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Rehabilitation of endogenous task shift processes in closed head injury patients.

This paper reports a study that was aimed to rehabilitate executive functions in CHI patients. When a subject is engaged in two speeded tasks, not simultaneously but with some form of alternation, the response is slower to an item of task A if it was preceded by an item of task B, than when it was preceded by an item of task A. This shift cost is small when subjects can prepare in advance for the new task (endogenous task shift), whereas the cost is much greater when preparation is not possible (exogenous task shift). The groups tested comprised 20 severe closed head injury (CHI) patients (10 who underwent treatment and 10 controls), 8 mild CHI patients, and 18 non-brain damaged (NBD) controls. In the present study, the shift cost was greater for severe CHI patients than for NBD controls. Treatment consisted of five sessions, in which an endogenous task shift paradigm was used. A significant reduction of the endogenous shift cost from assessment to retest was found. The reduction remained stable at the 4-month follow-up session. These results are not simply due to retesting, as the control patients did not show any improvement at retest. Interestingly, no reduction of exogenous task shift cost was found. The results showed also that the beneficial effect of the treatment generalises to other executive functions.

Adolescent↗

Towers of Hanoi and London: is the nonshared variance due to differences in task administration?

Although it has been assumed that the Tower of Hanoi and Tower of London are more or less interchangeable tasks dependent on executive function, a series of studies in our laboratory have indicated substantial nonshared variance between the performances on the two tasks. The purpose of the present study was to examine how much methods of administration, such as number of trials per problem, contribute to this nonshared variance. A new one-trial version of the Tower of Hanoi was developed to be identical to the Tower of London in four procedural characteristics. The one-trial version of the Tower of Hanoi was administered to 39 normal adults along with the traditional Tower of Hanoi and the Tower of London-Revised in two test sessions 5-7 weeks apart. The correlations between the two tasks were in the same range as found previously with the traditional task, indicating that administration differences do not account for the nonshared variance between the tasks. A reliability analysis of the one-trial tasks showed poor internal consistency. Also, the internal consistency of the 6-trial tower was artificially inflated by aspects of the administration and scoring procedures. Moreover, this task exhibited a ceiling effect on repeated testing. These results suggest that it would be of value to redesign the one-trial Tower of Hanoi systematically to increase its reliability and, potentially, its validity as a measure of executive functions.

Adult↗

Cingulate gyrus volume and metabolism in the schizophrenia spectrum.

BACKGROUND: The cingulate gyrus, which is involved in affect, attention, memory and higher executive functions, has been implicated as a dysfunctional region in schizophrenia. Postmortem studies report cytoarchitectural changes in the anterior cingulate gyrus (ACG) and functioning imaging studies show correlations between the degree of hypometabolism of the anterior cingulate and clinical symptoms in schizophrenia. METHODS: Unmedicated patients with schizophrenia (n=27) and schizotypal personality disorder (SPD) (n=13), as well as sex- and age-matched control subjects (n=32), were studied with (18)F-fluorodeoxyglucose positron emission tomography (PET) scans and magnetic resonance imaging (MRI). As a control over mental activity, all subjects performed a verbal working memory task during the PET protocol. The cingulate gyrus was first outlined on the MRI scans and, after coregistration, the coordinates were applied to the PET scans to yield a three-dimensional metabolic map of the cingulate gyrus for each subject. A statistical resampling method was used to analyze the metabolic differences between groups. RESULTS: Compared with controls, patients with schizophrenia had lower relative glucose metabolic rates in the left anterior cingulate and the right posterior cingulate gyrus (PCG) assessed by 3-D significance probability mapping. SPD patients had higher glucose metabolic rates (GMRs) in the left posterior cingulate than did controls. Furthermore, volumetric measurement with MRI showed the left anterior cingulate and Brodmann area 24' to be smaller in schizophrenic patients than controls. CONCLUSIONS: Compared with controls, patients with schizophrenia have metabolic and volumetric reductions in a cingulate gyrus area that is related to higher executive functions. Schizotypal patients rely more on sensory association areas to perform a cognitive task than do controls and seem to be a group that is partially distinct in its physiological and functional characteristics.

