J. Cobb Scott

Neurocognitive effects of methamphetamine: a critical review and meta-analysis.

This review provides a critical analysis of the central nervous system effects of acute and chronic methamphetamine (MA) use, which is linked to numerous adverse psychosocial, neuropsychiatric, and medical problems. A meta-analysis of the neuropsychological effects of MA abuse/dependence revealed broadly medium effect sizes, showing deficits in episodic memory, executive functions, information processing speed, motor skills, language, and visuoconstructional abilities. The neuropsychological deficits associated with MA abuse/dependence are interpreted with regard to their possible neural mechanisms, most notably MA-associated frontostriatal neurotoxicity. In addition, potential explanatory factors are considered, including demographics (e.g., gender), MA use characteristics (e.g., duration of abstinence), and the influence of common psychiatric (e.g., other substance-related disorders) and neuromedical (e.g., HIV infection) comorbidities. Finally, these findings are discussed with respect to their potential contribution to the clinical management of persons with MA abuse/dependence.

A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is associated with regional alterations in brain structure and function that are hypothesized to contribute to symptoms and cognitive deficits associated with the disorder. We present here the first systematic meta-analysis of neurocognitive outcomes associated with PTSD to examine a broad range of cognitive domains and describe the profile of cognitive deficits, as well as modifying clinical factors and study characteristics. This report is based on data from 60 studies totaling 4,108 participants, including 1,779 with PTSD, 1,446 trauma-exposed comparison participants, and 895 healthy comparison participants without trauma exposure. Effect-size estimates were calculated using a mixed-effects meta-analysis for 9 cognitive domains: attention/working memory, executive functions, verbal learning, verbal memory, visual learning, visual memory, language, speed of information processing, and visuospatial abilities. Analyses revealed significant neurocognitive effects associated with PTSD, although these ranged widely in magnitude, with the largest effect sizes in verbal learning (d = -.62), speed of information processing (d = -.59), attention/working memory (d = -.50), and verbal memory (d =-.46). Effect-size estimates were significantly larger in treatment-seeking than community samples and in studies that did not exclude participants with attention-deficit/hyperactivity disorder, and effect sizes were affected by between-group IQ discrepancies and the gender composition of the PTSD groups. Our findings indicate that consideration of neuropsychological functioning in attention, verbal memory, and speed of information processing may have important implications for the effective clinical management of persons with PTSD. Results are further discussed in the context of cognitive models of PTSD and the limitations of this literature.

Longer term improvement in neurocognitive functioning and affective distress among methamphetamine users who achieve stable abstinence

Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little in the way of data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent, and 58 used MA at least once during the interval period. A total of 38 non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long-term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use MA were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities than the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.

Visual Attention Deficits are Associated with Driving Accidents in Cognitively-Impaired HIV-Infected Individuals.

Previous research has found HIV-associated neuropsychological (NP) dysfunction to be associated with impaired driving skills. To determine whether specific impairments in visual attention impart an increased accident risk, we assessed 21 HIV seronegative (HIV-) and 42 seropositive (HIV+) participants on NP tests and the Useful Field of View (UFOV), a computerized test of visual attention. HIV+ participants performed significantly worse than the HIV- participants on the UFOV, particularly on the Divided Attention subtest. Poor UFOV performance was associated with higher accident rates in the past year, with a trend for NP impairment to also predict more accidents. The highest number of accidents occurred in the group with a “high risk” UFOV designation and NP impairment; this category correctly classified 93% of HIV+ participants as to who did, and did not, have an accident. Clinicians should attend to visual attention as well as general cognitive status in estimating which patients are at risk for impaired driving.

