Age-related, multivariate associations between white matter microstructure and behavioral performance in three executive function domains.

The executive function (EF) domains of working memory (WM), response inhibition (RI), and set shifting (SS) show maturational gains and are linked to neuroimaging-measured brain changes. This study explored ways in which maturation-linked differences in EF abilities are systematically associated with white matter microstructural differences from adolescence into young adulthood. Diffusion tensor imaging (DTI) and nine neurocognitive tests were collected from 120 healthy subjects ages 12-24. Analyses across the white matter skeleton were performed, focusing on fractional anisotropy (FA). Data were 'fused' using a multivariate technique (CCA+jICA), producing four independent components (ICs) depicting white matter FA values that covaried with test performance. Correlations between age and IC loading coefficients identified three EF-DTI profiles that may change developmentally. In one, SS performance was linked to greater reliance on the FA of ventral brain tracts, and less on dorsal tracts with age. In another, white matter microstructure was related to a pattern of strong WM and weak SS that became more pronounced with age. A final IC revealed that younger individuals with low RI and high WM/SS skills typically matured out of this cognitive imbalance, underscored by white matter changes with age. These novel multivariate results begin to emphasize the complexity of brain structure-cognition relationships in adolescents and young adults.

Depression predicts cognitive and functional decline one month after coronary artery bypass graft surgery (Neuropsychiatric Outcomes After Heart Surgery study).

BACKGROUND: Prior research on cognitive and functional outcomes after coronary artery bypass graft (CABG) surgery has largely explored these two domains in isolation. In this study, we assess baseline depression and cognition as risk factors for decline in the Clinical Dementia Rating Sum-of-Boxes (CDR-SB) 1 month post-CABG surgery, which a combined measure of cognition and function. DESIGN: The Neuropsychiatric Outcomes After Heart Surgery study is a prospective observational cohort study. SETTING: A tertiary care, academic center. PARTICIPANTS: Of a total study sample of 148 patients undergoing CABG surgery, 124 (83.8%) completed 1-month follow-up assessment. Mean age was 66.3, 32 (25.8%) female and 112 (90.3%) White. MEASUREMENTS: Cognition, function, and depression were assessed on semi-structured clinical interviews. Cognitive and functional status were defined using CDR-SB; mild or major depression was defined by the Hamilton Depression Rating Scale. Additionally, neuropsychological battery was performed at baseline. RESULTS: CDR-SB decline occurred in 18 (14.5%) subjects. Older age, depression, baseline CDR-SB, and postoperative delirium were associated with 1-month decline on univariate analysis. Older age (OR 1.1 [1.0-1.2]) and depression (OR 6.2 [1.1-35.0]) remained significant on multivariate regression. In separate models, baseline performance on visual Wechsler memory scale (delayed), Hopkins verbal learning test (immediate and delayed), controlled oral word fluency test, and Trails B predicted CDR-SB decline. CONCLUSION: Roughly one in seven patients experienced CDR-SB decline 1 month after CABG surgery. Also, preoperative depression deserves recognition for being a predictor of CDR-SB decline one month post-CABG.

Neuropsychiatric symptoms and cognitive abilities over the initial quinquennium of Parkinson disease.

OBJECTIVE: To determine the evolution of numerous neuropsychiatric symptoms and cognitive abilities in Parkinson disease from disease onset. METHODS: Prospectively collected, longitudinal (untreated, disease onset to year 5), observational data from Parkinson's Progression Markers Initiative annual visits was used to evaluate prevalence, correlates, and treatment of 10 neuropsychiatric symptoms and cognitive impairment in Parkinson disease participants and matched healthy controls. RESULTS: Of 423 Parkinson disease participants evaluated at baseline, 315 (74.5%) were assessed at year 5. Eight neuropsychiatric symptoms studied increased in absolute prevalence by 6.2-20.9% at year 5 relative to baseline, and cognitive impairment increased by 2.7-6.2%. In comparison, the frequency of neuropsychiatric symptoms in healthy controls remained stable or declined over time. Antidepressant and anxiolytic/hypnotic use in Parkinson disease were common at baseline and increased over time (18% to 27% for the former; 13% to 24% for the latter); antipsychotic and cognitive-enhancing medication use was uncommon throughout (2% and 5% of patients at year 5); and potentially harmful anticholinergic medication use was common and increased over time. At year 5 the cross-sectional prevalence for having three or more neuropsychiatric disorders/cognitive impairment was 56% for Parkinson disease participants versus 13% for healthy controls, and by then seven of the examined disorders had either occurred or been treated at some time point in the majority of Parkinson disease patients. Principal component analysis suggested an affective disorder subtype only. INTERPRETATION: Neuropsychiatric features in Parkinson disease are common from the onset, increase over time, are frequently comorbid, and fluctuate in severity.

