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PubMed1994

Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study.

BACKGROUND AND PURPOSE: Ventricular enlargement and white matter lesions are frequent findings on cerebral magnetic resonance imaging scans of elderly subjects. In demented subjects they seem related to the severity of the dementia, but in nondemented subjects their clinical significance is less clear. We investigated the relation of size of the lateral ventricles and white matter lesions with cognitive function in a population-based random sample of nondemented elderly persons. METHODS: The study population consisted of 90 subjects, aged 65 to 84 years, who were randomly selected from the cohort of the Rotterdam Study, and who were not demented. The presence of white matter lesions and the ventricle-to-brain ratio were assessed on magnetic resonance scans. Participants were tested with a neuropsychological battery that covered a broad range of cognitive functions. RESULTS: Ventricular enlargement and white matter lesions were both and independently associated with poorer performance on all tests. After adjustment for age and sex, ventricular enlargement was significantly associated with worse scores on tests assessing global cognitive function (Mini-Mental State Examination, P = .02; Groninger Intelligence Test, P = .01), memory (Word List Learning delayed recall, P = .03), and executive control functions (Stroop part II, P = .02; Trial Making Test B, P < .01); for white matter lesions the differences were significant for tests measuring executive control functions and mental speed (Trail Making Test A and B, P = .01 and P < .01, respectively; verbal fluency, P = .01), and memory (Word List Learning delayed recall, P = .04). CONCLUSIONS: This study suggests that white matter lesions are primarily related to impairment of subcorticofrontal functions, whereas enlargement of the lateral ventricles is associated with disturbances of cortical functions as well.

Age Factors↗
PubMed2002

Fluoxetine's effects on cognitive performance in patients with traumatic brain injury.

OBJECTIVE: There are preclinical data showing that fluoxetine stimulated expression of Brain Derived Neurotrophic Factor (BDNF) and its specific tyrosine kinase receptor, and caused neuritic elongation and increased dendritic branching density of CA3 hippocampal pyramidal cell neurons in rodents. The latter effect of fluoxetine has been referred to as neuronal remodeling. In view of this preclinical data, we wondered if specific cognitive measures could serve as novel therapeutic targets for fluoxetine in head-injured patients. Theoretically, fluoxetine-induced "neuronal remodeling" might improve cognition, independently of a primary effect on mood. METHOD: In an open-label pilot investigation, fluoxetine hydrochloride (Prozac; 20-60 mg/day) was administered to a heterogeneous group of five head-injured patients with either no or moderate depression for a period of eight months. These patients had no histories of prior treatment with antidepressant medications. They were administered cognitive and memory tests at baseline and after eight months of treatment on fluoxetine. RESULTS: The preliminary results showed that fluoxetine improved mood, in addition to improving performance on the Trail Making Test Part A, an attentional-motor speed task, and the letter-number sequencing subtest of the WAIS-III, a measure reflecting "working memory." CONCLUSIONS: Although fluoxetine had beneficial effects on some measures of cognition, more work is needed to connect these improvements with neuronal remodeling.

Aged↗
PubMed2006

Neuropsychological correlates of error negativity and positivity in schizophrenia patients.

The purpose of the present paper was to determine error-monitoring ability and its relationship with executive function in patients with schizophrenia. In order to evaluate error-monitoring ability, the error negativity (Ne) and error positivity (Pe) were measured using the Stroop task. The correct-related negativity (CRN) and positivity (Pc) were also measured. In addition, neuropsychological tests were administered in order to evaluate executive function. The patients with schizophrenia had significantly reduced Ne and augmented CRN amplitudes, but the Pe and Pc amplitudes of the patients were comparable to those of the controls. In addition, the Ne amplitude, measured at Fcz was positively correlated with the Trail Making Test (TMT), part B response time, and the categories achieved on the Wisconsin Card Sorting Test (WCST) in patients with schizophrenia. No significant correlations were found between Ne amplitude and performance on the neuropsychological tests in the controls. And no associations were detected between CRN, Pe, Pc amplitudes and neuropsychological performance, in either the patients with schizophrenia or the controls. Reduced Ne amplitudes and augmented CRN amplitudes in patients with schizophrenia suggest the dysfunctional behavior-monitoring system in these patients. The functional significances of Ne and Pe are discussed.

