individuals with unknown hearing status.

Adult↗

Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis.

BACKGROUND: The relationship of gray and white matter atrophy in multiple sclerosis (MS) to neuropsychological and neuropsychiatric impairment has not been examined. METHODS: In 40 patients with MS and 15 age-/sex-matched normal controls, the authors used SPM99 to obtain whole brain normalized volumes of gray and white matter, as well as measured conventional lesion burden (total T1 hypointense and FLAIR hyperintense lesion volume). The whole brain segmentation was corrected for misclassification related to MS brain lesions. To compare the effects of gray matter, white matter, and lesion volumes with respect to brain-behavior relationships, the MS group (disease duration = 11.2 +/- 8.8 years; EDSS score = 3.3 +/- 1.9) underwent neuropsychological assessment, and was compared to a separate, larger group of age-/sex-matched normal controls (n = 83). RESULTS: The MS group had smaller gray (p = 0.009) and white matter volume (p = 0.018), impaired cognitive performance (verbal memory, visual memory, processing speed, and working memory) (all p < 0.0001), and greater neuropsychiatric symptoms (depression, p < 0.0001; dysphoria, p < 0.0001; irritability, p < 0.0001; anxiety, p < 0.0001; euphoria, p = 0.006; agitation, p = 0.02; apathy, p = 0.02; and disinhibition, p = 0.11) vs controls. Hierarchical stepwise regression analysis revealed that whole gray and white matter volumes accounted for greater variance than lesion burden in explaining cognitive performance and neuropsychiatric symptoms. White matter volume was the best predictor of mental processing speed and working memory, whereas gray matter volume predicted verbal memory, euphoria, and disinhibition. CONCLUSION: Both gray and white brain matter atrophy contribute to neuropsychological deficits in multiple sclerosis.

Atrophy↗

The development of visuo-spatial working memory.

Children's performance on tests of visuo-spatial working memory improves with age, although relatively little is known about why this happens. One explanation concerns the development of the ability to recode visually presented information into phonological form. This process appears to be used from around 8 years of age and is a major contributor to tasks in which stimuli can be verbally labelled. However, evidence suggests that phonological recoding cannot account for all of the age-related change in performance on visuo-spatial working memory tasks. In this review, four other mechanisms (knowledge, processing strategies, processing speed, and attentional capacity) are considered in terms of their contribution to children's visuo-spatial working memory development.

Child↗

Cognitive abilities in reading-disabled children: a longitudinal study.

Longitudinal psychometric test data collected at two different ages (9.4 +/- 1.3 and 14.8 +/- 1.2 years) were utilized to compare the developmental rates of 69 pairs of reading-disabled and matched control children. Results of a two-factor (GROUP X TIME), mixed-model, multivariate analysis of variance indicated that reading-disabled children manifested deficits on measures of academic achievement, symbolic processing speed and spatial reasoning abilities at both ages. Although both reading-disabled and control children were found to improve significantly between the two testing sessions, the lack of a significant GROUP X TIME interaction on measures of academic achievement and spatial reasoning abilities indicated that the rate of development was similar for the two groups. For measures of symbolic processing speed, however, differences between reading-disabled and control children were somewhat greater at the later age.

Achievement↗

Correlations of functional capacity and neuropsychological performance in older patients with schizophrenia: evidence for specificity of relationships?

BACKGROUND: Neuropsychological (NP) performance is a consistent correlate of everyday functioning in schizophrenia, but it is unclear whether relationships between individual NP ability areas and domains of everyday functioning are general or specific. Assessments of real-world everyday functioning may be influenced by environmental and social factors (e.g., social security, disability status, opportunities and restrictions in living situations). This study examined the specificity of the relationships between different NP abilities and performance-based measures of social and living skills. METHODS: 181 ambulatory older (age>50) patients with schizophrenia were examined with NP tests measuring episodic and working memory, executive functioning, verbal fluency, and processing speed. All subjects performed tasks examining social (Social Skills Performance Assessment: SSPA) and everyday living (UCSD Performance Based Skills Assessment: UPSA) skills. RESULTS: Using canonical analysis, the NP variables were used to predict the functional capacity measures. The analysis found that 37% of the variance in the functional capacity and NP measures was shared, X(2) (54)=106.29, p<.001. Two canonical roots described the cognitive variables and the roots were differentially associated with everyday living and social skills. The root loading on processing speed, episodic memory, and executive functions were associated with UPSA scores, while the root loading on working and episodic memory and verbal fluency were associated most strongly with social competence. IMPLICATIONS: Social and everyday living skills deficits in patients with schizophrenia may reflect generally independent domains of functional outcome, linked through cognitive performance. The data suggest that somewhat different cognitive processes are associated with these two domains of functional capacity, although there appears to be some overlap, which may be due to the nature of the NP tests employed.

