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R K Heaton

Publications and source records attributed to R K Heaton.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV Neurobehavioral Research Center Group.

To determine whether cerebrospinal fluid (CSF) viral burden measurements can assist in the evaluation of human immunodeficiency virus (HIV)-associated neurocognitive disorders, we quantified HIV type 1 (HIV-1) RNA in CSF. Because previous findings suggested that disease stage, lymphocytic pleocytosis, and HIV-1 RNA levels in plasma may influence CSF viral burden, these variables were examined as potential modifying factors. HIV-1 RNA levels were quantified by using a reverse transcriptase-polymerase chain reaction assay. Performance on a comprehensive neuropsychological (NP) battery was noted in 97 prospectively enrolled, HIV-infected subjects. Among subjects with acquired immunodeficiency syndrome (AIDS) (<200 CD4+ lymphocytes), NP impairment was associated with significantly higher CSF RNA levels (3.1 vs 1.8 log10 copies/ml; p = 0.02); most impaired subjects met criteria for HIV-associated dementia or minor cognitive-motor disorder. In subjects without AIDS, CSF RNA and NP impairment were unrelated. Before AIDS, CSF RNA was strongly correlated to plasma RNA and to pleocytosis, but in AIDS, CSF and plasma RNA were independent. In conclusion, we found elevated CSF HIV-1 RNA levels in NP impaired subjects with AIDS. Before AIDS, systemic viral replication, possibly through CD4+ mononuclear cell trafficking, may govern virus levels in CSF, whereas in AIDS, CD4 cell depletion may unmask a correlation between increased productive central nervous system HIV infection and clinical neurocognitive disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center.

To determine the neuropathological substrate of human immunodeficiency virus (HIV)-associated neurocognitive disorders, we examined persons with acquired immunodeficiency syndrome before their death and related their antemortem neuropsychological performance to postmortem indicators of HIV encephalitis, viral burden, and presynaptic and postsynaptic neuronal injury. Of 20 prospectively examined cases, 9 were neurocognitively normal, 5 showed neuropsychological impairment, 5 had minor cognitive/motor disorder, and 1 was demented. Degree of neurocognitive impairment was strongly related to the amount of dendritic simplification based on microtubule-associated protein 2 immunohistochemical staining, somewhat less so to a semiquantitative viral burden score based on numbers of HIV gp41-immunoreactive cells, and much less so to the presence of multinucleated giant cells or microglial nodules. It appears that even milder neurocognitive impairment reflects microneuroanatomical injury to synaptic structures.

AIDS-Related Opportunistic Infections↗
PubMed1997

The Quality of Well-Being scale in asymptomatic HIV-infected patients. HNRC Group. HIV Neural Behavioral Research Center.

We review applications of the Quality of Well-Being (QWB) scale for use in studies of human immunodeficiency virus (HIV)-infected patients. The QWB scale is a preference-weighted decision theory-based measure that summarizes outcomes in terms of quality-adjusted life years (QALYs). In order to validate the QWB scale for HIV-infected patients, the measure was administered in the University of California, San Diego (UCSD) HIV Neural Behavioral Research Center (HNRC). Data are presented for a cohort of 400 HIV-positive-infected men and 114 HIV-uninfected male controls. The evidence suggests that the QWB scale is a significant prospective predictor of mortality. The QWB scale was concurrently associated with the number of CD4+ lymphocytes and ratings of neurological impairment based upon clinical evaluations. Further, the QWB scale was related to neuropsychological assessments derived from formal tests of cognitive functioning. Neuropsychological impairments may be associated with income loss for affected patients. The QWB scale scores were lower among patients with clinical depression. We conclude that the QWB scale is an appropriate general health outcome measure for use in observational studies and clinical trials for patients with HIV disease.

Case-Control Studies↗
PubMed1997

Is it possible to be schizophrenic yet neuropsychologically normal?

