Biomedical subjects

R K Heaton

Publications and source records attributed to R K Heaton.

At least 37 records · Page 2Linked to original sources

PubMed1999

Further crossvalidation of regression-based neuropsychological norms with an update for the Boston Naming Test.

Regression-based norms for the Trail Making Test, Boston Naming Test, and Wisconsin Card Sorting Test, which we published in 1991 and 1993, have been criticized by Fastenau (1998) as having overcorrected for demographic influences in a sample of 63 older adults. We present data from new, independent participant samples that are consistent with expectations from the regression-based norms. We propose that Fastenau's findings in this instance resulted from the nonrepresentative nature of his relatively small sample, rather than from statistical deficiencies of regression based norms. Our currently published norms on one of the four tests considered here, the Boston Naming Test, are based upon a participant sample that was small and had inadequate representation of young adults. We address this by providing updated norms based on a much larger and more representative sample (N = 531).

Adult↗

PubMed1999

Cortical synaptic density is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. HNRC Group. HIV Neurobehavioral Research Center.

Dendritic and synaptic damage (without frank neuronal loss) may be seen in milder human immunodeficiency virus (HIV)-related cognitive disorders. Synapse volume estimates, performed by stereological methods, could enhance the ability to detect subtle neuronal changes that may accompany cognitive impairment in HIV infection. For the present study, synaptic density and neuronal number were assessed by combined stereology/confocal microscopy and these measures were then correlated with ante-mortem levels of cognitive performance in AIDS patients. Three-dimensional stereological measures showed a significant correlation between reduced synaptic density and poor neuropsychological performance. To evaluate the specificity of any observed associations, additional variables including viral burden, astrogliosis and number of calbindin-immunoreactive neurons were measured. Factor analysis of a set of neuropathological variables revealed two factors; one defined by synaptic density and volume fraction, calbindin pyramidal neuronal densities and viral burden; the second by astrocytosis and calbindin interneuron density. Only the first factor correlated significantly with neuropsychological functioning during life. It is concluded that a combination of factors including synaptic damage, specific neuronal loss and increasing viral load underlies HIV-associated cognitive impairment. As synaptic damage is potentially reversible, early diagnosis and treatment of mild cogntive disorders may improve functioning and prevent the progression of brain disease.

AIDS Dementia Complex↗

PubMed1999

Cognitive deficits and psychopathology in institutionalized versus community-dwelling elderly schizophrenia patients.

We evaluated psychiatric symptoms and neurocognitive functioning among 25 institutionalized and 25 outpatient DSM-IV-diagnosed schizophrenia patients, as well as 25 middle-aged and elderly normal comparison subjects. All subjects were assessed with the Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, modified Simpson-Angus Extrapyramidal Symptom Scale, the Abnormal Involuntary Movement Scale, and the Mattis Dementia Rating Scale (DRS). The two patient groups had similar levels of depressive symptoms, but the institutionalized patients had more severe positive and negative symptoms and were on higher doses of neuroleptic medication. The institutionalized patients had significantly more cognitive impairment on the DRS than outpatients and normal comparison subjects, particularly on the subscales of initiation/perseveration, conceptualization, and memory. Results are discussed in terms of the possible neuropathology associated with cognitive impairment in chronic schizophrenia.

Aged↗

PubMed1999

Norms for letter and category fluency: demographic corrections for age, education, and ethnicity.

Letter and category fluency tasks are used to assess semantic knowledge, retrieval ability, and executive functioning. They appear to be useful in detecting different types of dementia, but accurate detection of neuropsychological impairment relies on appropriate normative data. Multiple regression analysis was used to develop demographically corrected norms for letter and category fluency in 768 normal adults. T-score equations were developed on a base subsample of 403, and crossvalidated on a separate subsample (n = 365). Participants ranged in age from 20 years to 101 years; in educational level from 0 to 20 years; 55% were Caucasian and 45% were African American. Together, age, education, and ethnicity were significant predictors of letter and category fluency performance, accounting for 15% and 25% of variance, respectively. Formulas and tables for converting raw fluency scores to demographically corrected T scores are presented.

