Abstract Objective This paper summarizes the findings of the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project and offers a roadmap for future research. Methods The NP-NUMBRS project represents the largest and most comprehensive co-normed neuropsychological battery to date for native Spanish-speaking healthy adults from the U.S. (California/Arizona)-Mexico borderland region (N = 254; ages 19–60 years). These norms provide demographic adjustments for tests across numerous domains (i.e., verbal fluency, processing speed, attention/working memory, executive function, episodic memory [learning and delayed recall], visuospatial, and fine motor skills). Conclusions This project: 1) shows that the NP-NUMBRS norms consistently outperformed previously published norms for English-speaking non-Hispanic (White and African-American) adults in identifying impairment; 2) explores the role of Spanish-English bilingualism in test performance; and 3) provides support for the diagnostic validity of these norms in detecting HIV-associated neurocognitive impairment. Study limitations include the limited assessment of sociocultural variables and generalizability (e.g., other Latina/o populations, age limit [19 − 60 years]). Future research is needed to: 1) investigate these norms with U.S.-dwelling Spanish-speakers of non-Mexican heritage and other clinical subpopulations; 2) expand coverage of cognitive domains (e.g. language, visuospatial); 3) develop large normative datasets for children and older Latina/o populations; 4) examine how sociocultural factors impact performance (e.g., bilingualism, acculturation); 5) investigate these norms’ diagnostic and ecological validity; and 6) develop norms for neurocognitive change across time. It is hoped that the NP-NUMBRS norms will aid researchers and clinicians working with U.S.-dwelling Spanish-speakers from the U.S.-Mexico borderland to conduct research and evidence-based neuropsychological evaluations in a more culturally responsive and ethical manner.

Growing evidence points to persistent neurological injury in chronic HIV infection. It remains unclear whether chronically HIV-infected individuals on combined antiretroviral therapy (cART) develop progressive brain injury and impaired neurocognitive function despite successful viral suppression and immunological restoration. In a longitudinal neuroimaging study for the HIV Neuroimaging Consortium (HIVNC), we used tensor-based morphometry to map the annual rate of change of regional brain volumes (mean time interval 1.0 ± 0.5 yrs), in 155 chronically infected and treated HIV+ participants (mean age 48.0 ± 8.9 years; 83.9% male) . We tested for associations between rates of brain tissue loss and clinical measures of infection severity (nadir or baseline CD4+ cell count and baseline HIV plasma RNA concentration), HIV duration, cART CNS penetration-effectiveness scores, age, as well as change in AIDS Dementia Complex stage. We found significant brain tissue loss across HIV+ participants, including those neuro-asymptomatic with undetectable viral loads, largely localized to subcortical regions. Measures of disease severity, age, and neurocognitive decline were associated with greater atrophy. Chronically HIV-infected and treated individuals may undergo progressive brain tissue loss despite stable and effective cART, which may contribute to neurocognitive decline. Understanding neurological complications of chronic infection and identifying factors associated with atrophy may help inform strategies to maintain brain health in people living with HIV.

OBJECTIVE:The structure of neurocognition is explored by examining the neurocognitive domains underlying comprehensive neuropsychological assessment of cognitively healthy individuals.METHOD:Exploratory factor analysis was conducted on the adult normative dataset of an expanded Halstead-Reitan Battery (eHRB), comprising Caucasian and African American participants. The factor structure contributions of the original HRB, eHRB expansion, and Wechsler intelligence scales were compared. Demographic effects were examined on composite factor scores calculated using confirmatory factor analysis.RESULTS:The full eHRB had an eight-factor structure, with latent constructs including: 'working memory', 'fluency', 'verbal episodic memory', 'visuospatial cognition' (visuospatial memory and problem solving), 'perceptual-motor speed' (speed for processing visual/tactile material and hand-motor execution), 'perceptual attention' (attention to sensory-perceptual information), 'semantic knowledge' (knowledge acquired through education and culturally-based experiences), and 'phonological decoding' (grapheme-phoneme processing essential for sounding-out words). 'Perceptual-motor speed' and 'perceptual attention' were most negatively associated with age, whereas 'semantic knowledge' and 'phonological decoding' were most resistant to aging. 'Semantic knowledge' showed the greatest dependence on demographic background, including education and ethnicity. Gender differences in cognitive performances were negligible across all domains except 'phonological decoding' with women slightly outperforming men. The original HRB contributed four neurocognitive domains, the eHRB expansion three domains, and the Wechsler scales one additional domain but with restructuring of verbal factors.CONCLUSION:Eight neurocognitive domains underlie performance of healthy cognitive individuals during comprehensive neuropsychological assessment. These domains serve as framework for understanding the constructs measured by commonly-used neuropsychological tests and may represent the structure of neurocognition.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N -acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG ( R 2 0.179, p < 0.001) as well as MCP-1 and MI in FWM ( R 2 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 ( R 2 0. 075, p = 0.01) and IP-10 ( R 2 0.106, p = 0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM ( R 2 0.224, p < 0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals.