Adult↗
PubMed2003

Behavioral Dyscontrol Scale deficits among traumatic brain injury patients, part II: Comparison to other measures of executive functioning.

The clinical utility of the Behavioral Dyscontrol Scale (BDS) was compared to that of verbal fluency, the Trail Making Test, and the Stroop Color-Word Test, as well as measures of processing speed/cognitive efficiency and manual dexterity. The ability of these measures to classify 49 TBI patients into frontal versus nonfrontal and mild to moderate versus severe groups was examined. The results showed that the Fluid Intelligence Factor of the BDS improved classifications above and beyond traditional executive measures, but was particularly successful at classifying patients who sustained mild injuries. In contrast, traditional executive instruments were successful at lesion location classifications only among the patients with severe injuries. Severity classifications were successful both for traditional measures of processing speed/cognitive efficiency and for the Motor Programming Factor of the BDS, but only among patients with nonfrontal injuries. These results demonstrate that severity of injury may be an important moderator of tests' sensitivity to frontal lobe involvement.

Adult↗
PubMed1999

A simple test of central processing speed: an extension of the Short Blessed Test.

OBJECTIVE: To evaluate the efficacy and reliability of a simple measure of central processing speed: the time to recite the months of the year in reverse order, from the Short Blessed Test of Orientation, Concentration, and Memory (SBT). DESIGN: Cross-sectional and longitudinal designs were used to establish validity and test-retest reliability. SETTING: Participants' homes and by telephone interview. PARTICIPANTS: An age-stratified sample of 120 community-dwelling women, aged 67-94, randomly selected from Medicare recipients of the St. Louis Metropolitan Statistical Area. MEASUREMENTS: Dependent variables were the SBT, the Trail Making Test, computer-generated simple and choice reaction time, and time to say the months of the year backward (TMYB). The independent variable was age. RESULTS: Significant Pearson product-moment correlations were obtained for Trail Making and TMYB with a simple and choice reaction time after controlling for age and cognitive status. An exponential relationship was observed between age and TMYB, expressed both cross-sectionally and as rate of change. Test-retest reliability for TMYB was 0.90. CONCLUSIONS: TMYB is a valid and reliable measure of central processing speed that compares favorably to the more elaborate and time-consuming Trail Making B test. Because of its simplicity and ease of administration, this test provides the clinician with a practical measure of central processing speed. TMYB extends the utility of the widely used Short Blessed Test by measuring this additional and important domain of brain function.

Age Factors↗
PubMed2006

Neuropsychological profile of adult patients with Niemann-Pick C1 (NPC1) mutations.

Niemann-Pick type C disease is a fatal neurovisceral disorder linked to dysregulation in cholesterol processing. A medication for this disease is currently being tested in clinical trials. However, there is a lack of information on neuropsychological testing parameters for this disease. One aim of this pilot study was to evaluate a test battery that could be used to assess cognitive deficits in different stages of the disease. A second aim was to determine whether specific functional deficits are associated with certain disease stages. Eight men and two women (19-40 years of age) harbouring mutations in the gene coding for the cholesterol trafficking protein NPC1 were put through the same test battery independently of their disease stage. The external staging criterion was based on a five-step clinical scale. Trail Making tests A & B and verbal fluency were sensitive indicators at early stages of NPC. Corsi Block-Tapping, Mini Mental Status, Find Similarities and Clock Drawing showed abnormal results in patients with advanced disease. The Grooved Pegboard, Trail Making and Mosaic tests were unsuitable in advanced disease due to impaired fine motor skills. We observed that visuospatial working memory was less affected by the neurodegenerative process than verbal working memory. The series of tests used here could be supplemented by the severe impairment battery and Raven matrices tests for patients with advanced disease.