Adult↗

PubMed1999

Test-retest reliability and practice effects of expanded Halstead-Reitan Neuropsychological Test Battery.

Test-retest reliabilities and practice effects of a broad range of neuropsychological measures were examined in 384 normal or neurologically stable adults. Median test-retest interval was 11 months (range 3-16 months). The reliability estimates for most of the measures are reasonably good, ranging from .70 to low .90s. An exception is the relatively poor reliabilities of most memory measures. For all test measures, the value on initial testing is a strong determinant of the value on the second examination. Practice effects are seen on most measures. The magnitude of the practice effects, however, varies as a function of type of measure, test-retest interval, age, and overall competency level of the participant. This study provides several types of retest information that may be useful for future research and clinical work: comparative reliabilities of the various measures, estimate of error variability associated with each administration, standard deviation of the change, and comparative magnitude of practice effects on various tests.

Adult↗

PubMed1999

Schizoaffective disorder: a form of schizophrenia or affective disorder?

BACKGROUND: The diagnostic status of schizoaffective disorder continues to be controversial. Researchers have proposed that schizoaffective disorder represents a variant of schizophrenia or affective disorder, a combination of the 2, or an intermediate condition along a continuum between schizophrenia and affective disorder. METHOD: We compared outpatients aged 45 to 77 years with DSM-III-R diagnosis of schizoaffective disorder (N = 29), schizophrenia (N = 154), or nonpsychotic mood disorder (N = 27) on standardized rating scales of psychopathology and a comprehensive neuropsychological test battery. A discriminant function analysis was used to classify the schizoaffective patients based on their neuropsychological profiles as being similar either to schizophrenia patients or to those with nonpsychotic mood disorder. RESULTS: The schizoaffective and schizophrenia patients had more severe dyskinesia, had a weaker family history of mood disorder, had been hospitalized for psychiatric reasons more frequently, were more likely to be prescribed neuroleptic and anticholinergic medication, and had somewhat less severe depressive symptoms than the mood disorder patients. The schizophrenia patients had more severe positive symptoms than the schizoaffective and mood disorder patients. The neuropsychological performances of the 2 psychosis groups were more impaired than those of the nonpsychotic mood disorder patients. Finally, on the basis of a discriminant function analysis, the schizoaffective patients were more likely to be classified as having schizophrenia than a mood disorder. CONCLUSION: These findings suggest that schizoaffective disorder may represent a variant of schizophrenia in clinical symptom profiles and cognitive impairment.

Aged↗

PubMed1999

Neuropsychological impairment-associated visual field deficits in HIV infection. HNRC Group. HIV Neurobehavioral Research Center.

PURPOSE: To examine the relationship between loss in peripheral visual sensitivity and neuropsychological functioning in seropositive patients with human immunodeficiency virus (HIV) without infectious retinopathy. METHODS: Subjects carefully screened for retinal disease and well-matched across demographic and medical variables were grouped according to normal (perimetry-nl) versus abnormal (perimetry-abnl) performance on achromatic automated perimetry and short-wavelength automated perimetry, standard clinical ophthalmologic measures of visual function. All subjects completed a detailed neuropsychological test battery and were classified as impaired or unimpaired, globally and across eight neurocognitive domains. Subjects were also classified according to whether they met diagnostic criteria for minor cognitive/motor disorder (MCMD) or HIV-associated dementia (HAD). RESULTS: Visual field loss was associated with lower performance in the abstraction, perceptual-motor, learning, and motor domains. Significant group differences were also found on numerous individual neuropsychological tests. Based on clinical ratings, we found deficits in learning and motor functioning. No perimetry-nl subjects met criteria for MCMD or HAD, whereas 32% of perimetry-abnl subjects met diagnostic criteria for syndromic cognitive disorders (five MCMD and one HAD). In a subset of subjects who underwent a lumbar puncture, there was a trend for the perimetry-abnl group to have a higher concentration of beta2 microglobulin, a marker for central nervous system immune activation. CONCLUSIONS: These results suggest that in some HIV-infected people reduced visual function may be caused by nonretinal disease, and perimetry may present a sensitive measure of HIV-related brain dysfunction.

