Neuropsychological changes following deep brain stimulation surgery for Parkinson's disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy.

BACKGROUND: Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target. METHODS: Neuropsychological functioning was assessed in patients with Parkinson's disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered. RESULTS: Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up. CONCLUSIONS: In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL. TRIAL REGISTRATION NUMBER: NCT00056563 and NCT01076452.

Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.

BACKGROUND: Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS: At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS: Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS: Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)

Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease.

BACKGROUND: Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS). OBJECTIVES: We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD. METHOD: Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (>70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables. RESULTS: MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages. CONCLUSIONS: Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

Long-term follow-up of pallidal deep brain stimulation in two cases of Huntington's disease.

BACKGROUND: Deep brain stimulator (DBS) implantation has been shown to be effective in the treatment of various movement disorders including Parkinson's disease, essential tremor and dystonia. However, there is limited information regarding the potential use of DBS in Huntington's disease (HD). In this study, the authors present their findings on the long-term motor and neurocognitive results of two HD patients (patient 1: 57 years, 42 cytosine-adenine guanine (CAG) repeats; patient 2: 50 years, 41 CAG repeats) who underwent staged bilateral globus pallidus interna DBS surgery. METHODS: The patients were evaluated at baseline and at five timepoints throughout a 2-year postoperative during which motoric ratings ((Unified Huntington's Disease Rating Scale), Activities of Daily Living scores (HD-ADL) and neurocognitive testing) were obtained. RESULTS: Both patients had a sustained decline in chorea 2 years after initial DBS surgery. Despite this improvement in chorea, one patient has had continuing deterioration in gait, bradykinesia and dystonia scores, which has caused his ability to perform activities of daily living to return to his baseline level of functioning prior to DBS surgery. Both patients have experienced further gradual decline in neurocognitive functioning, which appears to be independent of DBS and most likely related to disease progression. CONCLUSION: DBS implantation may be a potential treatment option for a subset of HD patients who have significant functional deficits due to chorea. However, appropriate selection of the best candidates for DBS appears to be challenging, given the difficulty in predicting disease course in HD due to its variable nature.

Video-telemedicine in a memory disorders clinic: evaluation and management of rural elders with cognitive impairment.

OBJECTIVE: Telemedicine is increasingly being used to provide consultation for healthcare in rural areas. Little work has been done with dementia although preliminary research suggests that clinical diagnosis performed via telemedicine consultation is valid. We implemented a program to provide multidisciplinary, state-of-the-art diagnosis of cognitive impairment by video-telemedicine (VTM) integrated into a clinical setting. METHODS: Patients at a rural veteran's community clinic were referred by their local provider for evaluation of memory complaints by the multidisciplinary team of the San Francisco Veterans Administration (SFVA) Memory Disorders Clinic (MDC). The evaluation was integrated into the usual clinic structure and included a neurological evaluation and neuropsychological testing by the MDC team via video assisted by a remote clinician at the community clinic. RESULTS: We evaluated 15 new patients referred to our multidisciplinary clinic. In each case, the VTM format permitted the MDC team to arrive at a working diagnosis; 12 patients with dementia, two with mild cognitive impairment, and one cognitively normal. Relevant treatment recommendations were made to the patients and caregivers. The evaluation results were discussed with providers who joined the MDC postclinic conference via VTM. In the majority of cases, recommendations were followed and there was satisfaction with VTM by providers and patients. CONCLUSIONS: VTM is emerging as an effective way to provide consultation and care to rural residents who may not have access to specialty services and can be integrated into current clinical settings.

Neuroanatomical correlates of cognitive self-appraisal in neurodegenerative disease.

Self-appraisal is a critical cognitive function, which helps us to choose tasks based on an accurate assessment of our abilities. The neural mechanisms of self-appraisal are incompletely understood, although a growing body of literature suggests that several frontal and subcortical regions are important for self-related processing. Anosognosia, or lack of awareness of one's deficits, is common in neurodegenerative dementias, offering an important window onto the brain systems involved in self-appraisal. We examined the neuroanatomical basis of self-appraisal in a mixed group of 39 individuals, including 35 with cognitive impairment due to one of several probable neurodegenerative diseases, using voxel-based morphometry and an objective, neuropsychologically-based measure of self-appraisal accuracy. Self-appraisal accuracy was correlated with tissue content in the right ventromedial prefrontal cortex (vmPFC). We hypothesize that emotional/physiological processing carried out by vmPFC is an important factor mediating self-appraisal accuracy in dementia.

