Biomedical subjects

J T Becker

Publications and source records attributed to J T Becker.

At least 37 records · Page 2Linked to original sources

PubMed1999

Combination antiretroviral therapy improves psychomotor speed performance in HIV-seropositive homosexual men. Multicenter AIDS Cohort Study (MACS).

BACKGROUND: Combination antiretroviral therapy including protease inhibitors (combo+PI) is effective in suppressing systemic viral load in HIV infection, but its impact on HIV-associated cognitive impairment is unclear. OBJECTIVE: To determine whether psychomotor speed, a sensitive measure of impairment in HIV dementia, improves with combo+PI compared with other antiretroviral treatments. METHODS: A total of 411 HIV-seropositive (HIV+) homosexual men (with longitudinal neuropsychological testing) in the Multicenter AIDS Cohort Study and, in a separate analysis, 282 HIV+ homosexual men with psychomotor slowing at baseline were classified by treatment into four groups: antiretroviral naive (no antiretroviral medication treatment), monotherapy, combination antiretroviral therapy without protease inhibitors (combo-noPI), and combo+PI. We compared longitudinal performance on three tests of psychomotor speed: the Grooved Pegboard (GP) (nondominant and dominant hands), Trail Making Test B, and the Symbol Digit Modalities Test (SDMT). RESULTS: Relative to antiretroviral-naïve and monotherapy participants, on the GP nondominant hand test, combo+PI participants with abnormal baseline neuropsychological testing showed improved performance (difference = +0.63 standard deviation [SD], p = 0.02). For the SDMT, both combo+PI participants (difference = +0.26 SD, p = 0.03) and combo-noPI participants (difference = +0.29 SD, p = 0.01) with abnormal baseline neuropsychological testing improved compared with antiretroviral-naïve and monotherapy groups. CONCLUSION: Combo+PI and combo-noPI are associated with improved psychomotor speed performance in HIV+ homosexual men with abnormal neuropsychological testing.

Adult↗

PubMed1999

Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease.

OBJECTIVE: To examine whether the use of psychiatric medication and the presence of abnormal behaviors affects the progression of Alzheimer disease. DESIGN: Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: (1) Mini-Mental State Examination score of 9 or lower; (2) Blessed Dementia Rating Scale score of 15 or higher for activities of daily living; (3) nursing home admission; and (4) death, evaluated using a proportional hazard model with 9 variables: psychosis, insomnia, wandering, aggression, psychomotor agitation, depression, and use of antidepressants, antipsychotic agents, or sedatives/hypnotics. SETTING: Multidisciplinary dementia research clinic. PATIENTS: We examined baseline and follow-up behavioral symptoms and the use of psychiatric medication in 179 mildly to moderately impaired patients with probable Alzheimer disease participating in a longitudinal study of dementia. Patients were observed from 2.4 to 172 months (mean duration +/- SD, 49.5+/-27.4 months). RESULTS: Nine patients (5%) were taking sedatives/ hypnotics; 16 (9%), antipsychotic agents; and 22 (12%), antidepressants at study entry. Patients taking antipsychotic agents had lower Mini-Mental State Examination scores and higher Blessed Dementia Rating Scale scores for activities of daily living than patients not taking any medication. Using proportional hazard analysis with time-dependent covariates for individual psychiatric symptoms and medications, we found that the development of psychosis was associated with functional decline (time to Blessed Dementia Rating Scale score of > or =15), institutionalization, aggression, and agitation with functional decline after adjusting for age at study entry, education, Mini-Mental State Examination scores, and Blessed Dementia Rating Scale scores. Use of antipsychotic medication was associated with functional decline, and sedatives/hypnotics with death. Neither the presence of psychiatric symptoms nor use of medication was associated with rate of cognitive decline (time to Mini-Mental State Examination score of < or =9). CONCLUSIONS: These findings indicate that the use of antipsychotic agents and sedatives can affect the natural course of Alzheimer disease. Psychosis, agitation, and aggression are important predictors of outcome, even when the effects of medication to treat them is taken into account.

Aged↗

PubMed1999

Working memory(s).

