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PubMed2003

The effects of hormone therapy on cognition in breast cancer.

The use of hormonal therapies for the treatment of breast cancer is common, yet few studies have examined the possible cognitive effects. Several regions of the brain, important in memory and cognition, are rich in oestrogen receptors. As a result, the long-term use of anti-oestrogens may have potential consequences for cognition. This project aims to establish whether significant cognitive deficit exists in women receiving hormone therapy for breast cancer and to develop a cognitive package that is sensitive to the potential effects of oestrogen deficiency on cognition. Cognitive assessments measured a range of memory and attention functions in patient and control groups to identify whether cognitive impairment, if apparent, occurs at a widespread or function specific level. Ninety-four patients from the anastrozole, tamoxifen and combined (ATAC) trial and 35 non-cancer controls were assessed. Groups did not differ significantly in age or estimated full-scale intelligence. The patient group did not differ from controls on measures of working memory, attention and visual memory but was significantly impaired compared to the control group on measures of verbal memory (P=0.026) and processing speed (P=0.032). Cognitive performance in the patient group was not significantly related to length of time on trial or measures of psychological morbidity. As more and more hormonal agents are used in clinical trials of both adjuvant and preventive settings it is of vital importance that any potentially deleterious effects on cognitive function are measured adequately. Preliminary results from this study suggest that anti-oestrogen therapy may cause a specific deficit in verbal memory that corroborates the links between oestrogen levels and verbal memory often reported in studies of the cognitive benefits of hormone replacement therapy.

Affect↗

PubMed2006

Frontal anatomy and reaction time in Autism.

Widespread frontal lobe abnormalities, encompassing anatomy and function, are known to be implicated in Autistic Spectrum Disorders (ASD). The correlation between neurobiology and behaviour, however, is poorly understood in ASD. The aim of this study was to investigate frontal lobe anatomy and cognitive function in individuals with ASD, compared to control subjects. Thus, we assessed whole brain and frontal lobe parenchymal volume, and grey and white matter density differences in ASD, compared to control subjects, using high resolution T1-weighted magnetic resonance imaging (MRI). Furthermore, all subjects underwent a computerized reaction time task (RTT) for cognitive assessment. No differences in total parenchymal brain volume were observed, however, autistic individuals showed significantly smaller frontal lobe parenchymal volume (FLPV) and decreased white matter density, compared to control subjects. Error rates did not differ significantly between groups during the RTT, but ASD individuals responded significantly slower to target stimuli. Furthermore, reduced FLPV correlated positively with increased reaction time in individual with ASD. Decreased FLPV could be an indicator for abnormal brain development resulting in reduced processing speed in ASD.

Adult↗

PubMed2005

Impact of impaired glucose tolerance and type 2 diabetes on cognitive aging.

Type 2 diabetes is becoming increasingly common in most Westernized countries and it now occurs at a younger age. There are pathologies associated with diabetes, mostly systemic ones. However, a growing number of studies is also showing that diabetes is associated with impaired cognitive processes in older adults and hasten the progression to dementia. The most common cognitive deficits are decreases in processing speed and verbal memory; these may extend to other aspects of cognition with increasing age. The link between diabetes and cognitive decline is obscured by depression, hypertension, as well as cardio- and cerebrovascular diseases, all of which occur to varying degrees in diabetic patients. A few studies indicate that controlling blood glucose with anti-diabetic treatments may help prevent the cognitive decline in diabetic patients before they are 70 years old. After that age, diabetes appears to produce faster cognitive decline and may increase the occurrence of pathological changes associated with vascular dementia or Alzheimer's disease.

Aging↗

PubMed2007

Association between IL-8 cytokine and cognitive performance in an elderly general population--the MEMO-Study.