Adult↗
PubMed2000

Age-associated changes in cognitive function in highly educated adults: emerging myths and realities.

The effects of education and continued intellectual engagement on age-associated cognitive change were investigated in a sample of 102 members of the professional and college communities in the metro Atlanta Georgia area (ages 30-76). All participants were administered a 60-minute battery that measured different aspects of memory, intelligence and cognitive performance. Age-associated declines in performance were detected on the digit symbol measure of intelligence. Conversely, positive but non-significant trends were detected on the picture completion, arithmetic and similarities subtests. Age effects were also noted on some measures of the Wisconsin Card Sorting Test and both versions of the Trail Making Test. The findings suggest that at least among the highly educated, certain cognitive abilities may receive some degree of amelioration as a consequence of continued intellectual engagement. However, the effects may be associated more with compensation rather than protection against the effects of ageing.

Adult↗
PubMedDate not supplied

The effect of fatigue, sleep deprivation and onerous working hours on the physical and mental wellbeing of pre-registration house officers.

The potential deleterious effects of doctors' long and arduous shifts have received relatively scant attention. This study addressed the effect of a 32 h on-call shift on 16 pre-registration medical house officers in St. James's Hospital, Dublin. We assessed 5 psychological parameters (Tension-Anxiety, Depression-Dejection, Vigour-Activity, Fatigue-Inertia and Confusion-Bewilderment) as well as 5 simple tests of alertness and concentration both pre- and post-call. The doctors were randomly assigned to be tested either pre- or post-call. On average the doctors got 4.5 hours sleep during a 32 h shift. This long shift had an adverse effect on all the psychological parameters (p < 0.05) except Depression-Dejection. The total mood disturbance score, which has been shown to correlate well with general psychological well-being, deteriorated significantly after the 32 h shift, p < 0.005. Two of the simple tests of alertness and concentration (Trail-making test and Stroop Color-Word test) also showed a significant fall-off in performance with sleep deprivation, p < 0.05, although the remaining tests (Delayed Story Recall, Critical Flicker Fusion and Three Minute Grammatical Reasoning Test) were not significantly impaired by the 32 h shift. This study shows that prolonged periods of duty without sleep adversely affect junior doctors, both in their psychological well-being and in their ability to carry out simple tasks.

Adult↗
PubMed1994

Cognition in humans and the borderline to dementia.

From a psychometric point of view, cognitive performance in humans has to be examined as a multidimensional quantitative construct. Models of memory and intelligence may serve to describe the complex interactions of cognitive functioning. Based on memory research and reliable psychometric methods a three-dimensional model including "Primary Memory", "Secondary Memory" and a "Speed factor" is proposed. Using models of performance factors. "Cognitive Speed" is demonstrated as a marker variable of "Fluid Intelligence". It is shown, that "Cognitive Speed" is clearly age-associated and constitutes a key function for other cognitive domains and for activities-of-daily-living. Furthermore "Cognitive Speed" is a crucial cognitive domain to separate normal from pathological aging. As an example to assess "Cognitive Speed", the Zahlen-Verbindungs-Test G (1), a modified trail-making test, is discussed to diagnose beginning and ongoing dementias.

Aged↗
PubMed1995

Habituation of auditory N100 correlates with amygdaloid volumes and frontal functions in age-associated memory impairment.

We studied the habituation of auditory N100 responses in subjects with age-associated memory impairment (AAMI) and in healthy age-matched volunteers. The findings were correlated with volumes of the amygdala, hippocampus, and frontal lobe measured by magnetic resonance imaging (MRI), as well as with subjects' performance on tests assessing frontal lobe functions and memory. Habituation of N100 did not differ across AAMI subjects and controls. However, in AAMI subjects there was a significant correlation between habituation of N100 and volumes of the amygdala; the more reduced habituation, the smaller volume. In addition, decline in habituation of N100 correlated with impaired performance on a visual memory test (Heaton Visual memory test (Heaton Visual Retention Test; r = 0.77; p < 0.001) and impairment on tests assessing frontal functions (Verbal Fluency, Trail Making Test, and Stroop). Habituation of N100 was not related to age or sex. To our knowledge this is the first study to demonstrate a relationship between habituation of evoked responses, MRI volumetric measures, and performance on psychometric tests. The results suggest that impaired memory and frontal lobe functions in AAMI subjects may be associated with poor habituation of N100. Since habituation reflects focusing of attention to relevant features of stimuli, impairment of this mechanism and subsequent defective memory trace formation may contribute to the observed deficits on memory tests.

