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Slowing of reaction time in Parkinson's disease: the involvement of the frontal lobes.

This study investigated the possibility that the previously mixed findings relating to cognitive deficits in Parkinson's disease might be attributable to inhomogeneity within the patients sampled, with attentional deficits occurring only for those Parkinson's patients who also have additional frontal lobe impairment. Twenty-five patients with idiopathic Parkinson's disease were classified as showing frontal dysfunction, or not, on the basis of their performance on the Wisconsin Card Sorting Test and the picture arrangement subtest of the WAIS. The two groups, and a control group of normal elderly subjects matched for age and IQ, undertook tests of visual attention designed to dissociate baseline response speed from central information processing speed. Error rates did not differ between the groups. Performance of the non-frontally impaired Parkinson's group was indistinguishable from that of the controls. By contrast, the 'frontally impaired' Parkinson's group responded significantly more slowly than the controls. Further analyses indicated that for the frontally-impaired Parkinson's group, information processing and automatic functions were unimpaired but there was a generalised slowing (as reflected by increased baseline response time) which may represent a non-specific global cognitive impairment. These findings suggest that the frontal lobes may be implicated in slowed response speed in Parkinson's disease.

Adult↗

Regional lobar atrophy predicts memory impairment in multiple sclerosis.

BACKGROUND AND PURPOSE: In recent studies, measures of whole brain atrophy were strongly correlated with neuropsychological testing, explaining more variance than measures of lesion burden in patients with multiple sclerosis. The relationship between regional lobar atrophy and cognitive impairment is yet to be examined. We endeavored to assess the clinical significance of regional lobar atrophy in multiple sclerosis. METHODS: In a cross-sectional study, we evaluated 31 patients with multiple sclerosis with brain MR imaging and neuropsychological testing. Impairment was determined by comparison with demographically matched healthy controls. MR imaging generated measures of lesion burden (fluid-attenuated inversion recovery hyperintense volume), general atrophy (brain parenchymal fraction), central atrophy (lateral ventricle volume), and lobar atrophy (regional brain parenchymal fraction of frontal, temporal, parietal, and occipital lobes in each hemisphere). Neuropsychological testing emphasized measures of processing speed and memory, because these are commonly affected in multiple sclerosis. RESULTS: Patients with multiple sclerosis showed significant atrophy and impairment on all neuropsychological tests. Regional atrophy accounted for the most variance in all regression models predicting memory performance. Left temporal atrophy was the primary predictor of auditory/verbal memory (partial r's = 0.55-0.61), and both left and right temporal atrophy predicted visual/spatial memory performance (partial r's = 0.51-0.67). Models predicting learning consistency retained frontal lobe atrophy measures (partial r's = 0.44-0.68). Central and general atrophy measures were the primary predictors in modeling processing speed (partial r's = 0.42-0.64). CONCLUSION: Regional atrophy accounts for more variance than lesion burden, whole brain atrophy, or lateral ventricle volume in predicting multiple sclerosis-associated memory dysfunction.

Adult↗

Improvements in cognition in patients converting from thrice weekly hemodialysis to nocturnal hemodialysis: a longitudinal pilot study.

Cognitive impairment has been documented in uremia with partial improvement after dialysis. Nocturnal daily hemodialysis (NHD) is a novel dialysis modality with multiple benefits. Previous reports have shown marked improvements in quality of life, cardiac function, resolution of peripheral vascular disease, and reversal of central sleep apnea. We hypothesized that patients maintained on NHD would have better cognitive functioning than those receiving conventional therapy. Using a longitudinal study design, patients were tested at baseline and again after >or=6 months NHD. At each of the two time points, a battery of 10 neuropsychological tests were used to evaluate three domains of cognitive functioning--attention and working memory skills, psychomotor efficiency and processing speed, and learning efficiency. Clinical subjective symptoms for cognitive functioning and depression were measured using the Patients Assessment of Own Functioning inventory and the Beck Depression Index. Twelve patients (six males, six females) were recruited. Patients were aged 39.6+/-3.3 years at the time of first testing. Thirty-three percent were diabetic, with a mean Charlson comorbidity score of 3.5+/-2.0. Depression (defined as >16 on the Beck Depression Index score) was not seen in any patient. Over the 6-month period, a 22% reduction in cognitive symptoms (P=0.01), 7% improvement in psychomotor efficiency and processing speed (P=0.02), and 32% improvement in attention and working memory (P=0.04) was seen. Learning efficiency scores were unchanged. NHD may be associated with improved general cognitive efficiency as measured by psychomotor efficiency and attention and working memory.