OBJECTIVES: To investigate the associations between circulating cytokines and specific neuropsychological domains of cognitive functioning (memory, processing speed and motor function) and general cognitive function (MMSE) in healthy elderly individuals. METHODS: In a cross-sectional study of 369 community dwelling elderly subjects, we examined the relationship between serum IL-1beta, sIL-4R, IL-6, IL-8, IL-10, IL-12 and TNF-alpha concentrations and cognitive performance using an extensive standardized and validated cognitive test battery assessing memory, word fluency, perceptual/cognitive speed, attention and executive functioning, and motor speed. RESULTS: Multivariate analysis adjusted for various confounders and Bonferroni correction for multiple comparisons demonstrated that increased serum concentrations of IL-8 were associated with poor performance in the memory and speed domains and in motor function. No significant associations were found between the remaining cytokines and domains of cognitive functioning. Global cognitive functioning, as measured with MMSE, was not associated with any cytokine. CONCLUSIONS: This study suggests an association between circulating IL-8 concentrations and cognitive dysfunction in the elderly. An interaction between this cytokine and glial cells may help explain the pathophysiological mechanisms leading to cognitive impairment in our study group.

Aged↗

PubMed2004

Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis.

fMRI and structural equation modeling (SEM) were used to study effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis (MS), while performing paced auditory serial addition test (PASAT), a sensitive task to reveal subtle cognitive impairments related to working memory and information speed processing. The path model used for SEM included bilateral connections between left and right BA 46, left and right BA 40, left and right anterior cingulate cortex (ACC), left BA 44 and left BA 40, right BA 44 and right BA 40, and unidirectional ipsilateral connections from BA 46 to BA 44, from ACC to BA 46, and from ACC to BA 44. Experimental data from the two groups fit accurately the working memory model, in patients [chi20(2) = 13, P = 0.877] as well as in controls [chi20(2) = 13.54, P = 0.853]. The omnibus test indicated a significant difference of model fits in patients and in controls [chi40(2) = 160.07, P < 0.0001]. Connectivity strengths from right BA 46 to left BA 46, from left ACC to left BA 46 were lower in patients than in controls, and higher from right ACC to right BA 46, from left to right and from right to left ACC (stacked model). Effective connectivity inside the working memory network appears altered in patients at the earliest stage of MS. Modulation of effective connectivity is present in patients inside the executive subsystems of working memory, and could be related to adaptive cognitive control processes that may limit the clinical manifestation of MS.

Acoustic Stimulation↗

PubMed2006

Neural correlates of cognitive efficiency.

Since its inception, experimental psychology has sought to account for individual differences in human performance. Some neuroimaging research, involving complex behavioral paradigms, has suggested that faster-performing individuals show greater neural activity than slower performers. Other research has suggested that faster-performing individuals show less neural activity than slower performers. To examine the neural basis of individual performance differences, we had participants perform a simple speeded-processing task during fMRI scanning. In some prefrontal cortical (PFC) brain regions, faster performers showed less cortical activity than slower performers while in other PFC and parietal regions they showed greater activity. Regional-causality analysis indicated that PFC exerted more influence over other brain regions for slower than for faster individuals. These results suggest that a critical determinant of individual performance differences is the efficiency of interactions between brain regions and that slower individuals may require more prefrontal executive control than faster individuals to perform successfully.

Adolescent↗

PubMed2006

Implicit learning deficits in dyslexic adults: an fMRI study.

It is assumed that several neuropsychological impairments characterize the cognitive profile of individuals with developmental dyslexia (DD). Phonological and visual processing are often impaired as well as auditory processing, attention, and information processing speed. Although reports in the literature on implicit learning abilities are contradictory, recent neurological and physiological data suggest that these abilities are deficient in individuals with DD. To evaluate implicit learning we administered a classical version of the serial reaction time task (SRTT) related to sequence learning. Using functional magnetic resonance imaging we investigated brain activation patterns associated with implicit learning deficits in 14 adults with DD matched with 14 normal readers. SRTT results indicated the absence of implicit learning in the DD group and different activations between groups mainly in SMA, inferior parietal areas and cerebellar lobule 6. These results can be interpreted in the light of the different capacities for the two groups to build an internal model to guide movements. Further, they explain DD individuals' difficulty in domains not directly related to reading ability.

Adult↗

PubMed2005

Persisting asymmetries of vision after right side lesions.