Adult↗

Synaptic Mitochondrial Oxidative Stress Contributes to Individual Variability in Age-Related Cognitive Inflexibility in Mice.

Aging is associated with impairments in cognitive flexibility, a key executive function supported by the medial prefrontal cortex (mPFC), yet the biological mechanisms underlying individual variability in age-related decline remain poorly understood. Here we investigated behavioral, ultrastructural, and proteomic correlates of cognitive inflexibility in mice across aging. Using a touchscreen-based attentional set-shifting task, we observed substantial individual variability in cognitive inflexibility among aged C57BL/6J mice. Volume electron microscopy of the mPFC revealed age-related reductions in synaptic density, but these structural changes did not correlate with cognitive performance. Instead, the proportion of synapses containing presynaptic mitochondria was inversely associated with cognitive flexibility in aged mice. To identify molecular correlates, we performed proteomic profiling of mPFC whole tissue and synaptosome fractions. Proteins associated with individual variability in cognitive inflexibility were largely distinct from those associated with chronological aging. Notably, synaptosomal proteins negatively correlated with cognitive performance were strongly enriched for mitochondrial pathways, including oxidative phosphorylation, mitochondrial translation, and the tricarboxylic acid cycle. Consistent with these findings, the mitochondria-targeted antioxidant MitoQ improved attentional set-shifting performance in aged mice without affecting initial learning. Proteomic analyses revealed that MitoQ reduced the abundance of synaptosomal mitochondrial proteins, particularly those involved in mitochondrial apoptotic signaling. Together, these results suggest that synaptic mitochondrial oxidative stress in the mPFC contributes to individual vulnerability to cognitive inflexibility. Targeting synaptic mitochondrial oxidative stress may therefore represent a promising strategy to preserve executive function during aging.

Animals↗

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

Diffusion MRI derived free-water (FW) metrics show promise in predicting cognitive impairment and decline in aging and Alzheimer's disease (AD). FW is sensitive to subtle changes in brain microstructure, so it is possible these measures may be more sensitive than traditional structural neuroimaging biomarkers. In this study, we examined the associations among FW metrics (measured in the hippocampus and two AD signature meta-ROIs) with cognitive performance, and compared FW findings to those from more traditional neuroimaging biomarkers of AD. We leveraged data from a longitudinal cohort (nparticipants = 296, nobservations = 870, age at baseline: 73 ± 7 years, 40% mild cognitive impairment [MCI]) of older adults who underwent serial neuropsychological assessment (episodic memory, information processing speed, executive function, language, and visuospatial skills) and brain MRI over a maximum of four time points, including baseline (n = 284), 18-month (n = 246), 3-year (n = 215), and 5-year (n = 125) visits. The mean follow-up period was 2.8 ± 1.3 years. Structural MRI was used to quantify hippocampal volume, in addition to Schwarz and McEvoy AD Signatures. FW and FW-corrected fractional anisotropy (FAFWcorr) were quantified in the hippocampus (hippocampal FW) and the AD signature areas (SchwarzFW, McEvoyFW) from diffusion-weighted (dMRI) images using bi-tensor modeling (FW elimination and mapping method). Linear regression assessed the association of each biomarker with baseline cognitive performance. Additionally, linear mixed-effects regression assessed the association between baseline biomarker values and longitudinal cognitive performance. A subsequent competitive model analysis was conducted on both baseline and longitudinal data to determine how much additional variance in cognitive performance was explained by each biomarker compared to the covariate only model, which included age, sex, race/ethnicity, apolipoprotein-ε4 status, cognitive status, and modified Framingham Stroke Risk Profile scores. All analyses were corrected for multiple comparisons using an FDR procedure. Cross-sectional results indicate that hippocampal volume, hippocampal FW, Schwarz and McEvoy AD Signatures, and the SchwarzFW and McEvoyFW metrics are all significantly associated with memory performance. Baseline competitive model analyses showed that the McEvoy AD Signature and SchwarzFW explain the most unique variance beyond covariates for memory (ΔRadj 2 = 3.47 ± 1.65%) and executive function (ΔRadj 2 = 2.43 ± 1.63%), respectively. Longitudinal models revealed that hippocampal FW explained substantial unique variance for memory performance (ΔRadj 2 = 8.13 ± 1.25%), and outperformed all other biomarkers examined in predicting memory decline (pFDR = 1.95 x 10-11). This study shows that hippocampal FW is a sensitive biomarker for cognitive impairment and decline, and provides strong evidence for further exploration of this measure in aging and AD.