Depression Predicts Delirium After Coronary Artery Bypass Graft Surgery Independent of Cognitive Impairment and Cerebrovascular Disease: An Analysis of the Neuropsychiatric Outcomes After Heart Surgery Study.

OBJECTIVE: Although depression is a known risk factor for delirium after coronary artery bypass graft (CABG) surgery, it is unclear whether this risk is independent of delirium risk attributable to cognitive impairment or cerebrovascular disease. This study examines depression, mild cognitive impairment (MCI), and cerebrovascular disease as post-CABG delirium risk factors. METHODS: This prospective observational cohort study was performed in a tertiary-care academic hospital. Subjects were without dementia and undergoing CABG surgery. Preoperative cognitive assessment included Clinical Dementia Rating and neuropsychological battery; depression was assessed using Depression Interview and Structured Hamilton. Baseline intracranial stenosis was evaluated by transcranial Doppler of bilateral middle cerebral arteries (MCAs). Study psychiatrists assessed delirium on postoperative days 2-5 using the Confusion Assessment Method. RESULTS: Our analytic sample comprised 131 subjects (average age: 65.8 ± 9.2years, 27% women). MCI prevalence was 24%, preoperative depression 10%, lifetime depression 35%, and MCA stenosis (≥50%) 28%. Sixteen percent developed delirium. Multivariate analysis revealed that age, MCI (odds ratio [OR]: 5.1; 95% confidence interval [CI]: 1.3-20.1), and preoperative depression (OR: 9.9; 95% CI: 1.3-77.9)-but not lifetime depression-predicted delirium. MCA stenosis and severity predicted delirium in univariate but not multivariate analysis. Right MCA stenosis severity predicted delirium severity, but left-sided stenosis severity did not. CONCLUSION: We established that the risk of delirium attributable to depression extends beyond the potential moderating influence of cognitive impairment and cerebrovascular disease alone. Even mild depression and cognitive impairment before CABG deserve recognition for their effect on post-CABG cognitive health.

The effect of age and smoking on the hippocampus and memory in late middle age.

From middle age the hippocampus atrophies at an accelerating rate. Factors that further this acceleration may hasten memory decline and the onset of memory disorder. We studied associations between smoking history, age, ApoE e4 genotype, vascular risk factors, hippocampal volume, and cognition in 67 middle-aged subjects (mean age = 56 years) who were offspring of parents with dementia. Subjects underwent isotropic T1-weighted 3 T MRI brain scanning with FreeSurfer volumetric data extraction for the hippocampus, a neuropsychological assessment battery, extensive medical data collection, and ApoE genotyping. ApoE e4, vascular risk variables, and alcohol history were unrelated to hippocampal volume. Hippocampal volume correlated negatively with age and positively with memory performance, but not with global cognition. Aging diminished hippocampal volume by 0.52% per year. Female subjects (only two males smoked) with a heavy smoking history (≥ 9.5 pack-years; n = 11) exhibited hippocampal volumes that were 7.4% smaller than the volumes of females (n = 37) with a light or no smoking history. In our sample by late middle age, a history of moderate to heavy smoking is associated with hippocampal atrophy equivalent to 12 years of aging. Since only a small number of subjects within the sample have a smoking history, validation of this finding in larger samples is desirable.

Cognition among individuals along a spectrum of increased risk for Parkinson's disease.

INTRODUCTION: Several characteristics associated with increased risk for Parkinson's disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration. METHODS: Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations)). Inclusion criteria enriched the RBD and hyposmia cohorts, but not the NMC cohort, with individuals with dopamine transporter binding deficit. Baseline neuropsychological performance was compared, and analyses were adjusted for age, sex, education, and depression. RESULTS: The RBD cohort performed significantly worse than the hyposmia and NMC cohorts on Symbol Digit Modality Test (mean (SD) 32.4 (9.16) vs. 41.8 (9.98), p = 0.002 and vs. 45.2 (10.9), p<0.001) and Judgment of Line Orientation (11.3 (2.36) vs.12.9 (1.87), p = 0.004 and vs. 12.9 (1.87), p<0.001). The RBD cohort also performed worse than the hyposmia cohort on the Montreal Cognitive Assessment (25.5 (4.13) vs. 27.3 (1.71), p = 0.02). Hyposmics did not differ from PD or NMC cohorts on any cognitive test score. CONCLUSION: Among individuals across a spectrum of risk for PD, cognitive function is worse among those with the characteristic most strongly associated with future risk of PD or dementia with Lewy bodies, namely RBD.

Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial.