Visual neglect and extinction are well-known effects of lesions in the right hemisphere. This study shows that even with minor or no clinical signs of these deficits, and in the stable phase of recovery, asymmetric visual perception is common after right side lesions. Whole, partial and colour report experiments were used to estimate psychophysical parameters related to visual capacity and attentional weighting in 26 patients with stroke in the right side of the brain. The results were analyzed using Bundesen's Theory of Visual Attention (TVA [Bundesen, C. (1990). A theory of visual attention. Psychological Review, 97, 523-547]) including bootstrap estimation of the measurement error related to each test result [Habekost, T., & Bundesen, C. (2003). Patient assessment based on a theory of visual attention (TVA): Subtle deficits after a right frontal-subcortical lesion. Neuropsychologia, 41, 1171-1188]. Lesions were examined by MR scanning and analyzed statistically. Two main types of deficit were found. The first type was related to perception of unilateral displays, where most patients showed left side reductions of visual processing speed. This visual asymmetry correlated with injury to the putamen and surrounding white matter. The second deficit type occurred with bilateral displays, which increased the visual asymmetry (extinction effect) for most patients with large cortico-subcortical lesions, but rarely for patients with focal lesions. However, in a single case with pulvinar damage, visual asymmetry occurred selectively with bilateral stimulation. Overall, the study provided an overview of the cognitive structure and lesion anatomy of subtle visual asymmetries after right side stroke.

Adult↗

PubMed2006

Neurocognitive consequences of cigarette smoking in young adults--a comparison with pre-drug performance.

The present study examined effects of current and past regular cigarette smoking in young adult subjects. One hundred and twelve 17-21-year-old subjects, assessed since infancy, were evaluated using a battery of neurocognitive tests for which commensurate measures were obtained at 9-12 years of age, prior to the initiation of regular smoking. Smokers, determined by urinalysis and self-report, were categorized as heavy (>9 cigarettes per day) and light (<9 cigarettes per day) current smokers and former smokers, the latter having smoked cigarettes regularly in the past but not for at least 6 months. A third of the subjects were currently smoking cigarettes regularly with half of these being heavy smokers. Among former smokers, the average duration of smoking was slightly less than 2 years. Overall IQ, memory, processing speed, vocabulary, attention and abstract reasoning were the primary outcomes with comparisons being made between each of the three user groups and a control group who never smoked regularly. After accounting for potentially confounding factors including clinical assessment, marihuana use and pre-drug performance in the relevant cognitive domain, current regular smokers did significantly worse than non-smokers in a variety of cognitive areas predicated upon verbal/auditory competence including receptive and expressive vocabulary, oral arithmetic, and auditory memory. This impact of current smoking appears to behave in a dose-response and duration-related fashion. In contrast, former smokers differed from the non-smokers only in the arithmetic task. These results suggest that regular smoking during early adulthood is associated with cognitive impairments in selected domains and that these deficits may be reversed upon cessation. Together, the findings add to the body of evidence to be used in persuading adolescents and young adults against the initiation of smoking and, if currently smoking, the advantages of stopping.

Adolescent↗

PubMed2004

Depression and the 25-item National Eye Institute Visual Function Questionnaire in older adults.

PURPOSE: To examine the impact of depression in older adults on responses to the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) independent of demographics, vision, and general health. DESIGN: Cross-sectional. PARTICIPANTS: We took the opportunity of an ongoing study on older drivers to address the specific aim stated above. The recruitment population consisted of 6342 older adults (> or =60 years) who were licensed drivers residing in Birmingham, Alabama; who had been involved in a crash in the prior year, as identified by Alabama Department of Public Safety records; and whose phone numbers could be located. Additional eligibility criteria were visual acuity impairment, slowed visual processing speed, or both, and a Mini-Mental State Examination score of > or =23. Persons in the recruitment population who met these eligibility criteria and agreed to enroll in a study on driver safety (purpose of the main study) numbered 403. METHODS: The following questionnaires were interviewer administered in person and scored per standard procedures: the NEI VFQ-25, the Center for Epidemiological Studies Depression Scale (CES-D), a general health questionnaire, and a review of demographic information. Depressed persons were defined as those with CES-D scores of > or =16. There were complete data on 397 persons. MAIN OUTCOME MEASURE: Reduced score on the NEI VFQ-25 (defined by a score of <87.5) on the total questionnaire and 12 subscales. RESULTS: After adjusting for demographics, vision, mental status, and general health, depression was significantly associated with a reduced NEI VFQ-25 score for total score and the subscales of distance vision, peripheral vision, role difficulties, dependencies, and mental health. Odds ratio point estimates in these adjusted associations ranged from 2.9 to 4.6. CONCLUSIONS: The results imply that older persons who are depressed may have reduced scores on the NEI VFQ-25 independent of the impact of vision problems. Depression in the elderly could be influencing their self-perception of the burden of eye disease and treatment effectiveness in clinical and epidemiologic studies.