Alzheimer’s disease (AD)↗

Cognitive biases toward alcohol-related words and executive deficits in polysubstance abusers with alcoholism.

AIM: To study cognitive biases for alcohol-related cues on executive function tasks involving mental flexibility and response inhibition in polysubstance abusers with alcoholism. DESIGN: The responses to alcohol-related cues of detoxified polysubstance abusers with alcoholism and of non-addicts were compared. SETTING: The University of Iowa City, Iowa, USA. PARTICIPANTS: Thirty detoxified polysubstance abusers with alcoholism (PSA) and 30 healthy non-substance abusers (CONT). MEASUREMENTS: Using the 'Alcohol Shifting Task', a variant of the go/no-go paradigm, we measured the response times and the accuracy of responses to targets and distracters. Sometimes the alcohol-related words were the targets for the 'go' response, with neutral words as distracters, sometimes the reverse. Several shifts in the type of the target occurred during the task. FINDINGS: Relative to CONT, PSA were generally slower to respond to targets, but the group difference was smaller when alcohol-related words were the targets. A signal detection analysis also indicated that relative to CONT, the PSA had more difficulties discriminating between targets and distracters (low d'), and they showed more signs of decision bias (low C), reflecting increased readiness to respond to both targets and distracters. However, these discrimination and inhibition deficits were more pronounced when alcohol-related words were the targets. Furthermore, the weaknesses in RT and C were more pronounced in PSA after shifting the targets from alcohol-related to neutral words, or vice versa. CONCLUSIONS: These results suggest that PSA have cognitive biases towards information related to alcohol, and that these biases, as well as the poor executive functions (lower mental flexibility and response inhibition) revealed in PSA might be responsible for their failure to maintain abstinence.

Adult↗

Effects of home visits by paraprofessionals and by nurses: age 4 follow-up results of a randomized trial.