Aged↗
PubMedDate not supplied

Results from the European multicenter study on lead neurotoxicity in children: implications for risk assessment.

In order to improve dose-response information on neurobehavioral effects of environmental lead exposure in children, the World Health Organization, Regional Office for Europe (WHO/EURO), in collaboration with the Commission of the European Communities, initiated this international study which was planned, executed and evaluated between 1984 and 1989. Eight groups from eight European countries (Bulgaria, Denmark, Greece, Hungary, Italy, Roumania, W. Germany and Yugoslavia) took part. A common study protocol with inherent quality assurance elements was developed to achieve comparability. Blood-lead concentrations (PbB) were the main markers of exposure. The WISC (4 subtests) for psychometric intelligence, the Bender Gestalt test (GFT version) and the Trail-Making test for visual-motor integration, the Vienna Reaction Device and a delayed RT task for reaction performance, and the Needleman scales for behavior ratings served as behavioral endpoints. All individual studies taken together represent a sample size of 1879 school-age children and cover a PbB range from below 5 to about 60 micrograms/100 ml. Overall statistical evaluation of outcome was done by multiple regression analysis using a uniform confounder model. The strongest and most consistent effects occurred for the Bender Gestalt test (GFT version) and for serial choice reaction performance (Vienna Device). The degree of association with PbB was significant for these variables, although the contribution of PbB to the observed variance never exceeded 0.8%. Psychometric intelligence was also negatively affected, although the consistency of outcome between studies was poor, and the association with PbB only borderline. An effort towards risk assessment was made by calculating the proportion of children at risk, using the observed regression coefficients as well as means and standard deviations.

Child↗
PubMed2004

A neuropsychological investigation of male premutation carriers of fragile X syndrome.

It is currently thought that fragile X syndrome (FraX; the most common inherited form of learning disability) results from having more than 200 cytosine-guanine-guanine (CGG) trinucleotide repeats, with consequent methylation of the fragile X mental retardation (FMR1) gene and loss of FMR1 protein (FMRP). It was also considered that premutation carriers (with 55-200 CGG repeats) are unaffected, although a tremor/ataxia syndrome has recently been described in older adult male carriers. We reported that premutation expansion of CGG trinucleotide repeats affects brain anatomy, which, together with other studies, indicates that the molecular model for FraX needs modification. However, there are few studies on the cognitive ability of adult male premutation carriers. Thus, we selected 20 male premutation carriers on the basis of their genetic phenotype, and compared them to 20 male controls matched on age, IQ and handedness. We investigated intellectual functioning, executive function, memory, attention, visual and spatial perception, and language and pragmatics. The premutation carriers had significant impairments on tests of executive function (Verbal Fluency, Trail Making Test and Tower of London) and memory (Names sub-test of the Doors and People, Verbal Paired Associates Immediate Recall and Visual Paired Associates Delayed Recall sub-tests of the WMS-R, and Category Fluency Test for natural kinds). We therefore suggest that CGG trinucleotide repeats in the premutation range affect specific neuronal circuits that are concordant with specific neuropsychological deficits; and that these deficits reflect an emerging neuropsychological phenotype of premutation FraX.

Adult↗
PubMed2006

IPA survey of brief cognitive screening instruments.