Activities of Daily Living↗

Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer's disease.

BACKGROUND: Early diagnosis of dementia is important for those who might benefit from treatment. We designed a brief comprehensive neuropsychological test battery to help differentiate control subjects from patients with mild cognitive impairment (MCI) and dementia. METHOD: The battery included tests of memory, attention, executive function, speed, perception and visuospatial skills. It was administered to subjects from the OPTIMA cohort: 51 controls, 29 with MCI, 60 with 'possible' or 'probable' Alzheimer's disease (AD) (NINCDS/ADRDA) and 12 with cerebrovascular disease (CVD). Mann-Whitney U tests were used to compare performance of controls with other diagnostic groups. The sensitivity and specificity of the tests were determined using Receiver Operating Characteristic curve analyses. The effects of age, gender and years of education on test performance were determined with Spearman's rank correlations. RESULTS: The AD group performed worse than controls on all tests except an attention task. The Hopkins Verbal Learning Test and The Placing Test for episodic memory showed significant discriminative capacity between controls and other groups. Attention and processing speed tests discriminated CVD from controls. Category fluency, episodic memory tests and the CLOX test for executive function distinguished MCI from AD. Spearman's correlations showed negative associations between age and processing speed. Years of education affected performance on all tests, except The Placing Test. CONCLUSIONS: Certain neuropsychological tests have been shown to be sensitive and specific in the differential diagnosis of various types of dementia and may prove to be useful for detection of MCI.

Aged↗

Brain metabolites and cognitive function among older depressed and healthy individuals using 2D MR spectroscopy.

Brain metabolites of choline (Ch) and myo-Inisotol (mI) have been reported as elevated among geriatric depressed patients. Two-dimensional (2D) magnetic resonance spectroscopy (MRS) provides estimates of Ch, mI, and creatine (Cr) similar to one-dimensional MRS, and it also estimates the resonances of the Ch-containing compounds of phosphoethanolamine (Pe) and phosphocholine (PCh). In this cross-sectional geriatric study, 14 depressed patients and 14 healthy volunteers who were comparable in age, gender, education, comorbid medical burden, and Mini-Mental State Examination (MMSE) scores completed 2D MRS and a neurocognitive battery. A voxel in the left dorsolateral cortex, which was comprised of approximately 60% white matter, was used to estimate the CR ratios of Ch, PCh, Pe, and mI. Composite scores for cognitive function were developed for verbal learning, recall, recognition, executive function, hypothesis generation, and processing speed. Among nondepressed subjects, cognition was positively correlated with Ch/Cr and mI/Cr and negatively correlated with PCh/Cr in four domains of verbal learning, recognition, recall, and hypothesis generation. In contrast, depressed patients did not have consistent relationships between Ch/Cr, mI/Cr, and PCh/Cr and cognition. There was a significant difference in the overall pattern of associations between the four metabolites and verbal learning and processing speed in depressed patients compared to healthy controls. The attenuated relationship between metabolites and specific cognitive domains in patients with late-life MDD suggests that the level of cognitive performance observed during depressive episodes may be associated with changes in biochemistry within the frontostriatal neuronal circuitry.

Age Factors↗

Hypothermia-induced platelet aggregation and cognitive decline in coronary artery bypass surgery: a pilot study.

