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Biomedical subjects

T D Marcotte

Publications and source records attributed to T D Marcotte.

17 recordsLinked to original sources
PubMed2004

A multimodal assessment of driving performance in HIV infection.

OBJECTIVE: To examine if HIV-seropositive (HIV+) individuals are at risk for impaired driving. METHODS: Sixty licensed drivers (40 HIV+, 20 HIV-) completed a neuropsychological (NP) test battery and driving assessments. Eleven HIV+ subjects were NP-impaired. Driving-related skills were assessed using 1) two driving simulations (examining accident avoidance and navigational abilities), 2) the Useful Field of View (UFOV) test, and 3) an on-road evaluation. RESULTS: HIV+ NP-impaired subjects had greater difficulty than cognitively intact subjects on all driving measures, whereas the HIV- and HIV+ NP-normal groups performed similarly. On the UFOV, the HIV+ NP-impaired group had worse performance on Visual Processing and Divided Attention tasks but not in overall risk classification. They also had a higher number of simulator accidents (1.3 vs 2.0; p = 0.03), were less efficient at completing the navigation task (3.2 vs 9.2 blocks; p = 0.001), and were more likely to fail the on-road evaluation (6 vs 36%; p = 0.02). Impairment in Executive Functioning was the strongest NP predictor of failing the on-road drive test. NP performance and both simulations independently contributed to a model predicting 48% of the variance in on-road performance. CONCLUSION: HIV+ NP-impaired individuals are at increased risk for on-road driving impairments, whereas HIV+ individuals with normal cognition are not at a significantly higher risk than HIV- subjects. Executive Functioning is most strongly associated with impaired on-road performance. Cognitive and simulator testing may each provide data in identifying driving-impaired individuals.

AIDS Dementia Complex↗
PubMed2002

Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis.

OBJECTIVE: To investigate the value of antemortem cognitive functioning in predicting postmortem evidence of HIV encephalitis (HIVE). METHODS: Thirty-nine subjects were assessed during life with a comprehensive neuropsychological battery and went on to autopsy within 18 months of testing. Cognitive impairment was determined by blind clinical ratings, based on demographically corrected test scores. Presence of HIVE was based on postmortem immunocytochemical detection of the viral protein gp41 or by measurement of HIV RNA by PCR in multiple brain areas as well as by histopathologic evidence such as microgliosis, presence of multinucleated giant cells, and myelin pallor in several brain regions. RESULTS: The sensitivity and specificity of neurocognitive impairment in detecting the occurrence of HIVE were 67 and 92%. Eighteen of 19 subjects with antemortem neurocognitive impairment had evidence of HIV-related brain disease (positive predictive value = 95%). CONCLUSION: Neuropsychological assessment can help select HIV-positive patients for treatment of CNS disease.

AIDS Dementia Complex↗
PubMed2001

Stability and course of neuropsychological deficits in schizophrenia.

BACKGROUND: Neuropsychological deficits in schizophrenia appear to predate clinical symptoms of the disease and become more pronounced at illness onset, but controversy exists about whether and when further neuropsychological progression may occur. OBJECTIVE: To identify and characterize any subset of patients who evidenced progressive neuropsychological impairment, we compared the longitudinal stability of neuropsychological functioning in schizophrenic outpatients and normal comparison subjects. METHODS: One hundred forty-two schizophrenic outpatients and 206 normal comparison subjects were given annually scheduled comprehensive neuropsychological evaluations during an average of 3 years (range, 6 months to 10 years). Clinically and demographically defined subgroups were compared, and test-retest norms were used to identify individual patients who showed unusual worsening over time. RESULTS: The schizophrenic group was neuropsychologically more impaired than the normal comparison subjects but showed comparable test-retest reliability and comparable neuropsychological stability over both short (mean, 1.6 years) and long (mean, 5 years) follow-up periods. No significant differences in neuropsychological change were found between schizophrenic subgroups defined by current age, age at onset of illness, baseline level of neuropsychological impairment, improvement or worsening of clinical symptoms, and occurrence of incident tardive dyskinesia. Norms for change also failed to show neuropsychological progression in individuals with schizophrenia. CONCLUSIONS: Neuropsychological impairment in ambulatory persons with schizophrenia appears to remain stable, regardless of baseline characteristics and changes in clinical state. Our results may not be generalizable to the minority of institutionalized poor-outcome patients.