This study identified and characterized a group of schizophrenic patients without neuropsychological (NP) impairment. A comprehensive NP battery was administered to 171 schizophrenic outpatients and 63 normal comparison participants. Each participant's NP status was classified through blind clinical ratings by 2 experienced neuropsychologists; 27% of the schizophrenics were classified as NP normal. The NP-normal and NP-impaired schizophrenics were similar in terms of most demographic, psychiatric, and functional characteristics, except that NP-normal patients had less negative and extrapyramidal symptoms, were on less anticholinergic medication, socialized more frequently, and were less likely to have had a recent psychiatric hospitalization. The existence of NP-normal schizophrenics suggests that the pathophysiology underlying the cognitive deficits often associated with schizophrenia may be distinct from that causing some of its core psychiatric features.

Adult↗
PubMed1997

Memory for verbal information in individuals with HIV-associated dementia complex. HNRC Group.

Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan, & Price, 1986).

AIDS Dementia Complex↗
PubMed1997

Neurocognitive impairment in human immunodeficiency virus infection is correlated with sexually transmitted disease history.

BACKGROUND AND OBJECTIVES: Neurocognitive impairment is common in human immunodeficiency virus (HIV)-infected subjects. The relationship of sexually transmitted diseases to neurocognitive changes is unknown. GOAL: To establish whether HIV-infected patients with a history of syphilis or gonorrhea have a higher rate of neurocognitive dysfunction. STUDY DESIGN: Neurocognitive function was measured by a battery of quantitative tests in a 453-person HIV-infected cohort and a 219-person HIV-seronegative control group. Neurocognitive function was then correlated with histories of either syphilis or gonorrhea to assess for possible relationships between these sexually transmitted diseases and neurologic impairment. RESULTS: Human immunodeficiency virus-infected subjects with a history of either syphilis or gonorrhea tended to perform worse on neurocognitive testing than their counterparts. This difference could not be explained by educational attainment, age, race or CD4 cell count, and was not noted in the HIV-uninfected control subjects. CONCLUSIONS: Sexually transmitted diseases in HIV-infected subjects are correlated with neurocognitive impairment through an unidentified mechanism.

Adult↗
PubMed1997

Nondementia nonpraecox dementia praecox? Late-onset schizophrenia.

Schizophrenia has traditionally been viewed as a psychotic disorder with onset in adolescence or early adulthood and a deteriorating course. Over the past decade, the authors have been studying patients meeting DSM-III-R as well as specified research criteria for late-onset schizophrenia (onset after age 45) and several comparison groups with psychiatric, neurologic, neuropsychologic, brain-imaging, psychophysiological, and psychosocial assessments. Results to date suggest a number of similarities and differences between late-onset schizophrenia and comparison groups of other older patients with psychoses (including earlier-onset schizophrenia). Later-onset schizophrenia is probably a neurobiologically distinct subtype of schizophrenia. Differential involvement of cortico-striato-pallido-thalamic circuitry may explain differences in age at onset. The authors propose a new conceptual model for level of functioning at different stages of life in late-onset schizophrenia.

Adult↗
PubMed1997

Direct assessment of functional status in older patients with schizophrenia.

OBJECTIVE: There has been a growing trend in medicine to evaluate the impact of illness on functional abilities. Such studies typically rely on the patient's or caregiver's report. The goal of this study was to assess directly the functional capacity of psychiatric patients, especially older ones. METHOD: The subjects were 55 outpatients with schizophrenia and 72 normal persons ranging in age from 45 to 86 years. The subjects were administered the Direct Assessment of Functional Status Scale, which assess behaviour during simulated daily activity tasks in the areas of time orientation, communication, transportation, finance, shopping, grooming, and eating. RESULTS: The patients with schizophrenia had significantly greater disability than the normal subjects according to total scale scores as well as the communication, transportation, finance, and shopping subscale scores. Global cognitive status was the best predictor of total scale score. CONCLUSIONS: The Direct Assessment of Functional Status Scale is a promising instrument for functional assessment in outpatients with schizophrenia.