Adult↗

Long-term improvements in cognitive performance through computer-assisted cognitive training: a pilot study in a residential home for older people.

The aim of the present pilot study was to investigate the effects of computer-assisted cognitive training on aging-associated memory deficits, information processing speed, learning, and interference tendency in older people. Residents of a home for older people (15 women, four men; mean age 83.5; range 75-91) participated in a 14-week computer-assisted cognitive training program. The Niirnberg Aging Inventory and the California Verbal Learning Test were administered prior to the program, immediately after the program and after a period of five months to assess the effectiveness of the cognitive training. After the cognitive training program there were significant improvements in primary working memory and also secondary working memory (for verbal and visual stimuli), on parameters of information processing speed, learning and interference tendency. Improvements in the last two cognitive parameters were maintained five months after completion of the training program. The present study indicates that computerized cognitive training programs can be used in older people to achieve long-term improvements in some important aspects of fluid intelligence. It is suggested that computers could be employed more extensively to prevent and treat cognitive deficits in older people.

Aged↗

Cognition and white matter hyperintensities in older depressed patients.

OBJECTIVE: The authors compared amounts of white matter hyperintensity in late- and early-onset depressed patients and never-depressed older subjects, compared neuropsychological function in these groups, and investigated the association between white matter hyperintensities and cognitive function in depression. METHOD: Sixty currently depressed patients whose first depression occurred after age 50 years, 35 depressed patients over age 50 whose first depression occurred before age 35, and 165 nonpsychiatrically ill subjects over age 50 underwent magnetic resonance imaging (MRI) and neuropsychological evaluation. Areas of white matter hyperintensity were measured from MRI images. RESULTS: The late-onset patients had more white matter hyperintensity than either of the other groups. Compared to the nondepressed subjects, the patients had significantly lower scores in the cognitive domains of nonverbal intelligence, nonverbal memory, constructional ability, executive ability, and information processing speed. The cognitive abnormalities were mostly confined to the late-onset patients, and the presence of a large amount of white matter hyperintensity was associated with significantly poorer executive skills. However, most of the scores were not in the significantly impaired range. CONCLUSIONS: Large amounts of white matter hyperintensity are more frequent in patients with late-onsetdepression than in elderly subjects with early-onset or no depression. Both late- and early-onset elderly depressed patients show mild decrements in some "right hemisphere" cognitive skills; the late-onset subjects also show deterioration in information processing speed and executive functions. Patients with large amounts of white matter hyperintensity have significantly poorer executive function.

Age Factors↗

Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly.

OBJECTIVE: To investigate to what extent subjective memory complaints and APOE-epsilon4 allele carriage predict future cognitive decline in cognitively intact elderly persons, by evaluating both their separate and combined effects. METHODS: We selected 1,168 subjects from the population-based Longitudinal Aging Study Amsterdam who were 62 to 85 years of age and had no obvious cognitive impairment at baseline (Mini-Mental State Examination [MMSE] score, > or =27). Memory complaints and APOE phenotypes were assessed at baseline. MMSE, the Auditory Verbal Learning Test (memory: immediate recall and delayed recall), and the Alphabet Coding Task-15 (information processing speed) were used to study cognitive decline. Follow-up data were collected after 3 and 6 years. Data were analyzed with generalized estimating equations, adjusted for age, sex, education, and depression. RESULTS: Baseline memory complaints were reported by 25.5% of the cognitively intact elderly persons. Overall, 25.3% of the subjects were carriers of at least one APOE-epsilon4 allele. Memory complaints were associated with a greater rate of decline in all cognitive measures, except immediate recall. In addition, APOE-epsilon4 allele carriers had a greater rate of cognitive decline shown by MMSE scores and slower information processing speeds after 6 years. The effects of both memory complaints and APOE-epsilon4 allele carriage were additive: subjects with both factors had a two times higher cognitive decline than did subjects without both factors. CONCLUSIONS: Both memory complaints and APOE-epsilon4 allele carriage predict cognitive decline at an early stage. This finding highlights the importance of subjective memory complaints, which are important even at an early stage when objective tests are still unable to detect cognitive deficits and are especially important for elderly carriers of the APOE-epsilon4 allele because they have an additional risk.