Adult↗
PubMed2001

Long-term effects of high-dose zidovudine treatment on neuropsychological performance in mildly symptomatic HIV-positive patients: results of a randomized, double-blind, placebo-controlled investigation.

This study examined the treatment outcome of high-dose (1500 mg/day) zidovudine (AZT) on neuropsychological (NP) functioning (Trailmaking Test A & B, WAIS-R Digit Symbol, and Rey Auditory Verbal Learning Test) across a 12-month period in mildly symptomatic HIV-1 seropositive men (n = 46 at entry) enrolled in a randomized, double-blind, placebo-controlled trial (VA Cooperative Studies Program #298). Neither short-term (0-6 months) nor long-term (0-12 months) AZT administration revealed enhancement in NP performance. The results suggest that, although AZT may afford patients prophylactic benefits, protracted high-dose AZT treatment does not improve NP functioning in mildly symptomatic HIV-positive individuals.

Adult↗
PubMed2001

Detecting change: A comparison of three neuropsychological methods, using normal and clinical samples.

Detecting change in individual patients is an important goal of neuropsychological testing. However, limited information is available about test-retest changes, and well-validated prediction methods are lacking. Using a large nonclinical subject group (N = 384), we recently investigated test-retest reliabilities and practice effects on the Wechsler Adult Intelligence Scale and Halstead-Reitan Battery. Data from this group also were used to develop models for predicting follow-up test scores and establish confidence intervals around them. In this article we review those findings, examine their generalizability to new nonclinical and clinical groups, and explore the sensitivity of the prediction models to real change. Despite similarities across samples in reliability coefficients and practice effects, limits to the generalizability of prediction methods were found. Also, when multiple test measures were considered together, one or more "significant" changes were common in all (including stable) subject groups. By employing normative cut-offs that correct for this, sensitivity of the models to neurological recovery and deterioration was modest to good. More complex regression models were not more accurate than the simpler Reliable Change Index with correction for practice effects when confidence intervals for all methods were adjusted for variations in level of baseline test performance.

Journal Article↗
PubMed1999

Extending the p-plot: heuristics for multiple testing. HNRC group.

In the problem of large-scale multiple testing the p-plot is a graphically based competitor to the notoriously weak Bonferroni method. The p-plot is less stringent and more revealing in that it gives a gauge of how many hypotheses are decidedly false. The method is elucidated and extended here: the bootstrap reveals bias and sampling error in the usual point estimates, a bootstrap-based confidence interval for the gauge is given, as well as two acceptably powerful blanket tests of significance. Guidelines for use are given, and interpretational pitfalls pointed out, in the discussion of a case study linking premortem neuropsychological and postmortem neuropathologic data in an HIV cohort study.

Humans↗
PubMed1999

The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group.

HIV infection often results in neuropsychological (NP) impairment. In order to assess the impact that HIV-related NP deficits may have on automobile driving, we evaluated 68 HIV-seropositive drivers using an NP battery and two PC-based driving simulations. Thirty-two participants were classified as NP impaired; most (72%) evidenced only mild impairment, and none met criteria for HIV-associated dementia. After controlling for degree of immunosuppression and disease stage, NP-impaired participants failed a previously validated driving simulation at a much higher rate than cognitively intact participants [OR = 5.3, 95% CI (1.7, 17.0), p = .006]. Similarly, on a simulation of city driving, NP impaired participants were more likely to fail based upon the number of accidents [OR = 6.1, 95% CI (1.5, 24.6), p = .01]. Simulator performance was predicted by functioning in a number of NP domains, with NP tests accounting for 13-30% of the variance on the simulations. Although it would be premature to extrapolate these findings to impairment in on-the-road driving, they do argue for greater attention to the impact that even mild HIV-related NP deficits may have on driving skills.