Aged↗

PubMed2006

Everyday cognitive function after craniopharyngioma in childhood.

Despite clinical impressions that cognitive complaints are prominent in patients with a history of craniopharyngioma, formal neuropsychologic documentation is inconsistent. This study assessed everyday cognitive complaints and neuropsychologic test performance to evaluate the prevalence of problems and the relationship of these domains to one another in patients treated for craniopharyngioma in childhood or adolescence. Ten patients treated for craniopharyngioma completed measures of everyday cognitive function (Cognitive Failures Questionnaire, Rivermead Behavioural Memory Test) and a battery of standard neuropsychologic tests. The prevalence of problems was ascertained for each measure. Most patients demonstrated significant deficits in everyday memory (Cognitive Failures Questionnaire, 9/10 patients; Rivermead Behavioural Memory Test, 7/10 patients). Scores were within normal limits, however, for intelligence quotient, achievement, attention, verbal memory, and spatial working memory. Processing speed was slow (5/10 patients). Spatial working memory predicted Cognitive Failures Questionnaire (P < 0.07), as did somatic symptoms from the Beck Depression Inventory (P < 0.01), but these associations appeared independent. Adolescents and young adults with treated craniopharyngioma experience deficits in everyday cognitive functions, many involving memory, that are not easily detected by standard neuropsychologic testing. The extent of self-rated cognitive problems is related to spatial working memory and somatic concerns.

Activities of Daily Living↗

PubMed2026

Potential contribution of the microbiota-gut-brain axis to doxorubicin-associated cognitive impairment: Mechanisms, evidence, and therapeutic opportunities.

Chemotherapy-induced cognitive impairment (CICI), often termed chemobrain, is a clinically important complication of cancer treatment that can affect memory, attention, executive function, and processing speed during and after therapy. Doxorubicin is of particular mechanistic interest because brain parenchymal exposure is limited, yet preclinical studies consistently identify neuroinflammatory, oxidative, vascular, and synaptic abnormalities after treatment. This critical narrative review evaluates whether intestinal injury and disruption of the microbiota-gut-brain axis may contribute to these central effects. Preclinical evidence indicates that doxorubicin can alter microbial community structure, injure the intestinal barrier, modify SCFA-associated taxa or predicted functions, alter selected metabolite profiles, and promote systemic inflammatory and metabolic signaling. These peripheral changes could interact with brain endothelial cells, glia, mitochondria, hippocampal neurogenesis, and synaptic-plasticity pathways. However, the proposed doxorubicin-gut-brain pathway remains a predominantly preclinical and incompletely tested framework. No longitudinal human study has yet established, within the same patients, the temporal sequence linking doxorubicin exposure, microbiome or metabolome changes, systemic inflammation, and objective cognitive outcomes. Existing animal studies also vary in dose, regimen, tumor context, sampling time, microbiome methodology, and control of behavioral or microbiological confounders, while causal rescue experiments remain limited. Key priorities are therefore longitudinal human cohorts with pretreatment baselines and repeated multi-omics and cognitive assessments; animal studies that test temporal precedence and causal rescue or pathway blockade in the same model; mediation analyses that determine whether microbial or metabolic changes lie between treatment and cognitive dysfunction; and mechanism-informed clinical trials that demonstrate target engagement, cognitive benefit, oncology safety, and preservation of antitumor efficacy. Microbiome-directed interventions are promising but remain investigational for doxorubicin-associated CICI.

blood–brain barrier↗

PubMed2004

A comparison of two novel antipsychotics in first episode non-affective psychosis: one-year outcome on symptoms, motor side effects and cognition.