Aged↗

The effects of antioxidants in the senescent auditory cortex.

We investigated whether a 2-month dietary supplementation of antioxidants, in the form of blueberry phytochemicals, could reverse or retard the age-related decline in temporal processing speed observed in the aged rat. To this end, extracellular single unit responses to frequency modulated (FM) sweeps were recorded in the primary auditory cortex (AI) of aged rats that had been placed on either a blueberry-supplemented or control diet 2 months prior to the physiological recordings. Results showed that most cells recorded from the blueberry-fed rats responded most vigorously to fast FM sweeps, similar to that observed in young rats. In contrast, the majority of cells recorded from the control rats showed a preference for slow FM sweep rates. These results suggest that age-related changes in temporal processing speed in A1 may be reversed by dietary supplementation of blueberry phytochemicals.

Action Potentials↗

Pulmonary function, cognitive impairment and brain atrophy in a middle-aged community sample.

OBJECTIVE: To determine the relationship of lung function to brain anatomical parameters and cognitive function and to examine the mediating factors for any relationships. METHODS: A random sub-sample of 469 persons (men = 252) aged 60-64 years from a larger community sample underwent brain magnetic resonance imaging scans and pulmonary function tests (forced vital capacity, FVC, forced expiratory volume in the first second, FEV(1)). Subjects were assessed for global cognitive function, episodic memory, working memory, information processing speed, fine motor dexterity and grip strength. The magnetic resonance imaging scans were analysed for overall brain atrophy, subcortical atrophy (ventricle-to-brain ratio, VBR), hippocampal volume, and white matter hyperintensity (WMH) volume. RESULTS: FEV(1) had a significant negative correlation with overall brain atrophy and VBR in men. The FEV(1)/FVC ratio had a significant correlation with WMHs in both men and women. In regression models that controlled for sex, age, height, level of activity, smoking, chronic respiratory disease and education, FEV(1) and FVC were significant predictors of VBR but no other structural brain measure. Pulmonary function was also significantly related to information processing speed and fine motor dexterity. Male subjects with chronic respiratory disease had more deep WMHs. Path analyses to examine if structural measures mediated between lung function and cognition, and whether markers of inflammation and oxidative stress or cortisol mediated between lung function and brain measures were negative. CONCLUSIONS: Decreased lung function is related to poorer cognitive function and increased subcortical atrophy in mid-adult life. Presence of chronic respiratory disease may be related to deep WMHs in men.

Atrophy↗

Dissociation of affect recognition and mood state from blunting in patients with schizophrenia.

The present study was designed to investigate the relationships between expression, perception, and experience of emotion in schizophrenic patients with and without affective blunting. Cognitive processing speed, emotional perception, and emotional experience were assessed in 25 schizophrenic patients grouped according to scores on a measure of overt emotional expression (Rating Scale for Emotional Blunting). Results showed dissociation of emotional expression from emotional perception and emotional experience. Blunted schizophrenic patients were no more impaired in the perception of emotion (Profile of Nonverbal Sensitivity) than non-blunted schizophrenic patients. In addition, groups did not differ in intensity of emotional experience as quantified on the self-report of arousal state (Positive and Negative Affect Scales). Accuracy of perception and reported experience of emotion did not differ between groups as a function of emotional valence. Cognitive processing speed (Symbol Digit Modalities Test; SDMT) was related to blunting score and to perception accuracy, although the SDMT did not differ between groups. Results are discussed in terms of a neuropathological basis for impairment of emotional expression.

Adult↗

Factor structure of nonverbal cognition.