Activities of Daily Living↗
PubMed1997

Neuropsychological performance of HIV-1 infected men with major depression. HNRC Group. HIV Neurobehavioral Research Center.

This study sought to determine if human immunodeficiency virus-type 1 (HIV-1) infected depressed men were more likely to be neuropsychologically impaired than their nondepressed counterparts. Subjects were 47 HIV-1 infected men who met DSM-III-R criteria for current major depressive disorder (MDD) and 47 HIV-1 infected nondepressed male controls (M age = 34.2 years) equated on HIV-1 disease severity, demographics, and drug use. The psychiatric interview included the Structured Clinical Inventory for the DSM-III-R, and Hamilton Rating Scale for Depression. The neuropsychological battery included tests covering 8 functional domains based on an expanded Halstead-Reitan Battery. The medical assessment included a history and physical examination, immunologic staging, and evaluation of prescription and recreational drug use. Prevalence of global neuropsychological impairment in the two groups (depressed vs. control) did not differ [53% vs. 38% respectively; chi 2(1, N = 94) = 2.11, p > .05]. While syndromically depressed patients performed less well than nondepressed individuals on memory tests [delayed retention portions of the Story Memory Test: F(1,91) = 5.34, p < .05; and Figure Memory Test: F(1,90) = 4.16, p < .05], the majority of depressed participants (64%) did not have clinically impaired memory. No relationship between neuropsychological impairment and severity of depression was observed. The results suggest that, while HIV-1 infected men with major depression may perform more poorly than nondepressed men on some aspects of memory tasks, they are not more likely to evidence clinically significant neurocognitive impairment.

Adult↗
PubMed1996

Impairment of the semantic network in schizophrenia.

It is well established that patients with schizophrenia display a variety of language impairments. Despite considerable research, however, the underlying mechanisms of the language deficits in schizophrenia remain unclear. Representations of semantic networks of 56 patients with schizophrenia and 28 normal comparison (NC) subjects of similar ages and educational levels were generated by multidimensional scaling and Pathfinder analyses of their responses on the Animal Fluency Test. On the basis of traditional scoring techniques (i.e., total number of correct animal names generated in 60 s), all patients performed significantly worse than the NC subjects. More detailed analyses of the underlying semantic networks revealed that performance in the patients varied according to age of onset and subtype of schizophrenia. The semantic network of patients with late-onset schizophrenia (i.e., with onset after age 45) was virtually identical to that of the NC group. In contrast, the semantic network of patients with a younger age of onset was disorganized and differed significantly from that of the NC subjects. Findings demonstrated that patients with nonparanoid subtypes displayed greater disorganization in their semantic networks than patients with a paranoid subtype. Although general fluency impairments (e.g., difficulties in initiation, retrieval, and search mechanisms) may be sensitive to schizophrenia, per se, specific deficits in the structure of semantic knowledge may be associated with certain characteristics of individual patients with schizophrenia, such as an earlier age of onset and nonparanoid subtype.

Adult↗
PubMed1996

Discriminability of the Wisconsin Card Sorting Test using the standardization sample.

The four neurological patient groups and the normals from the Wisconsin Card Sorting Test (WCST) standardization sample were used to examine the discriminability of the WCST's indices. Results reveal consistent differentiation of normals from the patient groups on all WCST variables, with classification rates averaging 71% accuracy. However, patient groups with frontal, diffuse, and nonfrontal lesions were not consistently discriminable from each other. The results suggest that the WCST is most usefully conceptualized as a measure of executive abilities that involves the frontal lobes, but should not be considered solely as a marker of isolated frontal lobe pathology.

Adult↗
PubMed1996

Clinical and neuropsychological comparison of psychotic depression with nonpsychotic depression and schizophrenia.