Cognitive impairment and brain injury are common in people with HIV/AIDS, even when viral replication is effectively suppressed with combined antiretroviral therapies (cART). Metabolic and structural abnormalities may promote cognitive decline, but we know little about how these measures relate in people on stable cART. Here we used tensor-based morphometry (TBM) to reveal the 3D profile of regional brain volume variations in 210 HIV+ patients scanned with whole-brain MRI at 1.5 T (mean age: 48.6 +/- 8.4 years; all receiving cART). We identified brain regions where the degree of atrophy was related to HIV clinical measures and cerebral metabolite levels assessed with magnetic resonance spectroscopy (MRS). Regional brain volume reduction was linked to lower nadir CD4+ count, with a 1-2% white matter volume reduction for each 25-point reduction in nadir CD4+. Even so, brain volume measured by TBM showed no detectable association with current CD4+ count, AIDS Dementia Complex (ADC) stage, HIV RNA load in plasma or cerebrospinal fluid (CSF), duration of HIV infection, antiretroviral CNS penetration-effectiveness (CPE) scores, or years on cART, after controlling for demographic factors, and for multiple comparisons. Elevated glutamate and glutamine (Glx) and lower N-acetylaspartate (NAA) in the frontal white matter, basal ganglia, and mid frontal cortex - were associated with lower white matter, putamen and thalamus volumes, and ventricular and CSF space expansion. Reductions in brain volumes in the setting of chronic and stable disease are strongly linked to a history of immunosuppression, suggesting that delays in initiating cART may result in imminent and irreversible brain damage. (C) 2013 The Authors. Published by Elsevier Inc.

Objectives: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). Methods: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). Results: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm3 (30% vs 47% in remaining subgroups). Conclusions: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.

This paper presents a decision theoretic ranking system that incorporates both explicit and implicit feedback. The system has a model that predicts, given all available data at query time, different interactions a person might have with search results. Possible interactions include relevance labelling and clicking. We define a utility function that takes as input the outputs of the interaction model to provide a real valued score to the user’s session. The optimal ranking is the list of documents that, in expectation under the model, maximizes the utility for a user session. The system presented is based on a simple example utility function that combines both click behavior and labelling. The click prediction model is a Bayesian generalized linear model. Its notable characteristic is that it incorporates both weights for explanatory features and weights for each querydocument pair. This allows the model to generalize to unseen queries but makes it at the same time flexible enough to keep in a ‘memory’ where the model should deviate from its feature based prediction. Such a click-predicting model could be particularly useful in an application such as enterprise search, allowing on-site adaptation to local documents and user behaviour. The example utility function has a parameter that controls the tradeoff between optimizing for clicks and optimizing for labels. Experimental results in the context of enterprise search show that a balance in the tradeoff leads to the best NDCG and good (predicted) clickthrough.

Through mass-digitization projects and with the use of OCR technologies, digitized books are becoming available on the Web and in digital libraries. The unprecedented scale of these efforts, the unique characteristics of the digitized material as well as the unexplored possibilities of user interactions make full-text book search an exciting area of information retrieval (IR) research. Emerging research questions include: How appropriate and effective are traditional IR models when applied to books? What book specific features (e.g., back-of-book index) should receive special attention during the indexing and retrieval processes? How can we tackle scalability? In order to answer such questions, we developed an experimental platform to facilitate rapid prototyping of a book search system as well as to support large-scale tests. Using this system, we performed experiments on a collection of 10 000 books, evaluating the efficiency of a novel multi-field inverted index and the effectiveness of the BM25F retrieval model adapted to books, using book-specific fields.

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).

Following the publication of the third edition Wechsler scales (i.e., WAIS-III and WMS-III), demographically corrected norms were made available in the form of a computerized scoring program (i.e., WAIS-III/WMS-III/WIAT-II Scoring Assistant). These norms correct for age, gender, ethnicity, and education. Since then, four new indexes have been developed: the WAIS-III General Ability Index, the WMS-III Delayed Memory Index, and the two alternate Immediate and Delayed Memory Indexes. The purpose of this study was to develop demographically corrected norms for the four new indexes using the standardization sample and education oversample from the WAIS-III and WMS-III. These norms were developed using the same methodology as the demographically corrected norms made available in the WAIS-III/WMS-III/WIAT-II Scoring Assistant.