Peripheral biomarkers do not correlate with cognitive impairment in highly active antiretroviral therapy-treated subjects with human immunodeficiency virus type 1 infection.

Neuropsychological (NP) impairments in human immunodeficiency virus (HIV)-infected individuals remain high despite the introduction of highly active antiretroviral therapy (HAART). We sought to determine whether or not a monocyte gene expression profile along with other peripheral factors would correlate with neuropsychological impairment among HIV-infected individuals. Forty-four HIV-1-seropositive subjects (HIV+) on HAART and 11 HIV-1-seronegative controls (HIV-) had NP testing and blood drawn for monocyte gene expression analysis. All HIV+ subjects were assessed for CD4 counts, apolipoprotein E (ApoE) genotype, viral load, and plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14). NP scores were normalized to age, gender, and education. Twenty-five percent of HIV+ individuals showed abnormal NP testing results (> 1.5 SD below normal in two domains). HIV+ individuals had deficits in attention/working memory, verbal learning, and information processing speed compared to HIV- controls. There was no correlation between overall NP impairment and plasma viral load, level of education, age, ethnic diversity, sCD14, plasma LPS, CD4 cell count, ApoE genotype, or years of infection. However, greater years of infection had worse visual learning performance. sCD14 and CD4 nadir positively correlated with information processing speed and fine motor skills, respectively. LPS correlated with viral load but not cognitive impairment. Monocyte gene expression confirmed a chronic inflammatory profile that correlated with viral load but not cognition. No blood index or profile was associated with overall NP impairment.

Standardised measurement of self-awareness deficits in FTD and AD.

BACKGROUND: Diminished ability to perceive one's own impairments, whether cognitive or social, is common in dementia, in particular frontotemporal dementia (FTD), where 'lack of insight' is listed as a core diagnostic feature. Yet, there is no currently accepted method for measuring insight in dementia. The most commonly used methods, which involve comparing patients' opinions of their level of impairment with the opinions of care givers or close family members, are subjective and require the participation of a knowledgeable informant. Here, the authors introduce a new method that allows objective quantification of an individual's awareness of their cognitive abilities and relies upon objective bedside testing. METHODS: The authors administered several tests of everyday, real-world functions to patients with FTD (n=10) and Alzheimer's disease (AD, n=10) and to control subjects (n=10). Prior to the tasks, participants were asked to predict their performance using a percentile-based rating system. They were also asked to estimate their performance after task completion. Differences between their self-rated and actual performances were calculated. RESULTS: Whereas the control group showed very little discrepancy between pretest predictions, post-task estimates and actual performance (mean difference of 3.9 percentile points for prediction/3.0 percentile points for post-task estimate), both patient groups overpredicted and overestimated their performance, with a significantly greater discrepancy for FTD (49.0/54.3 percentile points) than AD (27.2/28.3 percentile points). DISCUSSION: Failures of insight and self-awareness of cognitive dysfunction can be objectively measured in dementia without the assistance of an informant, which will facilitate further study of this key component of higher cognitive functioning.

Measures of learning, memory and processing speed accurately predict smoking status in short-term abstinent treatment-seeking alcohol-dependent individuals.

AIM: Chronic cigarette smoking appears to adversely affect several domains of neurocognition in those with alcohol use disorders (AUDs). The primary goal of this study was to identify which measures commonly used to assess neurocognition in AUDs accurately predict smoking status of individuals seeking treatment of alcohol dependence. METHODS: Treatment-seeking alcohol-dependent participants (ALC; n = 92) completed a comprehensive neuropsychological battery after 33 ± 9 days of abstinence. Measures significantly different between smoking and non-smoking ALC were entered as predictors in binary logistic regression and discriminant analysis models, with smoking status as the dependent variable. RESULTS: Smoking ALC performed significantly worse than non-smoking ALC on measures assessing processing speed, auditory-verbal and visuospatial learning and memory. Using these measures as predictors, a logistic regression model accurately classified 91% of smokers and non-smokers into their respective groups overall and accounted for 68% of the variance in smoking status. The discriminant analysis confirmed the findings from the logistic regression. In smoking ALC, smoking chronicity was inversely related to performance on multiple measures after controlling for lifetime alcohol consumption. CONCLUSIONS: Measures of processing speed, learning and memory robustly predicted the smoking status of ALC with high sensitivity and specificity during early abstinence. The results identified specific measures within a comprehensive neurocognitive battery that discriminated smoking and non-smoking alcohol-dependent individuals with a high sensitivity and specificity. The association of greater smoking chronicity and poorer performance on multiple measures after control for alcohol consumption suggests that chronic smoking adds an additional burden to neurocognitive function in those with alcohol dependence.

Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial.

CONTEXT: Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. OBJECTIVE: To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006. INTERVENTION: Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists. MAIN OUTCOME MEASURES: The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. RESULTS: Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage. CONCLUSION: In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056563.

Comparing Self to Peers in Percentile Equivalents during Cognitive Testing: More Accurate Self-Appraisal Estimates are Associated with Greater Ability and Less Reliance on the Representativeness Heuristic.

OBJECTIVE: For individuals with neurologic disorders, self-awareness of cognitive impairment is associated with indicators of better treatment course and clinical outcomes. Lower self-appraisal accuracy has been found to be associated with impairments in neuropsychological test performance, but individuals who perform unusually well may be equally vulnerable to inaccurate self-ratings. The mixed pattern of cognitive strengths and deficits in individuals with neurologic disorders complicates development of formal metrics for assessment of self-awareness. It remains unclear to what extent distortions in self-appraisal represent a deficit associated with impaired cognitive functioning, or a normal reliance on the "representativeness-heuristic" that results in greater bias in self-ratings in both strong and poor performers. METHOD: The present study investigated these hypotheses using a common-metric approach (Rothlind, Dukarm, and Kraybill, 2016). Participants included 199 adults, recruited from community sources, including healthy adult volunteers and individuals at-risk for neuropsychological impairment secondary to human immunodeficiency virus (HIV) positive status or active heavy alcohol consumption or both. Immediately following completion of standardized neuropsychological tests, participants estimated their own performance percentile ranking. RESULTS: Both high and low-scoring examinees displayed a conservative bias in ranking their own neuropsychological performance. However, lower scores were associated with least accurate self-appraisals overall. CONCLUSION: Findings suggest that cognitive impairments are associated with lower accuracy in self-rating of cognitive ability, but also that normal biases complicate interpretation of self-appraisal ratings across the spectrum of neuropsychological functioning. The importance of recognizing these biases in clinical research and practice is emphasized, and directions for future research are discussed.

The relationships of sociodemographic factors, medical, psychiatric, and substance-misuse co-morbidities to neurocognition in short-term abstinent alcohol-dependent individuals.

Co-morbidities that commonly accompany those afflicted with an alcohol use disorder (AUD) may promote variability in the pattern and magnitude of neurocognitive abnormalities demonstrated. The goal of this study was to investigate the influence of several common co-morbid medical conditions (primarily hypertension and hepatitis C), psychiatric (primarily unipolar mood and anxiety disorders), and substance use (primarily psychostimulant and cannabis) disorders, and chronic cigarette smoking on the neurocognitive functioning in short-term abstinent, treatment-seeking individuals with AUD. Seventy-five alcohol-dependent participants (ALC; 51+/-9 years of age; three females) completed comprehensive neurocognitive testing after approximately 1 month of abstinence. Multivariate multiple linear regression evaluated the relationships among neurocognitive variables and medical conditions, psychiatric, and substance-use disorders, controlling for sociodemographic factors. Sixty-four percent of ALC had at least one medical, psychiatric, or substance-abuse co-morbidity (excluding smoking). Smoking status (smoker or nonsmoker) and age were significant independent predictors of cognitive efficiency, general intelligence, postural stability, processing speed, and visuospatial memory after age-normed adjustment and control for estimated pre-morbid verbal intelligence, education, alcohol consumption, and medical, psychiatric, and substance-misuse co-morbidities. Results indicated that chronic smoking accounted for a significant portion of the variance in the neurocognitive performance of this middle-aged AUD cohort. The age-related findings for ALC suggest that alcohol dependence, per se, was associated with diminished neurocognitive functioning with increasing age. The study of participants who demonstrate common co-morbidities observed in AUD is necessary to fully understand how AUD, as a clinical syndrome, affects neurocognition, brain neurobiology, and their changes with extended abstinence.