The main objective of this study was to compare 1-year outcome on symptoms, extrapyramidal side effects (EPS) , positive and negative symptoms, and domains of cognition in first episode psychosis (FEP) patients. Drug-naive FEP patients, who were similar on a number of characteristics likely to affect outcome, were treated with only one antipsychotic (risperidone or olanzapine) for at least 1 year and compared at baseline and after 1 year of treatment. Differences in outcome were assessed using an analysis of co-variance with change scores between initial assessment and after 1 year of treatment on levels of psychotic, disorganization and psychomotor poverty symptoms, EPS (parkinsonism, akathesia and dyskineisa) and domains of cognition as the dependent variable, respective baseline scores as covariates, and drug group as the independent variable. While patients in both groups showed substantial improvement, there were no significant differences in the magnitude of change in reality distortion, disorganization and psychomotor poverty symptoms. Trends in change in EPS favouring olanzapine and on some domains of cognition (processing speed and executive functions) favouring risperidone failed to reach statistical significance. The failure to confirm previous claims of greater improvement on either risperidone or olanzapine in patients with a first episode of psychosis may be the result of methodological bias introduced by unequal dosing between the two drugs or the use of chronically ill and treatment-refractory patients in previous studies.

Adolescent↗

PubMed2005

The neuropsychology of borderline personality disorder: a meta-analysis and review.

The neuropsychological profile of borderline personality disorder (BPD) is unclear. Past investigations have produced seemingly inconsistent results concerning precisely what neuropsychological deficits characterize the patient with BPD. A meta-analysis of 10 studies was conducted comparing BPD and healthy comparison groups on selected neuropsychological measures comprising six domains of functioning: attention, cognitive flexibility, learning and memory, planning, speeded processing, and visuospatial abilities. BPD participants performed more poorly than controls across all neuropsychological domains, with mean effect sizes (Cohen's d) ranging from -0.29 for cognitive flexibility to -1.43 for planning. The results suggest that persons with BPD perform more poorly than healthy comparison groups in multiple neurocognitive domains and that these deficits may be more strongly lateralized to the right hemisphere. Although neuropsychological testing appears to be sensitive to the neurocognitive deficits of BPD, the clinical utility of these results is limited. Implications of these findings for future neurocognitive investigations of BPD are discussed.

Borderline Personality Disorder↗

PubMed2006

State-dependent implicit learning deficit in schizophrenia: evidence from 20-month follow-up.

Previous research has confirmed stable explicit memory deficits in schizophrenia across disease states. However, little is known about the implicit learning capabilities of individuals with schizophrenia across the course of illness. The current study assessed procedural learning in 19 schizophrenia subjects (DSM-IV criteria) and 19 matched controls using the Serial Reaction-Time Task (SRTT). The severity of negative, positive and disorganized symptoms was assessed using the Scales for the Assessment of Positive and Negative Symptoms. A sub-sample of 11 schizophrenia subjects and 11 controls was reassessed 20 months later when symptoms in the schizophrenia subjects had largely remitted. Schizophrenia subjects were severely impaired on sequence-specific procedural learning during an acute episode. This deficit could not be explained by a general memory or processing speed impairment. Impaired implicit learning scores were significantly related to higher ratings of disorganized symptoms. However, 20 months later, when acute symptoms had remitted, the performance of the schizophrenia subjects on procedural learning had normalized. Our findings might share a conceptual overlap with previous reports of a reduced ability of schizophrenia subjects during an acute episode to adapt ongoing perceptual and behavioral programs to previously experienced regularities in their environment.

Adult↗

PubMed2005

Histories of childhood maltreatment in schizophrenia: relationships with premorbid functioning, symptomatology, and cognitive deficits.