OBJECTIVE: To examine the effects of prenatal and infancy home visiting by paraprofessionals and by nurses from child age 2 through age 4 years. METHODS: We conducted, in public and private care settings in Denver, Colorado, a randomized, controlled trial with 3 arms, ie, control, paraprofessional visits, and nurse visits. Home visits were provided from pregnancy through child age 2 years. We invited 1178 consecutive, low-income, pregnant women with no previous live births to participate, and we randomized 735; 85% were unmarried, 47% Mexican American, 35% white non-Mexican American, 15% black, and 3% American Indian/Asian. Outcomes consisted of maternal reports of subsequent pregnancies, participation in education and work, use of welfare, marriage, cohabitation, experience of domestic violence, mental health, substance use, and sense of mastery; observations of mother-child interaction and the home environment; tests of children's language and executive functioning; and mothers' reports of children's externalizing behavior problems. RESULTS: Two years after the program ended, women who were visited by paraprofessionals, compared with control subjects, were less likely to be married (32.2% vs 44.0%) and to live with the biological father of the child (32.7% vs 43.1%) but worked more (15.13 months vs 13.38 months) and reported a greater sense of mastery and better mental health (standardized scores [mean = 100, SD = 10] of 101.25 vs 99.31 and 101.21 vs 99.16, respectively). Paraprofessional-visited women had fewer subsequent miscarriages (6.6% vs 12.3%) and low birth weight newborns (2.8% vs 7.7%). Mothers and children who were visited by paraprofessionals, compared with control subjects, displayed greater sensitivity and responsiveness toward one another (standardized score [mean = 100, SD = 10] of 100.92 vs 98.66) and, in cases in which the mothers had low levels of psychologic resources at registration, had home environments that were more supportive of children's early learning (score of 24.63 vs 23.35). Nurse-visited women reported greater intervals between the births of their first and second children (24.51 months vs 20.39 months) and less domestic violence (6.9% vs 13.6%) and enrolled their children less frequently in preschool, Head Start, or licensed day care than did control subjects. Nurse-visited children whose mothers had low levels of psychologic resources at registration, compared with control group counterparts, demonstrated home environments that were more supportive of children's early learning (score of 24.61 vs 23.35), more advanced language (score of 91.39 vs 86.73), superior executive functioning (score of 100.16 vs 95.48), and better behavioral adaptation during testing (score of 100.41 vs 96.66). There were no statistically significant effects of either nurse or paraprofessional visits on the number of subsequent pregnancies, women's educational achievement, use of substances, use of welfare, or children's externalizing behavior problems. CONCLUSIONS: Paraprofessional-visited mothers began to experience benefits from the program 2 years after the program ended at child age 2 years, but their first-born children were not statistically distinguishable from their control group counterparts. Nurse-visited mothers and children continued to benefit from the program 2 years after it ended. The impact of the nurse-delivered program on children was concentrated on children born to mothers with low levels of psychologic resources.

Birth Intervals↗

[Deficits in memory retrieval: an argument in favor of frontal subcortical dysfunction in depression].

UNLABELLED: While numerous studies have objective quantitative and qualitative deficits of memory in depressed patients, the mechanisms of these impairments are not well established. The study reported here was designed to assess encoding and retrieval processes in depression and to define the specific nature of memory failure associated with this disorder. METHODS: Ten inpatients with major depression responding to DSM III-R criteria and ten normal controls were included in this study. All subjects were assessed with a neuropsychological battery including: a) subtests of Weschsler memory scale (digit span, logical memory); b) verbal fluency (letter); c) two tasks assessing executive functions (cognitive estimate, Nelson's test); d) two explicit tasks of verbal learning (California Verbal Learning Test and Grober & Buschke's procedure) which measure memory performance in various conditions of encoding (incidental vs controlled) and of recollection (free recall, cued recall and recognition). Severity of depression was assessed with the MADRS and the Retardation Rating Scale for Depression. RESULTS: Although there was no difference between patients and controls on digit span and logical memory tasks, depressed patients exhibited a deficit in verbal learning with CVLT and Grober & Buschke's procedure. On California Verbal Learning Test, depressive subjects performed poorly in free recall and demonstrated poor consistency. Patients show free recall improvement across trials 1 or 5 and this learning effect didn't differ from controls. Score of patients and controls on cued recall and recognition were at the same level. Grober & Buschke's procedure confirmed these results. Despite a control of encoding processes during the initial presentation of the words, free recall measure revealed significant difference between groups. Like controls, patients recalled almost all items when semantic cues was provided and their recognition results showed a ceiling effect. Consistency indexes of free recall and cued recall differed significantly between groups. Verbal fluency and frontal tasks didn't allow to distinguish the depressive patients from controls. DISCUSSION: Depressive subjects exhibited a deficit in free recall and poor consistency while cued recall and recognition were normal. Patient's results in free recall are characterized by difficulties in planning and in maintaining retrieval strategies. These findings suggest that memory failure in depression could reflect an impairment in retrieval processes depending on executive functions controlled by the subcortical structures.

Adult↗

The differentiation of mild frontotemporal dementia from Alzheimer's disease and healthy aging by neuropsychological tests.