AIDS Dementia Complex↗
PubMed1999

Screening for dementia: comparison of three commonly used instruments.

The sensitivity and specificity of three cognitive screening measures - the Mini-Mental State Exam (MMSE), Mattis Dementia Rating Scale (MDRS), and Neurobehavioral Cognitive Status Examination (NCSE) - were compared in a cohort of subjects with dementia as well as normal elderly individuals. Twenty-two patients met criteria for probable Alzheimer' s disease (AD), 19 for vascular dementia (VaD), and 12 were normal control subjects. The use of standard cutpoints resulted in poor to good classification accuracy for the three measures, but measurable improvement in sensitivity was obtained by adjusting the cutpoints for each measure. Discriminatory power was maximized with an MMSE cutpoint of < or = 26, an MDRS cutpoint of < or = 134, and requiring one or more NCSE subtests to be in the impaired range. Use of age and education adjusted norms resulted in good to excellent classification accuracy for the MMSE and MDRS. The NCSE subtest score pattern failed to differentiate between AD and VaD.

Aged↗
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

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↗
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↗
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

Concurrent validity of the Neurobehavioral Cognitive Status Exam subtests.

The Neurobehavioral Cognitive Status Exam (NCSE) is a screening measure that assesses numerous neuropsychological (NP) domains. Fifty-four patients completed the NCSE and common NP tests assessing similar abilities. Most subtest screens (brief items that determine whether additional testing should occur) exhibited low false negative rates, but high false positive rates, based upon performance on the follow-up metric items. Each subtest was significantly correlated with the associated NP test. However, using performance on the NP tests as the 'gold standard', the NCSE subtests classified impaired and unimpaired patients at a much lower than expected rate. The latter results draw into question the efficacy of the NCSE subtests in delineating domain-specific cognitive functioning.

Attention↗
PubMed1995

Cerebral metabolic change in patients with AIDS: report of a six-month follow-up using positron-emission tomography.

The authors examined change in cerebral metabolic function over time by using PET in HIV-infected individuals diagnosed with AIDS. Ten subjects with AIDS received [18F]2-fluoro-2-deoxy-D-glucose PET scans and completed a comprehensive neuropsychological battery. The scan and test battery were repeated after 6 months. Over time, the subjects showed increased relative basal ganglia metabolism as well as increased parietal lobe metabolism. There were no statistically significant changes in neuropsychological performance. These results suggest that PET may be more sensitive than traditional neuropsychological evaluation to subtle central nervous system changes in AIDS.

AIDS Dementia Complex↗
PubMed1994

The relationship between age and cognitive impairment in HIV-1 infection: findings from the Multicenter AIDS Cohort Study and a clinical cohort.

Previous studies have identified age as a risk factor for many neurologic disorders, and a "cerebral reserve" factor has been postulated to explain these findings. This study examined whether age represents a risk factor for HIV-1-related neuropsychological dysfunction. Subjects for study 1 were primarily asymptomatic seropositive (n = 1,066) and seronegative (n = 1,004) nonelderly male community volunteers who completed neuropsychological and reaction time measures. Data analyses revealed a significant effect for age on reaction time and timed neuropsychological measures, but no interaction between age and serostatus. Study 2, employing a similar neuropsychological battery, consisted of 76 seropositive men (29 over age 55) recruited from community outpatient clinics and 47 seronegative controls. We found serostatus and age to have main effects on a number of measures, but a trend for an effect of age-serostatus interaction on only one measure.

AIDS Dementia Complex↗