Chronic cigarette smoking and heavy drinking in human immunodeficiency virus: consequences for neurocognition and brain morphology.

Alcohol use disorders (AUD) and chronic cigarette smoking are common among individuals with human immunodeficiency virus infection (HIV). Concurrent AUD in HIV is related to greater abnormalities in brain morphology and neurocognition than either condition alone. However, the potential influence of chronic smoking on brain morphology and neurocognition in those concurrently afflicted with AUD and HIV has not been examined. The goal of this retrospective analysis was to determine if chronic smoking affected neurocognition and brain morphology in a subsample of HIV-positive non-treatment-seeking heavy drinking participants (HD+) from our earlier work. Regional volumetric and neurocognitive comparisons were made among age-equivalent smoking HD+(n=17), nonsmoking HD+ (n=27), and nonsmoking HIV-negative light drinking controls (n=27) obtained from our original larger sample. Comprehensive neuropsychological assessment evaluated multiple neurocognitive domains of functioning and for potential psychiatric comorbidities. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and sulcal and ventricular cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance images. The main findings were (1) smoking HD+ performed significantly worse than nonsmoking HD+ on measures of auditory-verbal (AV) learning, AV memory, and cognitive efficiency; (2) relative to controls, smoking HD+ demonstrated significantly lower neocortical GM volumes in all lobes except the occipital lobe, while nonsmoking HD+ showed only lower frontal GM volume compared with controls; (3) in the HD+ group, regional brain volumes and neurocognition were not influenced by viremia, highly active antiretroviral treatment, or Center for Disease Control symptom status, and no interactions were apparent with these variables or smoking status. Overall, the findings suggested that the direct and/or indirect effects of chronic cigarette smoking created an additional burden on the integrity of brain neurobiology and neurocognition in this cohort of HIV-positive heavy drinkers.

Assessment of Self-Awareness of Cognitive Function: Correlations of Self-Ratings with Actual Performance Ranks for Tests of Processing Speed, Memory and Executive Function in Non-Clinical Samples.

OBJECTIVE: For individuals with neurologic disorders, self-awareness of cognitive impairment is associated with improved treatment course and clinical outcome. However, methods for assessment of levels of self-awareness are limited, and most require collateral information, which may not be readily available. Although distortions in self-awareness are most often associated with low cognitive ability, the frequently mixed pattern of cognitive strengths and deficits in individuals with neurologic disorders complicates assessment. The present study explores relationships between actual test performance and self-ratings, utilizing a brief probe administered during testing. The "common-metric" approach solicits self-appraisal ratings in percentile equivalents and capitalizes on available normative data for specific standardized neuropsychological tests to allow direct comparisons. METHOD: A convenience sample of 199 adults recruited from community sources participated in this study, including healthy adults and neuropsychologically "at-risk" volunteers who were HIV positive and/or endorsing heavy current alcohol consumption. Immediately following completion of standardized neuropsychological tests, participants estimated their own percentile ranking. RESULTS: Across study groups, participant's estimates of their own percentile rank were modestly correlated with actual performance ranking. Highest correlations were obtained for tests of learning, memory and conceptual reasoning, and executive function, with smaller correlations for simple tests of motor and psychomotor speed. CONCLUSIONS: The study reveals normal biases affecting the self-appraisal during standardized testing, and suggests that a common-metric approach for assessing self-appraisal may play a role in establishing clinical thresholds and identifying and quantifying reductions in insight in persons with neuropsychological deficits.

Neuropsychological functioning in posttraumatic stress disorder and alcohol abuse.

Studies have shown differences in neuropsychological functioning between groups with posttraumatic stress disorder (PTSD) and control participants. Because individuals with PTSD often have a history of comorbid alcohol abuse, the extent to which an alcohol confound is responsible for these differences remains a concern. The current study compares neuropsychological testing scores in 4 groups of veterans with and without PTSD (PTSD+ and PTSD-, respectively) and with and without a history of alcohol abuse (ETOH+ and ETOH-, respectively): n for PTSD+/ETOH- = 30, n for PTSD+/ETOH- = 37, n for PTSD-/ETOH+ = 30, and n for PTSD-/ETOH- = 31. Results showed that PTSD, when alcohol, educational level, vocabulary, and depression are controlled for, was associated with decreased verbal memory, attention, and processing speed performance. Alcohol abuse history was associated with decreased visual memory performance. By controlling for alcohol and depression, the authors can more conclusively demonstrate that verbal memory and attention differences are associated with PTSD.