BACKGROUND: Frontotemporal dementia (FTD) is difficult to diagnose in the early stages and may be misdiagnosed as Alzheimer's disease (AD) or as a psychiatric disorder. This study aimed to investigate neuropsychological function in FTD of mild severity and compare it to that of mild AD and healthy control participants. METHODS: The study comprised 11 individuals with FTD, 29 with AD and 27 healthy controls. Participants completed a comprehensive neuropsychological assessment in which each area of cognitive function was examined with several widely used clinical tests. Test scores were converted to age-corrected scaled scores and combined to form indices for six areas of cognitive function. These indices were attention, psychomotor speed, memory acquisition, memory recall, executive function and constructional ability. RESULTS: The FTD group performed below the level of the controls in all areas except constructional ability. FTD and AD groups showed distinct patterns of neuropsychological performance. The FTD group showed predominantly executive dysfunction with less impaired memory function, while the AD group showed the opposite pattern. The capacity of the tests to discriminate between groups was good overall, with 90% of the total sample correctly classified. Predictive success for the FTD group was 64%, given a base rate of 16%. CONCLUSION: Administration of a comprehensive neuropsychological protocol including several tests of executive function allows increased certainty about accurate clinical diagnosis of mild FTD.

Aged↗

Verbal intrusions precede memory decline in adults with Down syndrome.

BACKGROUND: Verbal intrusion errors are irrelevant responses made in the course of verbal memory retrieval or language production that have been associated with disruption of executive functions and the prefrontal cortex. They have been observed to occur more frequently both with normal aging and with neurodegenerative diseases such as Alzheimer's disease (AD). The purpose of this study was to longitudinally examine the production of verbal intrusions among middle-aged adults with Down syndrome (DS) and unspecified intellectual disability (ID) to determine whether producing verbal intrusions at one point in time was related to subsequent verbal memory performance. Because of the combination of a relative deficit in verbal working memory (WM), premature aging, and higher risk of AD among adults with DS, it was predicted that they would make more verbal intrusions than adults with unspecified ID. METHODS: Word List recall (WLR), the Selective Reminding Test (SRT), and the Cued Recall Test (CRT), were administered three times at 18-month intervals during a 3-year period. In Analysis 1, aetiology differences in making intrusion errors were examined. Twenty-three adults with unspecified ID in the moderate to mild range [time 1(T1) mean age = 47.2 years] and 42 adults with DS (T1 mean age = 44.3) participated. WLR is a serial WM task beginning at two word sequences and progressively increasing by one word every three trials. WLR intrusions were analysed because they were least likely to include 'educated guesses' because this test is not based on semantic categories. In Analysis 2, we only examined participants with DS. They were divided into two groups, 16 individuals who made at least one intrusion error at T1 (T1 mean age = 45.8) and 26 who did not (T1 mean age = 43.3). Longitudinal performance for these groups was analysed to determine whether the group that intruded at T1 did more poorly on subsequent memory tests. RESULTS: A higher proportion of responses comprised intrusions for the group with DS and a higher percentage of the participants with DS made at least one intrusion error when compared with participants with unspecified ID (74% and 44% respectively). Those participants with DS who made at least one intrusion error at T1 showed a subsequent decline in performance on both WLR and the SRT. CONCLUSIONS: The production of intrusion errors during a verbal WM task is a characteristic of middle-aged adults with DS. This suggests compromised executive function and control of inhibition within the verbal modality for this group. Further, verbal intrusions are a qualitative aspect of verbal processing that merit attention in considering the issue of deficiencies of language and verbal WM abilities among people with DS. Last, and perhaps most importantly, although not definitive diagnostically, an increase in verbal intrusions is a potentially noteworthy signal when evaluating the cognitive health of adults with DS.

Adult↗

Assessing cognitive function: a guide to neuropsychological testing.

Neuropsychology is a discipline that studies brain-behavior relations through laboratory testing of behavior. Neuropsychologists develop a comprehensive clinical description of the person's cognitive processes and their implications for everyday behavior. Nurses can use the results of neuropsychological assessments as an objective source of information when planning care for clients who are cognitively impaired. This article provides an introduction to neuropsychology as a discipline, to its tests, and to its methods of assessment and interpretation. Two standard test batteries, the Halstead-Reitan Battery and the Luria-Nebraska Neuropsychological Battery, are described. Special tests for many cognitive functions--such as attention, executive functions, sensation and perception, motor performance, memory, language, and intelligence--also are described.