Predictive validity of demographically adjusted normative standards for the HIV Dementia Scale

The aim of the current study was to develop and validate demographically adjusted normative standards for the HIV Dementia Scale (HDS). Given the association between demographic variables and the HDS summary score, demographically adjusted normative standards may enhance the classification accuracy of the HDS. Demographically adjusted normative standards were derived from a sample of 182 seronegative healthy participants and were subsequently applied to a sample of 135 HIV-1 seropositive individuals with multidisciplinary case conference diagnoses of HIV-1-associated neurocognitive disorders (e.g., HIV-1-associated dementia and minor-cognitive/motor disorder) in proportions consistent with published epidemiologic reports. In the normative sample, age and education (and their interaction) emerged as the only demographic factors significantly associated with the HDS. In comparison to the traditional HDS cut score (raw score total ≤10), use of the demographically adjusted normative standards significantly improved the sensitivity (from 17.2% to 70.7%, respectively) and overall classification accuracy (increasing the odds ratio from 3 to approximately 6) of the HDS for identifying participants with HIV-1-associated neurocognitive disorders. The application of demographically adjusted normative standards on the HDS improves the clinical applicability and accuracy of this cognitive screening measure in the detection of HIV-1-associated neurocognitive disorders.

Lower Cognitive Reserve Among Individuals with Syndromic HIV-Associated Neurocognitive Disorders (HAND)

HIV-seropositive individuals with low cognitive reserve are at high risk for developing HIV-associated neurocognitive disorders (HAND). The present study evaluated the hypothesis that cognitive reserve would also play a unique role in the expression of everyday functioning complications among those with HAND (i.e., syndromic versus subsyndromic impairment). Eighty-six individuals with HIV infection were evaluated; 53 individuals evidenced normal neurocognitive performance, 16 had subsyndromic HAND (i.e., asymptomatic neurocognitive impairment), and 17 were diagnosed with syndromic HAND based on a comprehensive neurobehavioral evaluation. Cognitive reserve represented a combined score including years of education, estimated verbal IQ, and highest occupational attainment. The groups were comparable (e.g. demographics), and the HAND groups had similar rates of global neurocognitive impairment. The syndromic HAND group evidenced lower reserve scores relative to both other groups, suggesting that individuals with lower reserve may be less able to effectively counteract their neurocognitive impairment to maintain independence in daily living activities than HIV-infected individuals with high cognitive reserve.

The contribution of cognition and spasticity to driving performance in multiple sclerosis

OBJECTIVE To examine the independent and combined impact of cognitive dysfunction and spasticity on driving tasks involving high cognitive workload and lower-limb mobility in persons with multiple sclerosis (MS). DESIGN Single-visit cohort study. SETTING Clinical research center. PARTICIPANTS Participants included 17 drivers with MS and 14 referent controls. The group with MS exhibited a broad range of cognitive functioning and disability. Of the 17 patients with MS, 8 had significant spasticity in the knee used to manipulate the accelerator and brake pedals (based on the Modified Ashworth Scale). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES A brief neuropsychologic test battery and 2 driving simulations. Simulation 1 required participants to maintain a constant speed and lane position while attending to a secondary task. Simulation 2 required participants to adjust their speed to accelerations and decelerations of a lead car in front of them. RESULTS Patients with MS showed greater variability in lane position (effect size, g=1.30), greater difficulty in maintaining a constant speed (g=1.25), and less ability to respond to lead car speed changes (g=1.85) compared with controls. Within the MS group, in a multivariate model that included neuropsychologic and spasticity measures, cognitive functioning was the strongest predictor of difficulty in maintaining lane position during the divided attention task and poor response time to lead car speed changes, whereas spasticity was associated with reductions in accuracy of tracking the lead car movements and speed maintenance. CONCLUSIONS In this preliminary study, cognitive and physical impairments associated with MS were related to deficits in specific components of simulated driving. Assessment of these factors may help guide the clinician regarding the types of driving behaviors that would put patients with MS at an increased risk for an automobile crash.

Executive dysfunction and neuropsychiatric symptoms predict lower health status in essential tremor.