A comparison of neurocognitive function in nonsmoking and chronically smoking short-term abstinent alcoholics.

Approximately 70-90% of individuals in North America seeking treatment for alcoholism are chronic smokers. A growing body of evidence suggests chronic cigarette smoking alone adversely affects neurocognition in adults. However, few studies on the neurocognitive function of short-term abstinent alcoholics have specifically considered the potential effects of chronic cigarette smoking. In this study, 20 nonsmoking recovering alcoholics (nsRA) and 22 actively smoking recovering alcoholics (sRA) participants, matched on age and education, were contrasted on a comprehensive neurocognitive battery after 34+/-9 days of abstinence. nsRA were superior to sRA on measures of auditory-verbal learning and memory, processing speed, cognitive efficiency, and static postural stability. These group differences were not a function of group disparities in age, education, estimated premorbid verbal intelligence, lifetime alcohol consumption, or other measured comorbid psychiatric or medical factors. In sRA, longer smoking duration was negatively correlated with executive skills, visuospatial learning, general cognitive efficiency, and static postural stability. These results indicate that greater consideration of the potential neurobiological effects of current chronic smoking on neurocognitive functioning is warranted in studies of alcoholism and other conditions where smoking is a common comorbid factor.

Abnormal contingent negative variation in HIV patients receiving antiretroviral therapy.

The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virally suppressed patients and controls on neuropsychological measures of psychomotor speed, selective attention and mental flexibility. These results suggest that antiretroviral therapy may not be effective in protecting cortical and subcortical structures against HIV-related neuropathology, regardless of immune function. However, the benefits of antiretroviral therapy on immune function appear to facilitate neurocognitive performance.

Abnormal CNV in chronic heavy drinkers.

OBJECTIVE: We used the contingent negative variation (CNV), a slow negative shift in the human electroencephalogram, to investigate the effects of heavy chronic alcohol use on frontal lobe function. METHODS: Event-related potentials (ERPs) were recorded from 30 heavy drinkers (HD) and 30 age-, sex-, and education-matched light or non-drinkers (LD), using a classical two-stimulus reaction time (RT) paradigm. Structural magnetic resonance images and neuropsychological tests were also administered. RESULTS: The amplitude of the late CNV was significantly reduced in HD relative to light drinkers. Moreover, diminished CNV amplitudes in HD appear to be closely related to the amount of recent alcohol consumption. There were no significant differences in neuropsychological measures of frontal lobe function and frontal lobe volume between light and HD. However, in HD, reduced late CNV amplitudes were associated with decreased frontal lobe gray matter volume and poor performance on the Trail Making Test B. In LD but not in HD, late CNV amplitude correlated positively with RT, suggesting that the late CNV reflects some aspect of motor and cognitive preparation. CONCLUSIONS: The inverse relationships between frontal lobe gray matter volume, performance on the Trail Making Test B, and late CNV amplitude in HD suggest that the ERP abnormalities observed in the current study may be indices of alcohol-related damage to the frontal lobe. The lack of a significant relationship between CNV amplitude and RT in HD suggests that chronic heavy alcohol use may disrupt response preparation.

Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes.

OBJECTIVES: Our objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial. METHODS: Patients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinson's Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function. RESULTS: Motor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] -16.4 to -10.8; p < 0.001) and STN (42.5 to 29.7; 95% CI -15.8 to -9.4; p < 0.001); improvements were similar between targets and stable over time (p = 0.59). Health-related quality of life improved at 6 months on all subscales (all p values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients (p = 0.01); other neurocognitive measures showed gradual decline overall. CONCLUSIONS: The beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. Neurology® 2012;79:55-65.

Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans.

BACKGROUND: Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure. METHODS: Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002 and 2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus. RESULTS: GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p< or =0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure. CONCLUSIONS: These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later.