In order to define the factor structure of nonverbal cognitive processes, 156 twenty to sixty year-old participants were selected in Medellin (Colombia). A neuropsychological test battery for assessing different nonverbal cognitive domains (attention, memory, visuoperceptual and visuoconstructive abilities. executive functions, praxis abilities, and written calculation abilities) was administered. Initially, independent factor analyses were carried out for each domain. Three attention factors (Sustained Attention, Divided Attention, and Processing Speed, 73.1% of the variance); two memory factors (Categorical and Non-Categorical Memory, 59.7% of the variance): two visuoperceptual and visuoconstructive factors (Sequential and Simultaneous, 54.0% of the variance); and two executive function factors (Categorization and Trial Error, 82.0% of the variance) were found. Further, several sequential factor analyses using Varimax orthogonal rotations for noncorrelated variables were performed. The 32 test variables were included, but progressively some variables were removed. This procedure finally selected 13 variables corresponding to five factors accounting for 72.6% of variance. Factor I was an Executive Function factor (30% of variance). Factor 2 corresponded to a Sequential Constructional factor (14.7%). Factor 3 represented a Processing Speed factor and accounted for 10.6% of the variance. Factor 4 was Visuoperceptual factor (9.5% of the variance). Finally, Factor 5 (7.8% of the variance) was a Nonverbal Memory factor. It was concluded that several, different cognitive dimensions are included in nonverbal cognition.

Adult↗

Is autism due to brain desynchronization?

The hypothesis is presented that a disruption in brain synchronization contributes to autism by destroying the coherence of brain rhythms and slowing overall cognitive processing speed. Particular focus is on the inferior olive, a precerebellar structure that is reliably disrupted in autism and which normally generates a coherent 5-13 Hz rhythmic output. New electrophysiological data reveal that the continuity of the rhythmical oscillation in membrane potential generated by inferior olive neurons requires the formation of neuronal assemblies by the connexin36 protein that mediates electrical synapses and promotes neuronal synchrony. An experiment with classical eyeblink conditioning is presented to demonstrate that the inferior olive is necessary to learn about sequences of stimuli presented at intervals in the range of 250-500 ms, but not at 700 ms, revealing that a disruption of the inferior olive slows stimulus processing speed on the time scale that is lost in autistic children. A model is presented in which the voltage oscillation generated by populations of electrically synchronized inferior olivary neurons permits the utilization of sequences of stimuli given at, or faster than, 2 per second. It is expected that the disturbance in inferior olive structure in autism disrupts the ability of inferior olive neurons to become electrically synchronized and to generate coherent rhythmic output, thereby impairing the ability to use rapid sequences of cues for the development of normal language skill. Future directions to test the hypothesis are presented.

Animals↗

Working memory deficits in multiple sclerosis: comparison between the n-back task and the Paced Auditory Serial Addition Test.

Working memory (WM) deficits are common in multiple sclerosis (MS). The Paced Auditory Serial Addition Test (PASAT) is used frequently to measure WM in clinical settings. The n-back paradigm is used often in experimental studies of WM. One unique component of the n-back task is that it provides a measure of reaction time (RT), an additional behavioral index of processing speed and task difficulty. Despite the use of both tasks to measure WM, their common variance has not been documented. We tested 32 MS patients and 20 controls; performance measures were obtained for both tasks. Compared with controls, MS patients generally had poorer performance on both the PASAT and n-back task. MS patients also had slower RTs on the n-back than controls and showed more slowing than controls as a function of WM load. Correlational analyses showed a high correspondence between performance measures on the PASAT and n-back. Principal components analysis pointed to a common feature of the PASAT, n-back, and specific other neuropsychological measures, that is, processing speed. Although the PASAT and n-back were shown to have a significant amount of shared variance, each test has specific advantages and disadvantages for use in clinical populations.

Acoustic Stimulation↗

Neuropsychological effects of hyperbaric oxygen therapy in cerebral palsy.