Adult↗

PubMed1998

Cerebrospinal fluid tau protein is not elevated in HIV-associated neurologic disease in humans. HIV Neurobehavioral Research Center Group (HNRC).

We measured the concentrations of the neuron-specific protein, tau, in the cerebrospinal fluid (CSF) of 32 neurologically characterized HIV-infected (HIVpos) subjects and nine matched seronegative (HIVneg) controls using a sensitive ELISA assay. Of 32 HIVpos subjects, nine had HIV-associated neurocognitive disorders, and nine had clinically diagnosed peripheral neuropathies. CSF tau levels in subjects with HIV-associated neurocognitive disorders were similar to those in HIVneg subjects (185 +/- 83 vs. 223 +/- 106 pg/ml; P = 57). CSF tau levels in HIVpos subjects with peripheral neuropathies did not differ from those without neuropathies (320 +/- 190 vs. 251 +/- 185; P = 23). In summary, CSF tau levels were not elevated in patients with HIV-associated neurologic disease.

AIDS Dementia Complex↗

PubMed1998

Correlates of functional status in older patients with schizophrenia.

There is a growing recognition of the importance of quantifying the impact of illness on functional abilities. Measures of function frequently rely on a self-report. Few studies have directly assessed functional capacity in psychiatric patients, especially older ones who may be at an increased risk for disability. Subjects were 102 middle-aged and elderly outpatients with DSM-III-R or DSM-IV diagnosis of schizophrenia or schizoaffective disorder, and 66 normal comparison subjects, ranging in age from 45 to 86. The Direct Assessment of Functional Status (DAFS), a standardized measure of behavior during simulated daily activity tasks (i.e. time orientation, communication, transportation, finance, shopping, grooming and eating) was used to quantify levels of disability. Schizophrenic patients demonstrated significantly greater disability than normal subjects. An evaluation of specific behaviors indicated that the patients were significantly more limited than comparison subjects across all subscales of the DAFS except for grooming and eating. A lower level of formal education, greater severity of extrapyramidal symptoms, and greater cognitive deficits, but not severity of symptoms of schizophrenia, were related to lower DAFS scores. Relative to published findings, schizophrenic patients appeared more disabled than outpatients with major depression, but less disabled than those with Alzheimer's disease. The DAFS is a useful instrument for characterizing functional abilities in older patients with schizophrenia. Our findings of significant functional disability in older schizophrenic patients have implications for treatment as well as allocation of health-care resources.

Activities of Daily Living↗

PubMed1998

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

AIDS Dementia Complex↗

PubMed1998

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia.

Age of onset of schizophrenia (AOS) may be largely determined by neurobiological factors. We examined in a diverse sample of schizophrenia out-patients the relationships of AOS with neuropsychological abilities and structural brain abnormalities as measured on cerebral magnetic resonance imaging (MRI). A total of 82 out-patients meeting DSM-III-R criteria for schizophrenia were evaluated with a comprehensive neuropsychological battery and semi-automated quantitatively analysed cerebral MRI. Earlier AOS correlated with poorer performance in learning and abstraction/cognitive flexibility, and with larger volumes of caudate and lenticular nuclei, and smaller volume of thalamus on MRI. A model for predicting AOS consisting of abstraction and thalamic and caudate volumes remained significant after controlling for duration of illness, current age and daily neuroleptic dose. In conclusion, AOS may be related to specific rather than general measures of cognitive performance and structural brain abnormalities.

Adult↗

PubMed1998

The Paced Auditory Serial Addition Task (PASAT): norms for age, education, and ethnicity.

The Paced Auditory Serial Addition Task (PASAT) is often used to measure attention, concentration, working memory, and speed of information processing. Using a modified 200-item version of the PASAT with presentation rates of 3.0, 2.4, 2.0, and 1.6 items per second, we analyzed demographic influences on test performance in a large sample (N = 566) of healthy North American adults. We found that age, education, and ethnicity were significant predictors, accounting for nearly 23% of the variance in test performance. We discuss these results in comparison to previous normative studies, and present a formula and tables for computing age, education, and ethnicity-adjusted T scores for performance on the PASAT 200.