BACKGROUND AND OBJECTIVES: Cognitive screening is a "first step" in detecting dementia and other neuropsychiatric syndromes and hence represents an important public health and clinical initiative. A plethora of cognitive screening instruments has been advocated in recent years, but the extent to which these instruments are used or their effectiveness is not well known. An International Psychogeriatric Association (IPA) survey was designed to determine which cognitive screening instruments were used most frequently by clinicians with special expertise in the neuropsychiatric aspects of old age and also to determine the ones considered most useful by these specialists. METHOD: Under the auspices of the IPA, the survey was mailed in the fall of 2004 to all IPA members as well as members of the American and Canadian Associations of Geriatric Psychiatry. The survey inquired about demographic information, the frequency of use of cognitive screening instruments, and the value attributed to the cognitive screening instruments. Participants also had an opportunity to provide written commentary. RESULTS: A total of 334 completed surveys were processed. The majority of respondents were geriatric psychiatrists (58%). Of the 20 different instruments that were listed on the survey, only six were selected as "routinely" or "often used" by the survey respondents. These instruments in declining order were: (1) the Folstein Mini-mental State Examination; (2) the Clock Drawing Test; (3) Delayed Word Recall; (4) the Verbal Fluency Test; (5) Similarities; and (6) the Trail Making Test. "Effectiveness" and "ease of administration" were the test characteristics most highly predictive of frequency of use. Open-ended comments highlighted patient factors that continue to provide challenges, including ethnicity/culture, language, education/literacy, and sensory impairment. Respondents concluded that "no single test is adequate." CONCLUSIONS: Psychogeriatricians worldwide routinely use a relatively small number of brief cognitive screening instruments. Further evaluation is necessary as the need increases for cognitive screening guidelines that inform public health initiatives related to dementia and neuropsychiatric syndromes.

Adult↗
PubMed2004

Effects of diffuse axonal injury on speed of information processing following severe traumatic brain injury.

To test the hypothesis that slowed information processing in traumatic brain injury is related to diffuse axonal injury (DAI), the authors compared 10 patients with predominant DAI (diffuse group) and minimal DAI (mixed injury group) on the Symbol Digit Modalities Test, simple and choice reaction time, Trail Making Tests A and B, and the Stroop Neuropsychological Screening Test. The diffuse group was slower than the mixed injury and control groups on basic speed of processing tasks. This difference was not apparent on complex speeded tasks once basic speed of processing was controlled for. The diffuse group's slower speed of processing was not accounted for by differences in injury severity, age, or time postinjury. The diffuse group showed greater recovery over time.

Adolescent↗
PubMedDate not supplied

Outcomes in TBI with violent versus nonviolent etiology in a predominantly rural setting.

OBJECTIVE: To evaluate differences in outcome in persons with violent versus nonviolent traumatic brain injury (TBI) etiology. DESIGN: Two-group (violent vs nonviolent) 1-year follow-up study. SETTING: Midwestern medical center TBI Model System serving a predominantly rural catchment area. PARTICIPANTS: Forty-five (n = 19 violent TBI etiology; n = 26 nonviolent TBI etiology) inpatients with primary diagnosis of TBI followed up as outpatients 1 year after injury. MAIN OUTCOME MEASURES: Substance use, income source, employment status, Wechsler Adult Intelligence Scale--Revised (abbreviated version), Logical Memory I and II from the Wechsler Memory Scale--Revised, Wide Range Achievement Test--Third Edition Reading subtest, Trail-Making Tests A and B, Rey Auditory Verbal Learning Test, Community Integration Questionnaire, Neurobehavioral Functioning Inventory. RESULTS: Members of the violent group were more likely to be men, of a racial minority, unemployed, and have low income. Substance abuse was common among both groups prior to injury, with significant declines at 1 year. Follow-up also revealed significant group differences in verbal intelligence, social integration, productivity, and source of income, but nonsignificant difference in employment. In all comparisons, more favorable outcomes were found for the nonviolent group. CONCLUSIONS: Persons with violent injury etiology have poorer premorbid functioning and are likely to have less favorable outcomes than the general population with TBI. Therefore, persons with violent TBI etiology may require more intensive aftercare programming to promote improved rehabilitation outcomes.