Adult↗

Long-term benefits of rivastigmine in dementia associated with Parkinson's disease: an active treatment extension study.

In patients with dementia associated with Parkinson's disease (PD), the efficacy and safety of rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, were previously demonstrated in a 24-week double-blind placebo-controlled trial. Our objective was to determine whether benefits were sustained over the long term. Following the double-blind trial, all patients were permitted to enter an active treatment extension study, during which they received rivastigmine 3-12 mg/day. Standard safety assessments were performed. Efficacy assessments included the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and other measures of cognition, daily function, neuropsychiatric symptoms, and executive function. Of 433 patients who completed the double-blind trial, 334 entered and 273 completed the active treatment extension. At 48 weeks, the mean ADAS-cog score for the whole group improved by 2 points above baseline. Placebo patients switching to rivastigmine for the active treatment extension experienced a mean cognitive improvement similar to that of the original rivastigmine group during the double-blind trial. The adverse event profile was comparable to that seen in the double-blind trial. Long-term rivastigmine treatment appeared well tolerated and may provide sustained benefits in dementia associated with PD patients who remain on treatment for up to 48 weeks.

Activities of Daily Living↗

Executive brain functions after exposure to nocturnal traffic noise: effects of task difficulty and sleep quality.

The after-effects of nocturnal traffic noise on cognitive performance and inhibitory brain activity were investigated. Twenty participants (18-30 years) performed an easy and a difficult visual Go/Nogo task with simultaneous EEG recording after a quiet night and then during three nights when aircraft noise was presented with equivalent noise levels of 39, 44, and 50 dBA, respectively, between 11 p.m. to 7 a.m. Based on subjective sleep quality rating, participants were separated into "good" versus "bad" sleepers. The performance and inhibition-related components (N2, P3) of event-related potentials were analysed. The N2 and P3 amplitudes were smaller and latencies were prolonged in the difficult than in the easy task. This effect was more pronounced for Nogo than for Go trials. The Nogo-P3 amplitude was smaller in Noise than in "Quiet" conditions in the difficult task only. In the difficult task, the Nogo-P3 latency was prolonged in bad sleepers than in good sleepers. The Nogo-P3 amplitude was reduced in Noise as compared to "Quiet" conditions in bad sleepers only. Sleep quality in bad sleepers worsened steadily with increasing noise levels. No effects of noise or subjective sleep quality on performance were found. Inhibitory processes appear to be selectively impaired after nocturnal noise exposure. The task difficulty and perceived sleep quality are important factors modulating noise effects. The results suggest that nocturnal traffic noise increase physiological costs for inhibitory functioning on the day even if no overt performance decrement is observed.

Action Potentials↗

SpHnf6, a transcription factor that executes multiple functions in sea urchin embryogenesis.

The Strongylocentrotus purpuratus hnf6 (Sphnf6) gene encodes a new member of the ONECUT family of transcription factors. The expression of hnf6 in the developing embryo is triphasic, and loss-of-function analysis shows that the Hnf6 protein is a transcription factor that has multiple distinct roles in sea urchin development. hnf6 is expressed maternally, and before gastrulation its transcripts are distributed globally. Early in development, its expression is required for the activation of PMC differentiation genes such as sm50, pm27, and msp130, but not for the activation of any known PMC regulatory genes, for example, alx, ets1, pmar1, or tbrain. Micromere transplantation experiments show that the gene is not involved in early micromere signaling. Early hnf6 expression is also required for expression of the mesodermal regulator gatac. The second known role of hnf6 is its participation after gastrulation in the oral ectoderm gene regulatory network (GRN), in which its expression is essential for the maintenance of the state of oral ectoderm specification. The third role is in the neurogenic ciliated band, which is foreshadowed exactly by a trapezoidal band of hnf6 expression at the border of the oral ectoderm and where it continues to be expressed through the end of embryogenesis. Neither oral ectoderm regulatory functions nor ciliated band formation occur normally in the absence of hnf6 expression.