A number of studies have demonstrated an increased rate of histories of childhood maltreatment among adults with serious mental illness. The present investigation documented the presence of childhood maltreatment in a sample of 40 psychiatric inpatients with schizophrenia spectrum disorders. The type (neglect, physical abuse, sexual abuse), duration, and severity of childhood maltreatment was examined along with measures of premorbid functioning, current symptomatology, and cognitive functioning. Participants with histories of maltreatment were significantly more likely to have poorer peer relationships in childhood, more difficulty in school, an earlier age at first hospitalization, more previous hospitalizations, elevated symptoms of anxiety, depression, and suicidality on the Brief Psychiatric Rating Scale (BPRS), and more impaired performance on a task of visual-perceptual organization. Severity and frequency of childhood maltreatment were both positively correlated with hallucinations and delusions on the BPRS. Linear trend analysis indicated a pattern of more severe impairment as the number of types of maltreatment increased. No relationships were found between maltreatment and measures of executive functioning, verbal fluency, or verbal processing speed. A history of childhood maltreatment appears to be a significant determinant of premorbid functioning, illness-related symptom expression, and specific forms of cognitive dysfunction.

Adult↗

PubMed2005

Decision-making capacity for research participation among individuals in the CATIE schizophrenia trial.

OBJECTIVE: Uncertainty regarding the degree to which persons with schizophrenia may lack decision-making capacity, and what the predictors of capacity may be led us to examine the relationship between psychopathology, neurocognitive functioning, and decision-making capacity in a large sample of persons with schizophrenia at entry into a clinical trial. METHOD: In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial, a clinical trial sponsored by the National Institute of Mental Health designed to compare the effectiveness of antipsychotic drugs, subjects were administered the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) and had to demonstrate adequate decision-making capacity before randomization. The MacCAT-CR, the Positive and Negative Syndrome Scale (PANSS), and an extensive neurocognitive battery were completed for 1447 study participants. RESULTS: The neurocognitive composite score and all 5 neurocognitive subscores (verbal memory, vigilance, processing speed, reasoning, and working memory) were positive correlates of the MacCAT-CR understanding, appreciation, and reasoning scales at baseline. Higher levels of negative symptoms, but not positive symptoms, were inversely correlated with these three MacCAT-CR scales. Linear regression models of all three MacCAT-CR scales identified working memory as a predictor; negative symptoms made a small contribution to the understanding and appreciation scores. CONCLUSIONS: Negative symptoms and aspects of neurocognitive functioning were correlated with decision-making capacity in this large sample of moderately ill subjects with schizophrenia. In multiple regression models predicting performance on the MacCAT-CR scales, working memory was the only consistent predictor of the components of decision-making capacity. Individuals with schizophrenia who have prominent cognitive dysfunction, especially memory impairment, may warrant particular attention when participating in research.

Adolescent↗

PubMed2006

Impaired error monitoring contributes to face recognition deficit in schizophrenia patients.

BACKGROUND: It has been proposed that social and cognitive deficits in schizophrenia may result from impaired error monitoring. OBJECTIVE: We tested the hypothesis that among schizophrenia patients, impaired error monitoring contributes to poor face recognition, an important social skill. METHODS: 79 schizophrenia patients and 57 healthy individuals were administered a computerized face recognition test which allowed collection of accuracy and latency performance parameters. Error monitoring was assessed by analyzing reaction times for correct (RTC) and incorrect (RTI) responses. Tests of working memory (WM) and processing speed were also administered. RESULTS: RTI was longer than RTC in patients and controls and did not differ between the groups. RTC was significantly longer in patients than controls. Error monitoring effort, calculated by dividing the difference between RTI and RTC by the sum of RTC and RTI, was significantly smaller in patients than controls. A regression model with face recognition performance as dependent variable showed independent contributions of error monitoring effort, spatial working memory and group (patient/healthy) to test performance and explained 26.1% of the variance. CONCLUSION: Error monitoring function influences face recognition accuracy and is impaired in schizophrenia. Impairments in error monitoring, and spatial WM contribute to face recognition deficits in schizophrenia.

Adult↗