OBJECTIVE: This study compared the clinical and neuropsychological characteristics of patients with psychotic depression to those of patients with nonpsychotic depression and patients with schizophrenia. METHOD: Two hundred eighteen patients over the age of 45, including 30 who met the DSM-III-R criteria for unipolar major depression with psychotic features, 28 with nonpsychotic unipolar major depression, and 160 with schizophrenia, were examined. Subjects were evaluated on several clinical measures as well as on neuropsychological tests of attention, learning, memory (retention), psychomotor speed, and motor skills. RESULTS: The three groups were comparable in age and education. The severity of depressive symptoms in the depressed patients with and without psychosis was similar. The patients with psychotic depression were comparable to those with schizophrenia on the neuropsychological measures; they were more impaired than the patients with nonpsychotic depression on the measures of psychomotor speed, motor skills, attention, and learning. The cognitive deficits seemed to be trait-related. CONCLUSIONS: The findings provide additional support for the validity of psychotic depression as a diagnostic category distinct from nonpsychotic depression.

Age of Onset↗
PubMed1996

A clinical and neuropsychological comparison of delusional disorder and schizophrenia.

The authors evaluated 14 middle-aged and elderly patients with delusional disorder (DD) and 253 patients with schizophrenia (SC); all patients met DSM-III-R criteria. Because the DD patients were older and had a later age at onset of illness, a sub-sample of 50 SC patients with illness onset after age 40 was compared with the 14 DD patients on clinical and neuropsychological characteristics. The DD group had a less frequent history of past hospitalization but more severe overall psychopathologic symptoms. Level of neuropsychological impairment seemed somewhat lower in the DD group, but differences were nonsignificant because of small sample size. Diagnoses remained stable during up to 8 years' follow-up (average 4 years). These preliminary findings provide partial support to the clinical categorization of DD as a disorder distinct from SC.

Age of Onset↗
PubMed1996

Neurological Symptoms, Not Signs, Are Common in Early HIV Infection.

UNLABELLED: Objective. To examine the cross-sectional prevalence of neurological symptoms and signs in a large cohort of human immunodeficiency virus (HIV)-seropositive men, and determine the relationship of the symptoms to disease stage, immunologic markers, and independent variables from neuropsychological (NP) testing and psychiatric interview. METHODS: One hundred-nine controls and 386 HIV-infected volunteers enrolled in the HIV Neurobehavioral Research Center (HNRC) longitudinal study. The majority, without acquired immune deficiency syndrome (AIDS), were screened for alcohol/substance abuse; previous diagnosis of HIV-associated dementia; and HIV-unrelated developmental, neurological, medical, and neurobehavioral conditions which potentially impair cognition; and underwent a structured neurological interview and examination, standardized NP testing, and psychiatric interview as part of a more extensive battery. A large subset (N = 377) underwent lumbar puncture for cerebrospinal fluid (CFS) examination. We examined the relationship of sixteen select but independent variables, using stepwise multiple regressions, from demographic/staging, immunological, NP, and psychiatric domains to neurological symptoms in an effort to identify possible predictors of subclinical nervous systems involvement. Results. All categories of neurological symptoms were significantly more prevalent among medically asymptomatic (CDC stage A) subjects than controls, with a further rise in prevalence in those with more advanced stages of infection. The most marked rise was seen in cognitive and sensorimotor complaints. In contrast, significant findings on neurological examination were evident in only the sicker (stage C) subjects. Stage of illness, serum &beta;2-microglobulin, psychiatric indices of depressed mood or anxiety, and NP "motor" performance were the most significant independent variables associated with the presence of neurological symptoms. CSF pleocytosis was seen early (CDC stage A), and may reflect the presence of HIV in the central nervous system (CNS) at the least stages of infection. We also confirmed the value of CSF &beta;2m and neopterin as important markers of advancing disease stage. Whether they predict subclinical CNS involvement is to be determined by longitudinal observations. Conclusion. Neurological complains are common in medically asymptomatic HIV subjects whereas signs are not. The symptoms correlate with commonly determined independent measures of depression, anxiety, NP tests of fine motor speed and strength, as well as indices of disease worsening (CDC stage, serum &beta;2m).