Working memory is variously defined as a set of linked and interacting information processing components that maintain information in a short-term store (or retrieve information into that store) for the purpose of the active manipulation of the stored items. The purpose of the this Special Issue is to present data relevant to the question of the functional organization of working memory. In this Introduction we review the two models of working memory and suggest that some of the similarities may be more apparent than real. We further suggest that the two models describe different systems that are specialized for different kinds of stimuli and for different kinds of information processing.

Humans↗

PubMed1999

A comment on the functional localization of the phonological storage subsystem of working memory.

Working memory, as defined by Baddeley and Hitch, is an interactive set of cognitive processes responsible for holding information online and available for analysis. Part of that system is a specialized subsystem devoted to maintaining verbal information; the verbal "slave" subsystem has as a core component a phonological store. For many years, the anatomical locus of the phonological store has been thought to be in the supramarginal and angular gyri of the speech dominant hemisphere, and functional neuroimaging studies provide broad support for this localization. However, a finer grained analysis of published experiments reveals two possible foci for the phonological store within the parietal lobe, neither of which has a pattern of functional activation that is fully consistent with the Baddeley and Hitch model. The purpose of the present paper is to review several studies relevant to the question of the localization of the phonological store and to suggest possible reasons the results are discrepant.

Humans↗

PubMed1999

Functional neuroanatomy of semantic memory: recognition of semantic associations.

In an effort to examine the functional neuroanatomy of semantic memory, we studied the relative cerebral blood flow of eight healthy young subjects using 15O-water positron emission tomography (PET). Relative to a visual baseline control condition, each of four visual matching-to-sample tasks activated components of the ventral visual processing stream, including the inferior occipital and temporal cortices. Contrasting the task with the highest semantic component, a variation on the Pyramids and Palm Trees paradigm, with a size discrimination task resulted in focal activation in the anterior inferior temporal lobe, focused in the parahippocampal gyrus. There was additional activation in BA47 of the inferior frontal cortex. These data replicate and extend previously reported results using similar paradigms, and are consistent with cognitive neuropsychological models that stress the executive role of BA47 in semantic processing tasks.

Adolescent↗

PubMed1999

Combined effects of HIV-infection status and psychosocial vulnerability on mental health in homosexual men.

The present study examines psychiatric symptomatology and syndromal depression among 174 HIV+ and 760 HIV- homosexual men enrolled in the Pittsburgh site of the Multicenter AIDS Cohort Study (MACS). A central study goal was to determine whether men's psychosocial status in the areas of demographics, social supports, and coping, in combination with their HIV-infection status, was associated with mental health. Cross-sectional analyses indicated that HIV+ men had significantly higher levels of psychiatric symptomatology and syndromal depression than HIV- men. However, multivariate analyses showed that these associations only appeared among HIV+ men with certain psychosocial characteristics. HIV+ men who were younger, lacked full-time employment, claimed relatively high support from their relatives, and demonstrated high use of active behavioral coping strategies were at greater risk for psychiatric symptomatology and/or syndromal depression. Further, sense of mastery and frequent use of avoidant coping strategies were highly predictive of psychiatric outcomes irrespective of HIV status. The findings suggest that knowledge of an individual's HIV status per se will be inadequate for valid assessment of psychological risks. Rather, any association of HIV status and mental health will depend largely on other psychosocial characteristics that foster vulnerability or resistance to distress in these men.

Adaptation, Psychological↗

PubMed1999

Neuropsychological test performance in the acquired immunodeficiency syndrome: independent effects of diagnostic group on functioning.

Individuals infected with the acquired immunodeficiency syndrome (AIDS) are at risk for developing cognitive impairment. The extent to which the impairment represents the results of a single factor accounting for a wide degree of cognitive dysfunction, or is the result of the combined effects of multiple factors, has not been determined. In the present study, we analyzed data from 134 patients with AIDS and 105 HIV- controls using a recently developed analytical procedure. The results revealed that, by and large, the test variables shared a significant amount of variance related to disease status. Hence the AIDS-related influences on cognition are shared and thus cannot be considered independent. Two tests, Digit Symbol Substitution, and the primary measure of verbal free recall, had a direct relationship with the group variable (AIDS vs. controls). These results suggest that a single factor is sufficient to account for a large proportion of the AIDS-related variance on a wide variety of neuropsychological tests.

AIDS Dementia Complex↗

PubMed1999

Neurological characteristics of HIV-infected men and women seeking primary medical care.