OBJECTIVE:Some excess morbidity and mortality in Alzheimer caregivers (CGs) may be related to chronic activation of the sympatho-adrenal-medullary (SAM) system. Authors tested the efficacy of an in-home respite intervention to reduce peripheral markers of SAM activation and psychological distress in spousal caregivers of patients with Alzheimer disease.METHODS:Caregivers were classified as Vulnerable (n = 27) or Non-Vulnerable (n = 28). Vulnerable CGs were those with a severe mismatch between caregiving demand and help received in the preceding 6 months. CGs had plasma catecholamine levels sampled at rest and in response to a stressor (speech task) before and 1 month after a 2-week in-home respite intervention. Self-reported symptoms of anxiety and depression were also obtained.RESULTS:ANOVA revealed a group x treatment interaction: At the 1-month follow-up, plasma epinephrine declined significantly in the vulnerable caregivers who received respite, but rose in those who were wait-listed. No effect was found for norepinephrine, heart rate, blood pressure, or psychological symptoms.CONCLUSION:Findings suggest that an in-home respite program may reduce SAM activation independent of psychological symptoms. To the extent that sympathetic activation mediates pathophysiological events, these results suggest an approach that may reduce morbidity and mortality in certain caregivers.

This chapter discusses the influence of demographic on Wechsler Adult Intelligence Scale III (WAIS-III) and Wechsler Memory Scale-III (WMS-III). The presentation of demographic influences on WAIS-WMS performance focuses on two issues of relevance to clinicians, and especially to clinical neuropsychologists. First, it focuses on the six cognitive constructs identified by recent confirmatory factor analyses of the joint WAIS-WMS battery. It is likely that these six factor scores will be increasingly seen as the most useful core data generated by the combined battery, gradually supplanting less precise indices and subtest scores. Second, it focuses on the relevance of demographic effects for the development and use of test norms. Particularly when cognitive tests scores are used for neurodiagnostic purposes, specificity should be as constant as possible across all segments of the normal population. The data from the WAIS-WMS standardization samples indicate that performance on all six cognitive factors are significantly related to education and ethnicity, in addition to age, some sex effects are noted as well. These demographic effects are not peculiar to the versions of the WAIS-WMS batteries. Similar findings have been reported for earlier versions of these tests and many other neuropsychological tests.

Although abuse of cocaine or methamphetamine usually takes place in the context of heavy drinking, there is little information on the effects of such substance use comorbidity on brain perfusion. We explored similarities and differences in the effects of these two drugs in combination with alcohol on brain function using SPECT. Global and regional cerebral blood flow (CBF) were examined in 7 abstinent cocaine-dependent alcoholics (CDA; mean age = 39.2 yr, S.D. = 9.2 yr), 7 abstinent methamphetamine-dependent alcoholics (MDA; mean age = 36.8 yr, S.D. = 5.0 yr), and 7 non-alcoholic/non-stimulant abusing controls (NAC; mean age = 37.3 yr, S.D. = 9.6 yr). MDA had significantly lower global CBF than CDA who, in turn, were significantly lower than NAC. In addition, CDA had abnormal perfusion in the superior posterior frontal region compared to NAC; while MDA did not display specific regional deficits. Therefore, it appears that cocaine alters the relationship between global and regional CBF in alcoholics, while methamphetamine does not.

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.

Cognitive and motor function are known to deteriorate with the hypoxia accompanying high altitude, posing a substantial challenge to the efficient operation of high altitude industrial and scientific projects. To evaluate the effectiveness of enriching room air oxygen by 6% at 5,000 m altitude in ameliorating such deficits, 24 unacclimatized subjects (16 males, 8 females; mean age 37.8, range 20 to 47) underwent neuropsychological testing in a specially designed facility at 3,800 m that can simulate an ambient 5,000 m atmosphere and 6% enrichment at 5,000 m. Each subject was tested in both conditions in a randomized, double-blinded fashion. The 2-h test battery of 16 tasks assessed various aspects of motor and cognitive performance. Compared with simulated breathing air at 5,000 m, oxygen enrichment resulted in higher arterial oxygen saturations (93.0 vs. 81.6%), quicker reaction times, improved hand-eye coordination, and more positive sense of well-being (on 6 of 16 scales), each significant at the p < 0.05 level. Other aspects of neuropsychological function were not significantly improved by 6% additional oxygen.

Cognitive and motor function are known to deteriorate with the hypoxia accompanying high altitude, posing a substantial challenge to the efficient operation of high altitude industrial and scientific projects. To evaluate the effectiveness of enriching room air oxygen by 6% at 5000 m altitude in ameliorating such deficits, 24 unacclimatized subjects (16 males, 8 females; mean age 37.8, range 20 to 47) underwent neuropsychological testing in a specially designed facility at 3800 m that can simulate an ambient 5000 m atmosphere and 6% enrichment at 5000 m. Each subject was tested in both conditions in a randomized, double-blinded fashion. The 2-h test battery of 16 tasks assessed various aspects of motor and cognitive performance. Compared with simulated breathing air at 5000 m, oxygen enrichment resulted in higher arterial oxygen saturations (93.0 vs. 81.6%), quicker reaction times, improved hand-eye coordination, and more positive sense of well-being (on 6 of 16 scales), each significant at the p < 0.05 level. Other aspects of neuropsychological function were not significantly improved by 6% additional oxygen.