AIDS Dementia Complex↗
PubMed1995

Risk of tardive dyskinesia in older patients. A prospective longitudinal study of 266 outpatients.

BACKGROUND: Neuroleptic-induced tardive dyskinesia (TD) is a major iatrogenic disorder that is more prevalent among older patients. The objective of this study was to determine the incidence of and risk factors for TD in neuroleptic-treated patients over age 45 years. METHODS: We studied 266 middle-aged and elderly outpatients with a median duration of 21 days of total lifetime neuroleptic exposure at study entry. Most patients were treated throughout the study with either a high-potency or a low-potency neuroleptic and maintained on relatively low doses. The patients were followed up at 1- to 3-month intervals with "blind" assessment of psychopathologic condition, clinically as well as instrumentally (ie, using electromechanical sensors with computerized data reduction, including spectral analysis) evaluated movement disorder, and global cognitive function. RESULTS: Cumulative incidence of TD was 26%, 52%, and 60% after 1, 2, and 3 years, respectively. The principal risk factors for TD were duration of prior neuroleptic use at baseline, cumulative amount of high-potency neuroleptics, history of alcohol abuse/dependence, borderline or minimal dyskinesia, and tremor on instrumental assessment. CONCLUSION: Use of higher amounts of neuroleptics, particularly high-potency ones, should be avoided in older patients, patients with alcohol abuse/dependence, or patients with a subtle movement disorder at baseline; these patients are at a higher risk of developing TD.

Age Factors↗
PubMed1995

The nature of learning and memory impairments in schizophrenia.

The California Verbal Learning Test was used to characterize the learning and memory impairment in schizophrenia (SC) and to evaluate potential clinical and demographic factors associated with this impairment. SC patients (n = 175) performed worse than normal comparison (NC) subjects (n = 229) on all learning, recall, and recognition memory measures. The most important clinical correlates of these impairments were earlier age of onset, more negative symptoms, and greater anticholinergic medication dosage. SC patients showed a prominent retrieval deficit as indicated by disproportionate improvement when tested in a recognition, rather than a free recall, format. A residual impairment seen with recognition testing suggests a mild encoding deficit as well. In contrast, the relative absence of a storage deficit is suggested by the lack of rapid forgetting. Using a discriminant function analysis that differentiates cortical dementia [i.e., Alzheimer's disease (AD)], subcortical dementia [i.e., Huntington's disease (HD)], and normals, it was found that 50% of the SC patients were classified as having a subcortical memory profile and 35% were classified as having a normal profile, whereas only 15% were classified as having a cortical memory profile. Although these findings reflect the clinical heterogeneity often found in SC, results suggest that most SC patients demonstrate a pattern of learning and memory impairments that resembles the pattern seen in patients with primary subcortical (specifically striatal) pathology.

Adult↗
PubMed1995

The HNRC 500--neuropsychology of HIV infection at different disease stages. HIV Neurobehavioral Research Center.

The present study examined neuropsychological (NP) functioning and associated medical, neurological, brain magnetic resonance imaging (MRI), and psychiatric findings in 389 nondemented males infected with Human Immunodeficiency Virus-Type 1 (HIV-1), and in 111 uninfected controls. Using a comprehensive NP test battery, we found increased rates of impairment at each successive stage of HIV infection. HIV-related NP impairment was generally mild, especially in the medically asymptomatic stage of infection, and most often affected attention, speed of information processing, and learning efficiency; this pattern is consistent with earliest involvement of subcortical or frontostriatal brain systems. NP impairment could not be explained on the bases of mood disturbance, recreational drug or alcohol use, or constitutional symptoms; by contrast, impairment in HIV-infected subjects was related to central brain atrophy on MRI, as well as to evidence of cellular immune activation and neurological abnormalities linked to the central nervous system.

AIDS Dementia Complex↗