Adult↗

PubMed1998

Neuropsychologic impairment in patients with nonepileptic seizures.

Patients with nonepileptic seizures (NES), those with epileptic seizures (ES), and normal controls were compared on a battery of neuropsychologic tests. Diagnoses were made after intensive electroencephalogram (EEG) monitoring. Excluded from the study were patients with both ES and NES, as well as patients with ES who had evidence of structural brain damage. On all neuropsychologic measures, the two seizure groups were significantly impaired relative to the controls, but there were no significant differences between the ES and NES group performances. Additional neuropsychologic measures were obtained on the two seizure groups but not controls, and again there were no significant differences between the two seizure groups. Further analyses suggested that the NES group's impairment was related to emotional factors. The Minnesota Multiphasic Personality Inventory (MMPI)/MMPI-2 and the Portland Digit Recognition Test were helpful in classifying patients by seizure group. Our results, which are consistent with those of previous studies, suggest that neuropsychologic abnormalities are not pathognomonic of brain dysfunction in this population. However, the Portland Digit Recognition Test (PDRT) and measures of personality are useful for classification purposes in the differential diagnosis of epileptic and nonepileptic seizures.

Journal Article↗

PubMed1998

The effect of African-American acculturation on neuropsychological test performance in normal and HIV-positive individuals. The HIV Neurobehavioral Research Center (HNRC) Group.

Two studies were conducted to examine the relationship of acculturation to neuropsychological test performance among (1) medically healthy, neurologically normal African Americans (N = 170); and (2) HIV positive (HIV+) subgroups of African Americans and Whites (Ns = 20) matched on age, education, sex, and HIV disease stage. Acculturation was measured through self report for all participants, and linguistic behavior (Black English use) was assessed in a subset of medically healthy individuals (N = 25). After controlling for the effects of age, education, and sex, medically healthy African Americans who reported less acculturation obtained lower scores on the WAIS-R Information subtest and the Boston Naming Test than did more acculturated individuals. Black English use was associated with poor performance on Trails B and the WAIS-R Information subtest. HIV+ African Americans scored significantly lower than their HIV+ White counterparts on the Category Test, Trails B, WAIS-R Block Design and Vocabulary subtests, and the learning components of the Story and Figure Memory Tests. However, after accounting for acculturation, ethnic group differences on all measures but Story Learning became nonsignificant. These results suggest that there are cultural differences within ethnic groups that relate to neuropsychological test performance, and that accounting for acculturation may improve the diagnostic accuracy of certain neuropsychological tests.

Acculturation↗

PubMed1998

Neuropsychological comparisons of Spanish-speaking participants from the U.S.-Mexico border region versus Spain.

Two samples of participants from the U.S.-Mexico Borderland (N = 185) versus Spain (N = 205) were compared on 16 Spanish-language neuropsychological measures. In most measures the two samples obtained similar results. There were some significant main effects of place of birth and some significant interactions between education and place of birth. Differences between the samples diminished with increasing levels of education. Within the Borderland sample, percent of life span spent in the U.S. and bilingual status were correlated with performance in some tests. Increased percent of life span spent in the U.S. was negatively correlated with performance on a Spanish word-generation task, and positively correlated with performance on the Wisconsin Card Sorting Test. Bilingual Borderland participants performed significantly better than monolingual speakers in learning a list of words. We suggest that the most likely causes for the observed interaction effects are documented regional differences in early SES-related nutrition, medical care, quality of educational experiences, and general socioeconomic conditions.

Acculturation↗

PubMed1997

Neuroleptic dose reduction in older psychotic patients.