We examined the neurological differences between human immunodeficiency virus (HIV)-infected men (n = 193) and women (n = 41) receiving primary medical care. There was no difference between men and women in the rate of HIV-related neurological syndromes (i.e. polyneuropathy, myelopathy, myopathy, HIV- dementia [HAD]). A logistic regression analysis indicated that low CD4+ cell count predicted all neurological syndromes. In addition, HAD was predicted by intravenous-drug use and lower education level, while neuropathy was associated with older age and with race. These findings indicate that there are no differences in the rate of neuropsychiatric disorders attributable to gender. The presence of other factors (e.g. drug abuse) could explain previously reported gender differences in neurological manifestations of HIV infection.

AIDS Dementia Complex↗

PubMed1999

Patterns of relative cerebral blood flow in minor cognitive motor disorder in human immunodeficiency virus infection.

Individuals infected with HIV are at risk to develop cognitive impairment during the course of their disease. Although many patients develop an HIV-associated dementia, others may develop the less severe minor cognitive motor disorder (MCMD). In this study, relative cerebral blood flow was measured with PET imaging in HIV+ MCMD patients, HIV+ control subjects, and HIV- control subjects; analyses were performed by using statistical parametric mapping. Comparing a short-term memory task versus a rest state yielded activation in superior temporal cortex, postcentral gyrus, and cerebellum in all three subject groups. Comparing long- and short-term memory tasks yielded activation throughout the frontal cortex, including BA46. Activation in this area was reduced in the HIV+ control subjects and further reduced in the MCMD+ patients. Thus, brain activation associated with lower-level, automatic processing appears normal in HIV+ MCMD+ subjects, but activation associated with effortful retrieval and organizational processes is abnormal.

Brain↗

PubMed1999

Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy.

OBJECTIVE: To determine the predictive value of plasma HIV RNA and CD4 lymphocytes for HIV-associated dementia and sensory neuropathy. METHODS: A total of 1,604 AIDS-free HIV seropositive men from the Multicenter AIDS Cohort Study were followed over a 10-year period (1985 to 1995). HIV-associated dementia and sensory neuropathy were diagnosed according to standard definitions. Baseline samples were used to measure plasma HIV RNA levels with a branched DNA assay and levels of beta2-microglobulin, CD4 lymphocyte counts, and hemoglobin levels. RESULTS: Seventy-seven patients with HIV-associated dementia and 213 patients with sensory neuropathy were identified. Baseline HIV RNA levels above 3,000 copies/mL and CD4 counts below 500 cells/mm3 were predictive of both neurologic outcomes, but neither hemoglobin, body mass index, nor beta2-microglobulin were independently predictive. After adjusting for age and level of education, individuals with baseline plasma HIV RNA >30,000 copies/mL had a relative hazard for dementia 8.5 times (p < 0.001) that of those with <3,000 copies/mL, and those with CD4 counts <200 cells/mm3 had a 3.5-fold (p = 0.003) greater hazard relative to those with CD4 counts >500 cells/mm3. Individuals with HIV RNA >10,000 copies/mL had a 2.3-fold (p = 0.008) greater hazard of sensory neuropathy than those with <500 copies/mL, and men with <750 CD4 cells/mm3 had a 1.4-fold (p = 0.03) greater hazard than those with >750 CD4 cells/mm3. CONCLUSIONS: High levels of systemic HIV replication may "drive" the initiation of neurologic disease; effective suppression of HIV may reduce the incidence of dementia and neuropathy. Levels of plasma HIV RNA and CD4 counts, determined before the initiation of antiretroviral therapy, were predictive of HIV-associated dementia and sensory neuropathy.

AIDS Dementia Complex↗

PubMed1999

Dopamine systems in human immunodeficiency virus-associated dementia.