We conducted a double-blind placebo study to investigate the claim that hyperbaric oxygen treatment (HBO2) improves the cognitive status of children with cerebral palsy (CP). Of 111 children diagnosed with CP (aged 4 to 12 years), only 75 were suitable for neuropsychological testing, assessing attention, working memory, processing speed, and psychosocial functioning. The children received 40 sessions of HBO2 or sham treatment over a 2-month period. Children in the active treatment group were exposed for 1 hour to 100% oxygen at 1.75 atmospheres absolute (ATA), whereas those in the sham group received only air at 1.3 ATA. Children in both groups showed better self-control and significant improvements in auditory attention and visual working memory compared with the baseline. However, no statistical difference was found between the two treatments. Furthermore, the sham group improved significantly on eight dimensions of the Conners' Parent Rating Scale, whereas the active treatment group improved only on one dimension. Most of these positive changes persisted for 3 months. No improvements were observed in either group for verbal span, visual attention, or processing speed.

Attention↗

The relationship between pain and mental flexibility in older adult pain clinic patients.

OBJECTIVE: Persistent pain and cognitive impairment are each common in older adults. Mental flexibility, memory, and information-processing speed may be particularly vulnerable in the aging brain. We investigated the effects of persistent pain on these cognitive domains among community-dwelling, nondemented older adults. SETTING: Older Adult Pain Management Program. DESIGN: A total of 56 new patients (mean age 76.1 years) were recruited to describe 1) rates of persistent pain conditions and pain intensity; 2) cognition (mental flexibility, short-term memory, and psychomotor speed); 3) severity of depression; and 4) sleep quality. All patients had nonmalignant pain for at least 3 months. Pain intensity was measured with the McGill Pain Questionnaire and depression severity with the 17-item Hamilton Rating Scale for Depression. Cognition was assessed with 1) Mini-Mental State Exam; 2) Number-Letter-Switching and Motor Speed subtests of the Delis-Kaplan Executive Function System Trail Making Test; 3) Digit Symbol Subtest (DSST) of the Wechsler Adult Intelligence Scales-III; and 4) free and paired recall of the DSST digit-symbol pairs. Multiple linear regression modeled whether these variables predicted poorer cognitive outcomes, after adjusting for the effects of opioids, sleep impairment, depression, medical comorbidity, and years of education. RESULTS: In univariate analysis, pain severity was associated with a greater impairment on number-letter switching (r = -0.42, P = 0.002). This association remained after adjusting for the effects of depression, sleep, medical comorbidity, opioid use, and years of education (t = -1.97, P = 0.056). CONCLUSIONS: In community dwelling older adults, neither pain nor mood was associated with measures of short-term memory or information-processing speed. However, pain severity was associated with decreased performance on a test of number-letter switching, indicating a relationship between pain and mental flexibility.

Aged↗

Demographically adjusted normative standards for new indices of performance on the Paced Auditory Serial Addition Task (PASAT).

The Paced Auditory Serial Addition Task (PASAT) is a complex cognitive test sensitive to neuropsychological disorders. Its traditional Total Correct score seemingly reflects multiple cognitive abilities, including attention, working memory, and processing speed. Snyder, Aniskiewicz, and Snyder (1993) modified scoring guidelines for the PASAT to give credit only for "dyads." This method emphasizes working memory operations and has been found superior to Total Correct scores at detecting cognitive impairments in several investigations. To date, normative standards are not available for the "dyad" scoring method, thus limiting its utility in clinical and research settings. The current investigation provides demographically adjusted normative data based on a sample of 500 healthy adults of varied age, education, sex, and race (African American and Caucasian) for various indices of performance on the PASAT, including "Total Dyads" obtained across the four PASAT trials. In addition, we describe and present normative data on four other indices designed to quantify various aspects of performance on the PASAT: invalid responding, effects of varied information processing speed demands, and tendency to omit responses and to make arithmetic errors.

Abstracting and Indexing↗

Usability of a theory of visual attention (TVA) for parameter-based measurement of attention I: evidence from normal subjects.