We conducted a non-randomized, rater-blind study to safely determine the lowest effective neuroleptic dosage in older psychotic patients and to evaluate the clinical, neuropsychological, and psychosocial effects of neuroleptic dosage reduction. Twenty-seven carefully selected patients with schizophrenia and related psychotic disorders over the age of 45 had their dosage tapered by 25% each month to determine their lowest effective dosage. These patients were compared with patients similar in age, gender, and education who were currently off neuroleptics (n = 19) or maintained on neuroleptics (n = 22). All groups were followed for 11 months. Over the follow-up period, 29% of patients in the taper group, 8% of neuroleptic-free patients, and 0% of patients in the maintenance group experienced some increase in psychopathology, although there was no significant change in mean PANSS score in any group, and no patient required hospitalization. Patients in the taper group were maintained on approximately 60% of their original neuroleptic dosage after restabilization. Extrapyramidal symptoms continued to improve over time in the taper group. Neuropsychological testing did not change significantly over time except for those in the taper group who experienced a decrease in memory-retention on the Hopkins Verbal Learning Test and a significant improvement in digit vigilance and Stroop Interference Index. Carefully selected middle-aged and elderly psychotic patients can have their neuroleptic medications reduced without a significant change in psychopathology. Extrapyramidal symptoms may continue to improve gradually over time. The impact on cognition functioning needs further investigation.

Age Factors↗

PubMed1997

Evaluating the neurocognitive complications of SLE. Lessons from HIV disease.

In this paper, we have attempted to define some of the theoretical, methodological, and practical issues involved in the use of NP testing to detect, classify, and monitor neurocognitive impairment secondary to systemic lupus erythematosus. We have drawn on experience with other clinical entities-primarily HIV disease-to inform this discussion. We have argued that for the purposes of studying NP-SLE, NP testing remains the gold standard and is also the most practicable approach in most settings, be they clinical or research. At the same time, the selection of NP tests must be carefully considered, particularly in a disease such as SLE in which the neurocognitive complications arise from several etiological mechanisms, affect people at various points in the course of disease, and in which the anatomic distribution of pathology in the brain varies from patient to patient. In this context, it is safest to select a test procedure that assesses all major areas of cognitive functioning with tests for which adequate demographically adjusted norms exist. In this way, a more reliable diagnosis of neurocognitive impairment, mild neurocognitive disorder, or dementia may be made. A reliable and valid neurocognitive diagnosis is the first step in monitoring patients clinically, in designing research aimed at neuropathogenesis, or in the design of treatment trials geared toward neuroprotection or neuroremediation.

Cognition Disorders↗

PubMed1997

Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group.

OBJECTIVE: To determine if mortality is increased in individuals with human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders less severe than frank dementia. DESIGN: A prospective cohort study; median duration of follow-up was 2.4 years. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival times according to neurocognitive classification. SETTING: University-based research unit. PARTICIPANTS: A volunteer sample of 414 individuals seropositive for HIV-1. Subjects were classified at their baseline evaluation as neuropsychologically (NP) normal or abnormal (impaired in > or = 2 NP test domains). A subgroup of NP abnormal subjects met operational criteria for HIV-associated minor cognitive motor disorder; the remaining subjects were designated NP impaired. Subjects with frank dementia were excluded. MAIN OUTCOME MEASURE: Mortality. RESULTS: At the baseline evaluation, 256 (62%) of 414 subjects were designated normal; 109 (26%). NP impaired; and 49 (12%), minor cognitive motor disorder. One hundred six participants (26%) died during follow-up. Compared with the NP normal group, the unadjusted relative risk (RR) of death for all NP abnormal subjects (minor cognitive motor disorder and NP impaired) was significantly increased (RR, 1.7; 95% confidence interval [CI], 1.2-2.6; P < .005). After adjusting for concurrently measured predictors of survival (CD4 lymphocyte counts, Centers for Disease Control and Prevention HIV disease classification, hemoglobin concentration, and serum beta 2-microglobulin) in proportional hazards models, mortality for all NP abnormal subjects remained elevated (RR, 1.8; 95% CI, 1.2-2.8; P < .01). The elevation in mortality risk for subjects with minor cognitive motor disorder was statistically significant (RR, 2.2; 95% CI, 1.2-3.8; P < .01); for NP impaired subjects it was marginally significant (RR, 1.6; 95% CI, 1.0-2.8; P = .06). CONCLUSIONS: The HIV-infected individuals with NP impairment had a higher risk of dying than those without impairment. This was particularly true for those meeting syndromic diagnostic criteria.

Adult↗