Hypothermia-induced platelet aggregation (HIPA) was previously reported in whole blood exposed to synthetic surfaces at 24 degrees-32 degrees C in one-third of normal subjects tested. Cardiopulmonary bypass, conducted with hypothermia, may lead to such aggregation, resulting in microvascular occlusion contributing to cognitive impairment. This pilot study was conducted to explore the relationship between HIPA and cognitive outcome at hospital discharge in patients undergoing coronary artery bypass graft (CABG) surgery as a first step toward a longer-term study. Patients (n = 45) undergoing mild to moderate hypothermia (32 degrees-28 degrees C) during CABG surgery underwent cognitive testing preoperatively and prior to hospital discharge. Tests included: visual and verbal memory, mental processing speed, executive function, language, and intellectual function. HIPA was identified using an in vitro assay in which blood flowing in polyvinychloride tubing was subjected to hypothermia, and platelet aggregates were detected using microscopy and passing the exiting blood through a 20-microm pore filter. Forty-four percent of patients exhibited HIPA. The entire cohort exhibited significant postoperative cognitive decline in verbal memory, mental processing speed and executive function. There was greater cognitive decline in the group with HIPA compared with the group not exhibiting this phenomenon. The patients with HIPA showed significant decline in four of five cognitive measures whereas patients not exhibiting this phenomenon declined in only two of five cognitive measures. HIPA appears to be associated with an added risk of cognitive decline immediately following CABG surgery employing mild to moderate hypothermia. The findings of our study suggest the long-term cognitive effects of hypothermia-induced platelet aggregation need to be explored.

Aged↗

One-year double-blind study of the neurocognitive efficacy of olanzapine, risperidone, and haloperidol in schizophrenia.

Neurocognitive deficits in schizophrenia can reach 1 to 2 standard deviations below healthy controls. The comparative effect of typical and atypical antipsychotic medications on neurocognition is controversial, and based primarily on studies with small samples and large doses of typical comparator medications. The present study assessed neurocognitive efficacy. It was hypothesized that olanzapine treatment would improve neurocognitive deficits to a greater degree than either risperidone or haloperidol treatment. This was a double-blind, randomized, controlled, parallel study with neurocognition assessed at baseline, and 8, 24, and 52 weeks. Per protocol, the haloperidol arm was discontinued. Four hundred and fourteen inpatients or outpatients with schizophrenia and schizoaffective disorder were treated with oral olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Individual domains (executive function, learning and memory, processing speed, attention/vigilance, verbal working memory, verbal fluency, motor function, and visuospatial ability) were transformed into composite scores and compared between treatment groups. At the 52-week endpoint, neurocognition significantly improved in each group (p < 0.01 for olanzapine and risperidone, p = 0.04 for haloperidol), with no significant differences between groups. Olanzapine- and risperidone-treated patients significantly (p < 0.05) improved on domains of executive function, learning/memory, processing speed, attention/vigilance, verbal working memory, and motor functions. Additionally, risperidone-treated patients improved on domains of visuospatial memory. Haloperidol-treated patients improved only on domains of learning/memory. However, patients able to remain in treatment for the entire 52 weeks benefited more from olanzapine or risperidone treatment than haloperidol treatment.

Adolescent↗

Cognitive functioning and health as determinants of mortality in an older population.

The authors studied whether the ability of cognitive functioning to predict mortality is pervasive or specific, and they considered the role of health in the cognition-mortality association. Data were taken from a sample of 2,380 persons aged 55-85 years who took part in the Netherlands' Longitudinal Aging Study Amsterdam in 1992-1993. Five cognitive measures were distinguished: general cognitive functioning, information processing speed, fluid intelligence, learning, and proportion retained. Mortality data were obtained during an average follow-up period of 1,215 days. Cox proportional hazards regression models revealed that all cognitive functions predicted mortality independent of age, sex, education, and depressive symptoms. When health (self-rated health, medication use, physical performance, functional limitations, lung function, specific chronic diseases) was also taken into account, information processing speed, fluid intelligence, and proportion retained remained independent predictors of mortality, whereas the ability of general cognitive functioning and learning to determine mortality was lost. The authors concluded that the ability of cognitive functioning to predict mortality is pervasive to all cognitive functions that were included in the study when age, sex, education, and depressive symptoms are considered and is more specific to some functions when also controlling for health.

Activities of Daily Living↗