The present study investigated the usability of whole and partial report of briefly displayed letter arrays as a diagnostic tool for the assessment of attentional functions. The tool is based on Bundesen's (1990, 1998, 2002; Bundesen et al., 2005) theory of visual attention (TVA), which assumes four separable attentional components: processing speed, working memory storage capacity, spatial distribution of attention, and top-down control. A number of studies (Duncan et al., 1999; Habekost & Bundesen, 2003; Peers et al., 2005) have already demonstrated the clinical relevance of these parameters. The present study was designed to examine whether (a) a shortened procedure bears sufficient accuracy and reliability, (b) whether the procedures reveal attentional constructs with clinical relevance, and (c) whether the mathematically independent parameters are also empirically independent. In a sample of 35 young healthy subjects, we found high intraparameter correlations between full- and short-length tests and sufficient internal consistencies as measured via a bootstrapping method. The clinical relevance of the TVA parameters was demonstrated by significant correlations with established clinical tests measuring similar constructs. The empirical independence of the four TVA parameters is suggested by nonsignificant or, in the case of processing speed and working memory storage capacity, only modest correlations between the parameter values.

Adult↗

Recovery in pediatric brain injury: is psychostimulant medication beneficial?

OBJECTIVE: To assess the effects of methylphenidate on attention, memory, behavior, processing speed, and psychomotor skills of children with closed head injuries. DESIGN: Double-blind, placebo-controlled, crossover design. SETTING: An outpatient facility of a children's hospital medical center. PATIENTS: Ten pediatric subjects identified through chart review. Subjects met baseline scores for hyperactivity (Conner's Hyperactivity Index greater than or equal to 60) and intellectual functioning (Verbal Intelligence Quotient greather than or equal to 70) and achieved minimal scores on two psychometric tests. All subjects evidenced head injury by focal lesions on computed tomography scan and/or sequelae reported at the time of injury. Severity of injury ranged from mild to severe. All subjects were medically stable at the time of testing. Mean time post injury was 2 years, 8 months. INTERVENTION: Administration of methylphenidate and placebo. MAIN OUTCOME MEASURES: Percentage change in scores was calculated to assess differences between baseline and end of methylphenidate/placebo trials. RESULTS: No significant differences between methylphenidate and placebo on measures assessing behavior, attention, memory, and processing speed. CONCLUSIONS: The results of the study call into question the effectiveness of methylphenidate in the pediatric head injury population.

Adolescent↗

Does aspirin or other NSAIDs reduce the risk of cognitive decline in elderly persons? Results from a population-based study.

OBJECTIVE: To investigate the protective effect of NSAIDs and aspirin separately on cognitive decline in elderly subjects, controlling for consistent use of these agents over a prolonged period of time. METHODS: The study sample consisted of 1007 subjects, drawn from a population-based random sample of elderly individuals, 62-85 years old, who participated in a 3-year follow-up study. From this sample subjects were selected, who did use NSAIDs and completed all cognitive tests at both measurements (n=137), and subjects who did not use NSAIDs and completed all cognitive tests (n=475). Cognitive tests included the Mini-Mental State Examination (MMSE), tests for episodic memory (Auditory Verbal Learning Test) and information processing speed (coding task). Cognitive decline was computed using Edwards-Nunnally method. Multiple logistic regression analyses were performed to examine the association between NSAID (with and without aspirin) and decline in cognitive performance. Besides, the interaction of NSAIDs with age on cognitive decline was determined. RESULTS: The relative risk estimates of decline in episodic memory (immediate recall) adjusted for age, gender, education, baseline MMSE, vascular diseases, diabetes mellitus and (rheumatoid) arthritis for aspirin users only was more than three times reduced (OR: 0.30, 95% CI: 0.09-0.82). The odds ratio for decline in memory of NSAID use without aspirin, adjusted for age, gender, education, baseline MMSE, vascular diseases, diabetes mellitus and (rheumatoid) arthritis was not significant (OR: 1.00, 95% CI: 0.39-2.93). The effect of aspirin was significant only in persons of 75 years and over (OR: 0.10, 95% CI: 0.01-0.81), not in subjects younger than 75 years (OR: 0.52, 95% CI: 0.14-1.96). NSAIDs did not have benefit on information processing speed. In 92% of aspirin users a low dose of 100mg daily or less was used. CONCLUSION: Low-dose aspirin might be protective for decline in memory in individuals of 75 years and over. The benefit of a low-dose aspirin does not support an anti-inflammatory effect, but suggests an antiplatelet effect. Therefore, a possible protective effect of low-dose aspirin on cognitive decline is likely only in subjects with aspirin use over a prolonged period of time.

Aged↗