OBJECTIVE: To provide an update of the neurobiologic basis of human immunodeficiency virus (HIV)-associated dementia (HAD), with emphasis on the relationship between dopamine (DA) system dysfunction and behavioral manifestations. BACKGROUND: HIV has a propensity to invade subcortical central nervous system areas, particularly the basal ganglia. Indeed, the core symptoms of HAD are similar to those seen in patients with frontal-striatal dysfunction, the "subcortical dementias" (e.g., Parkinson disease, Huntington disease, progressive supranuclear palsy). FINDINGS: Damage to DA neurons appears to occur in early stages of the disease. Patients with HIV have decreased levels of cerebrospinal fluid DA, and patients with HAD have a reduction of the DA metabolite homovanillic acid but a relative preservation of other neurotransmitters, suggesting a loss of DA neurons. Neuropathologic examinations have shown neuronal loss of the globus pallidus, which is less severe in the neocortex. Furthermore, extrapyramidal signs and marked hypersensitivity to DA antagonists (e.g., neuroleptics) have a propensity to develop in patients with acquired immunodeficiency syndrome. CONCLUSIONS: Neurobiologic investigations suggest that DA system dysfunction plays a critical role in the clinical manifestation of HIV infection, especially HAD. The causes of the vulnerability of this system to the infection are unknown. Understanding this mechanism is important to develop neuroprotective agents in the treatment of HAD and to design new therapies for HAD-related psychiatric symptoms.

AIDS Dementia Complex↗

PubMed1998

An examination of regional cerebral blood flow during object naming tasks.

The purpose of this study was to examine regional cerebral blood flow using positron emission tomography (PET) during the performance of tasks related to visual confrontation naming. Ten healthy, young participants were scanned twice in each of 5 conditions; blood flow was measured using standard PET [15O]-water technology. Two major findings have replicated previous studies. First, the naming of visually presented objects, whether covert or overt, requires a region of the left inferior cortex including the fusiform gyrus. Second, during overt naming, there is an increase in activity in the inferior or frontal cortex and insula as a consequence of generating speech code. These data are consistent with other studies demonstrating the importance of the inferior temporal regions for semantic processing, and the frontal cortex for word form generation.

Adult↗

PubMed1998

Independent effects of Alzheimer's disease on neuropsychological functioning.

A new analytical procedure, single common factor analysis, was carried out on the data from a relatively large sample of normals (n = 101) and patients with Alzheimer's disease (AD; n = 180) to examine the extent to which there were independent effects of disease status on different neuropsychological variables. This technique uses structural equation methods to determine what all of the variables have in common, and then controls this common factor when examining the relationship between diagnostic group and each individual test variable. To the extent that AD represents the sum of independent breakdowns of different information processing domains, then there should be sets of variables that have weak or nonexistent links to the other variables. However, the results revealed that a large proportion of the AD-related effects on test scores was shared and was not independent of the AD-related effects on other variables.

Aged↗

PubMed1998

Slowed information processing in HIV-1 disease. The Multicenter AIDS Cohort Study (MACS).

This investigation examined the effects of HIV-1 infection on speeded complex cognitive processing in a group of HIV-negative (n = 666), HIV-positive symptomatic (n = 156), and HIV-positive asymptomatic (n = 623) participants while controlling for the effects of slowed motor functioning, peripheral neuropathy, and several other putative confounds. Stroop Interference and reaction-time tasks served as anchor procedures to assess cognitive processing. The present findings suggest that HIV-1 infection is capable of compromising CNS-mediated cognitive processes (speeded processing) infringing upon their efficacy in the symptomatic stages of the disease while sparing individuals in the asymptomatic stage. The detrimental effects observed on information-processing mechanisms associated with HIV infection persisted despite the use of procedures to control for peripheral nerve integrity and other potential confounds.

AIDS Dementia Complex↗

PubMed1998

Apolipoprotein E polymorphism in Alzheimer's disease: a comparative study of two research populations from Spain and the United States.

We examined the distribution of the apolipoprotein E (APOE) polymorphism in two Caucasian populations of Alzheimer's disease (AD) patients referred to dementia clinics; one in Gerona, Spain (66 AD patients, 49 controls), and the other in Pittsburgh, Pa., USA (209 AD patients, 58 controls). The presence of the APOE*4 allele was a significant risk for developing AD in both cohorts: Gerona (odds ratio = 2.34, CI: 1.03-5.55) and Pittsburgh (odds ratio = 3.64, CI: 1.78-7.69). The proportion of AD with the APOE*4 allele was greater in the Pittsburgh cohort than in the Gerona cohort (p = 0.02). However, no statistical difference was noted between the two populations in nondemented controls (p = 0.41). These data emphasize the importance of geographical and ethnic variations in the study of APOE genotypes.