Amino Acid Sequence↗

Quantitative genetic modeling of regional brain volumes and cognitive performance in older male twins.

As part of an ongoing longitudinal twin study, data from both MRI brain scanning and from neuropsychological testing were obtained from 139 male-male twin pairs (72 monozygotic [MZ] and 67 dizygotic [DZ]), 69-80 years old at the time of examination. For descriptive purposes, we examined the MZ and DZ intraclass correlations (ICC) of four lobar brain volumes (frontal, temporal, parietal, and occipital), two cerebrospinal fluid (CSF) volumes (lateral ventricle and temporal horn of the lateral ventricles), and two measures of cognitive functioning (verbal memory and executive function). We found that for lobar brain and CSF space volumes, the MZ ICC were significantly greater than zero (r=0.37-0.77) and greater than the corresponding DZ correlations (r=0.02-0.49). Similarly, within-pair correlations for the two neuropsychological factors were statistically significant and significantly larger in MZ twin pairs than in DZ pairs, suggesting the presence of genetic variance. Bivariate genetic analysis revealed that while close to 60% of individual differences in neuropsychological performance were due to genetic influences, less than 50% of genetic effects were in common with those influencing brain volumes. These data may shed light on the genetic liability for brain diseases that affect the elderly.

Aged↗

Apolipoprotein E and cognitive performance: a meta-analysis.

The epsilon4 allele of the apolipoprotein E (APOE) gene is a known risk factor for Alzheimer's disease and may also affect cognitive performance in normal aging. Evidence of the presence and magnitude of epsilon4-related cognitive deficits was examined with a meta-analysis of the available literature. Thirty-eight studies were included, and cognitive performance was collapsed into 8 domains. Results indicated significant APOE-epsilon4 group differences for global cognitive functioning, episodic memory, and executive functioning, in favor of non-epsilon4 carriers. In addition, older age and APOE-epsilon4 heterozygosity was associated with smaller epsilon4-related impairments. The meta-analysis results suggest that APOE-epsilon4 genotype does affect cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance.

Adult↗

[Cognitive dysfunction in schizophrenic psychoses. Drug and psychological treatment choices].

Primarily from the perspective of psychopharmacology, schizophrenic symptomatology has recently been dichotomized into "plus" and "minus" symptoms, although the role of cognitive dysfunctions has been regarded as particularly important for the diagnosis since the time of Eugen Bleuler. Many studies show that schizophrenic patients suffer consistently from cognitive dysfunction. Among these, are impairments of attention and memory functions as well as executive functions such as planning and problem solving. These impairments are stable or progressive and often continue into the remission phase of schizophrenia and impair both social integration as well as occupational performance. In this overview, research results on cognitive dysfunction in patients with schizophrenic illnesses and their relation to psychosocial disabilities are described first. The therapeutic value and possible clinical-practice implications of atypical anti-psychotics and various cognitive therapy methods are then presented. Methodological weaknesses and open questions, both pharmacological and with regard to cognitive interventions, are discussed.

Antipsychotic Agents↗

Autism and Asperger's syndrome.

Knowledge about the spectrum of autistic disorders, including Asperger's syndrome, has grown significantly. Diagnoses can be made more reliably and there is better characterization of elements within the spectrum than ever before. A clearer picture of the cognitive limitations displayed by persons with conditions in the autistic spectrum is emerging. Deficits in manipulating abstract meanings, translating principles across contexts, and attending to contextual meanings can be seen in lower and higher functioning individuals. Links between "executive function," "theory of mind," and findings from functional imaging are becoming apparent. There are consistent indications that frontal and temporal regions play a crucial role in these disorders. Associations with specific genetic defects has been suggested, but methods capable of discovering the complex interplay of several genes will be needed before generalized conclusions can be reached.

Autistic Disorder↗