Adolescent↗
PubMed2005

Persistent cognitive dysfunction in patients with obsessive-compulsive disorder: a naturalistic study.

The purpose of the present study was to investigate the changes in the cognitive dysfunctions of patients with obsessive-compulsive disorder (OCD) over a 1-year period of pharmacological treatment. Twenty-one OCD patients and 20 normal subjects underwent neuropsychological tests and clinical evaluations on three separate occasions (baseline, 4 months, and 1 year after the start of medications). OCD patients continued to show significant impairments in the following cognitive measures compared with the normal controls: accuracy of immediate and delayed recall on the Rey-Osterrieth complex figure tests, the numbers of responses on the category fluency test, the response time on the trail making test--part A, and the number of perseverative response and perseverative errors on the Wisconsin card sorting test. The findings in this study suggested that impaired performance on cognitive domains, such as visuospatial memory and verbal fluency may underline the pathology of OCD.

Adult↗
PubMed1996

Negative symptoms, cognitive dysfunction, tardive akathisia and tardive dyskinesia.

This study examined the relationship of neuropsychological deficits and negative symptoms with tardive akathisia in chronic schizophrenic patients. Consecutive volunteers (n = 100) were recruited from Community Health Centres with a DSM-III-R diagnosis of schizophrenic disorder, chronic and on stable medication. Subjects were subgrouped into tardive akathisia (TA), tardive dyskinesia (TD) and control groups using four sets of criteria. Detailed single examinations were performed using the following measures: sociodemographic, illness-related and treatment-related variables, Negative Symptom Rating Scale (NSRS), Abnormal Involuntary Movement Scale (AIMS), Rating Scale for Extrapyramidal Side-Effects (EPSE), Akathisia Rating Scale, Barnes Akathisia Rating Scale, and a brief neuropsychological test battery. Group comparisons and logistic regression analyses were performed in order to test the significance of findings. TA ratings showed a significant association with NSRS subscale scores, and with some neuropsychological test scores (Symbol Digits Modalities Test, and to a lesser extent Trail Making Test and Finger Tapping Test). TD scores showed a consistent association with age, and a less consistent association with gender, and their association with NSRS subscale scores and neuropsychological dysfunction was positive but less significant. Higher EPSE scores predicted TA and limb truncal (LT) dyskinesia. In conclusion, TA showed a more significant association with some clinical indices of organic brain dysfunction than the oral-lingual-buccal-facial dyskinetic syndrome. Prospective studies are necessary to determine whether organicity is a vulnerability factor for TA. Both our data and the published literature suggest that the movement disorder seen in TA and TD is but one feature of complex syndromes that include motor and cognitive features.

Adult↗
PubMed2006

Influence of APOE polymorphism on cognitive and behavioural outcome in moderate and severe traumatic brain injury.

AIM: To analyse the influence of apolipoprotein (APOE) epsilon4 status on the cognitive and behavioural functions usually impaired after moderate and severe traumatic brain injury (TBI). METHODS: In all, 77 patients with TBI selected from 140 consecutive admissions were genotyped for APOE. Each patient was subjected to neuropsychological and neurobehavioural assessment at least 6 months after injury. RESULTS: Performance of participants carrying the epsilon4 allele was notably worse on verbal memory (Auditory Verbal Learning Test), motor speed, fine motor coordination, visual scanning, attention and mental flexibility (Grooved Pegboard, Symbol Digit Modalities Test and part B of the Trail Making Test) and showed considerably more neurobehavioural disturbances (Neurobehavioral Rating Scale-Revised) than the group without the epsilon4 allele. CONCLUSIONS: In particular, performance on neuropsychological tasks that are presumed to be related to temporal lobe, frontal lobe and white matter integrity is worse in patients with the APOE epsilon4 allele than in those without it. More neurobehavioural disturbances are observed in APOE epsilon4 carriers than in APOE epsilon2 and epsilon3 carriers.

Apolipoprotein E4↗