Aged↗

PubMed1998

Neurobehavioral correlates of perceived mental and motor slowness in HIV infection and AIDS.

The authors assessed 72 human immunodeficiency virus (HIV)-infected patients with a self-rating slowness scale (SRSS) concerning mental and motor slowness in their activities of daily living. In order to understand the relationship between complaints of slowness and predictor variables, the investigators developed a preliminary model using multiple regression analysis. Reports of slowness on the SRSS were independently associated with self-reported cognitive and neurological symptoms and with peripheral neurological syndromes (e.g., neuropathy, myopathy). Lesser contributions to self-perceived mental and motor slowness were found for neuropsychological measures of information processing speed, severity of the infection, depression, HIV encephalopathy, and sociodemographic factors (e.g., age, education). The relationship among the predictor variables showed that complaints of slowness reflect neurological, psychiatric/psychological, and cognitive symptomatology of the HIV infection.

AIDS Dementia Complex↗

PubMed1998

Cognition and aging in a complex work environment: relationships with performance among air traffic control specialists.

Chronological age affects the performance of demanding cognitive tasks within the aviation environment. Within the domain of air traffic control (ATC), the ability to handle simultaneous visual and auditory input, or to return to a task after a break to complete another task, is critical to success and is the sort of cognitive function most affected by age. The limited available data suggest a strong relationship between age and job performance among ATC specialists, whether measured at the time of entry into the system or during the working lifetime of a full-performance-level controller. An analysis of the distribution of the ages of controllers currently in the system, and a projection for the years 2001 and 2006, leads to the conclusion that a high proportion of the ATC work force will be at risk for displaying age-related changes in job performance efficiency over the next 10 yr. It seems important, therefore, to determine the nature and extent of the age-related cognitive changes that can occur during the lifespan of a controller (i.e., 25-55 yr of age) and how these changes may affect job performance. The results of such an analysis should aid in the design and implementation of new control systems to minimize any deleterious effects of aging on performance.

Adult↗

PubMed1997

Extrapyramidal signs in patients with probable Alzheimer disease.

OBJECTIVE: To examine whether extrapyramidal signs (EPSs) were associated with more rapid progression of Alzheimer disease (AD). DESIGN: Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: Mini-Mental State Examination score of less than 9, Blessed Dementia Rating Scale score for activities of daily living of 15 or more, institutionalization, and death using a proportional hazard model with 6 variables: overall EPSs, bradykinesia, tremors, abnormal gait, cogwheel rigidity, and postural instability. SETTING: Multidisciplinary behavioral neurology research clinic. PATIENTS: We examined the individual EPS characteristics of 164 patients with mild-moderately probable AD, free of neuroleptic medication, participating in a longitudinal study of dementia. RESULTS: Patients with AD with EPSs (n= 51 [31%]) were older (P>.001) and had lower Mini-Mental State Examination scores (P=.003) than those without EPSs at study entry. Bradykinesia was present in 35 (69%) of the 51 patients with EPSs, abnormal gait in 18 (35%), rigidity in 10 (20%), postural instability in 10 (20%), tremors in 7 (14%), and oral-mandibular dyskinesia in 2 (4%). Using proportional hazard analysis with time-dependent covariates for overall EPSs and individual EPSs, adjusted by age at study entry, education, Mini-Mental State Examination score, and Blessed Dementia Rating Scale score for activities of daily living, the development of EPSs was associated with time to institutionalization (P<.001) but not with cognitive (eg, Mini-Mental State Examination score <9) or functional (eg, Blessed Dementia Rating Scale score > or = 15) decline or death. However, when we examined severity of the EPSs, as measured by the New York University Parkinson's Disease Scale, the development of EPSs was associated with functional decline (P=.005). Of the individual EPSs, rigidity predicted death (P<.001) and institutionalization (P=.03), whereas tremors predicted functional decline (P=.02). CONCLUSIONS: In this cohort, the presence or absence of EPSs is related to time to institutionalization, but not to severe cognitive or functional impairment or death. However, when severity of the extrapyramidal phenomenon is taken into account, EPSs are related to functional decline. Further, it appears that a subgroup of patients with AD with EPSs, where cogwheel rigidity and tremors are the core signs, can have a worse outcome.

Aged↗