ObjectiveTo evaluate the hypothesis that increased neuropsychiatric distress and cognitive impairment are associated with lower perceived health status in essential tremor (ET). BackgroundMany patients with ET experience nonmotor complications, including lower perceived health status and poor health-related quality of life, which are associated with tremor severity, age, and personality factors. No studies, however, have examined the potential contribution of neuropsychiatric symptoms and cognitive deficits to health status in ET. MethodForty-five patients with ET underwent comprehensive neurologic and neuropsychologic evaluations, including self-report measures of physical and psychosocial health status (ie, the Sickness Impact Profile) and neuropsychiatric distress (ie, the Profile of Mood States). ResultsA series of hierarchical multiple regressions showed that after considering the effects of ET disease severity, lower vigor, and deficits in executive functions were independently predictive of poorer physical health status, whereas increased symptoms of depression were uniquely associated with lower psychosocial health status. ConclusionsFindings indicate that reduced vigor (ie, apathy), executive deficits, and depression are important predictors of poorer perceived health status in ET. Given the prevalence of such nonmotor symptoms, these data highlight the potential value of considering neuropsychiatric and neurocognitive assessments in the management of patients with ET.

Action (Verb) Fluency Predicts Dependence in Instrumental Activities of Daily Living in Persons Infected With HIV-1

Inspired by the hypothesized neural dissociation between the retrieval of nouns and verbs, several studies now support the construct validity of Action (verb) Fluency as a measure of frontostriatal systems function. Relative to traditional noun- and letter-cued verbal fluency tests, Action Fluency is more sensitive to HIV-1-associated neuropsychological impairment, which may reflect inefficiencies engaging motor representations during action retrieval in this population. Accordingly, impaired Action Fluency might adversely impact instrumental activities of daily living (IADL) by disrupting the production and organization of script-based action schemas upon which successful IADL performance depends. The present study thus sought to evaluate the ecological validity of Action Fluency as a predictor of IADL among persons with HIV-1 infection. Action, Letter (FAS), and Noun (animal) fluency were compared in 21 HIV-1-infected participants with self-reported IADL dependence relative to 76 demographically comparable HIV-1-infected participants who reported no IADL declines. Results revealed significant between-group differences in Action and Letter Fluency, but not Noun Fluency. Action Fluency achieved an overall hit rate of 76% and was more sensitive than Letter Fluency in classifying IADL dependent participants. Individuals with impaired Action Fluency performance had a fivefold risk of concurrent IADL dependence as compared to those who performed within normal limits. Findings suggest that Action Fluency may possess incremental ecological validity in the identification of HIV-1-associated neurocognitive disorders. The HNRC is supported by Center award MH 62512 from the National Institute of Mental Health. The research described was also supported by grants DA12065 and MH59745 from the National Institutes of Health. Note that, the views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government. The authors thank Jennifer Marquie Beck for her assistance with data coding.

Cognitive Mechanisms of Switching in HIV-Associated Category Fluency Deficits

HIV infection is associated with deficits in category fluency, but the underlying cognitive mechanisms of such impairments have not been determined. Considering the preferential disruption of the structure and function of frontostriatal circuits in HIV disease, the present study evaluated the hypothesis that HIV-associated category fluency deficits are driven by impaired switching. Study participants were 96 HIV-infected individuals and 43 demographically comparable healthy comparison volunteers who were administered a standard measure of animal fluency and an alternating category fluency task (i.e., fruits and furniture) in a randomized order. Consistent with prior research on letter fluency, HIV infection was associated with greater impairments in switching, but not semantic clustering within the animal fluency task. Moreover, a significant interaction was observed whereby the HIV-associated deficits in switching were exacerbated by the explicit demands of the alternating fluency task. Across both fluency tasks, switching demonstrated generally small correlations with standard clinical measures of executive functions, working memory, and semantic memory. Collectively, these findings suggest that HIV-associated category fluency deficits are driven by switching impairments and related cognitive abilities (e.g., mental flexibility), perhaps reflecting underlying neuropathology within prefrontostriatal networks.