This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally mediated cognitive functions, as well as quality of life and global function in healthy older participants. One hundred twenty-three participants aged 75 years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, or placebo daily for 12 weeks. The primary outcome measure was the change in z-score for 6 prefrontal executive function tasks over 12 weeks (PEF6). Neither dose of guanfacine improved PEF6 z-score relative to placebo. The rate of mean change (95% confidence interval) in PEF6 z-score over 12 weeks was 0.270 (0.159, 0.380) for placebo, compared with 0.121 (0.011, 0.232) for guanfacine 0.1 mg (p = 0.06, compared to placebo) and 0.213 (0.101, 0.324) for 0.5 mg (p = 0.47). Neither dose of guanfacine improved the quality of life or global function relative to placebo. Among common adverse events, only dry mouth was significantly more frequent on guanfacine compared to placebo. Guanfacine failed to ameliorate prefrontal cognitive function in older individuals, who were cognitively normal for age.

Relationship between fMRI response during a nonverbal memory task and marijuana use in college students.

Marijuana (MJ) is widely used among college students, with peak use between ages 18-22. Research suggests memory dysfunction in adolescent and young adult MJ users, but the neural correlates are unclear. We examined functional magnetic resonance imaging (fMRI) response during a memory task among college students with varying degrees of MJ involvement. Participants were 64 college students, ages 18-20, who performed a visual encoding and recognition task during fMRI. MJ use was ascertained for 3 months prior to scanning; 27 individuals reported past 3-month MJ use, and 33 individuals did not. fMRI response was modeled during encoding based on whether targets were subsequently recognized (correct encoding), and during recognition based on target identification (hits). fMRI response in left and right inferior frontal gyrus (IFG) and hippocampal regions of interest was examined between MJ users and controls. There were no group differences between MJ users and controls on fMRI response during encoding, although single sample t-tests revealed that MJ users failed to activate the hippocampus. During recognition, MJ users showed less fMRI response than controls in right hippocampus (Cohen's d = 0.55), left hippocampus (Cohen's d = 0.67) and left IFG (Cohen's d = 0.61). Heavier MJ involvement was associated with lower fMRI response in left hippocampus and left IFG. This study provides evidence of MJ-related prefrontal and hippocampal dysfunction during recognition memory in college students. These findings may contribute to our previously identified decrements in academic performance in college MJ users and could have substantial implications for academic and occupational functioning.

A New Measure for Neural Compensation Is Positively Correlated With Working Memory and Gait Speed.

Neuroimaging studies suggest that older adults may compensate for declines in brain function and cognition through reorganization of neural resources. A limitation of prior research is reliance on between-group comparisons of neural activation (e.g., younger vs. older), which cannot be used to assess compensatory ability quantitatively. It is also unclear about the relationship between compensatory ability with cognitive function or how other factors such as physical exercise modulates compensatory ability. Here, we proposed a data-driven method to semi-quantitatively measure neural compensation under a challenging cognitive task, and we then explored connections between neural compensation to cognitive engagement and cognitive reserve (CR). Functional and structural magnetic resonance imaging scans were acquired for 26 healthy older adults during a face-name memory task. Spatial independent component analysis (ICA) identified visual, attentional and left executive as core networks. Results show that the smaller the volumes of the gray matter (GM) structures within core networks, the more networks were needed to conduct the task (r = -0.408, p = 0.035). Therefore, the number of task-activated networks controlling for the GM volume within core networks was defined as a measure of neural compensatory ability. We found that compensatory ability correlated with working memory performance (r = 0.528, p = 0.035). Among subjects with good memory task performance, those with higher CR used fewer networks than subjects with lower CR. Among poor-performance subjects, those using more networks had higher CR. Our results indicated that using a high cognitive-demanding task to measure the number of activated neural networks could be a useful and sensitive measure of neural compensation in older adults.

Longitudinal Effects of Alcohol Consumption on the Hippocampus and Parahippocampus in College Students.

BACKGROUND: The hazardous effects of alcohol consumption on both the hippocampus and memory have been well established. However, the longitudinal effects of ethanol on the developing brain and related consequences on memory are not well explored. Given the above, we investigated the longitudinal effects of college drinking on hippocampal volume in emerging college adults. METHODS: Data were derived from the longitudinal Brain and Alcohol Research with College Students study. A subset of 146 freshmen (mean age at baseline = 18.5 years) underwent brain magnetic resonance imaging scans at baseline and 24 months later. Four drinking-related measures derived from monthly surveys were reduced to a single alcohol use index using principal component analysis. Gray matter volumetric change (GMV-c) data were derived using a longitudinal pipeline. Voxelwise hippocampal/para-hippocampal GMV-c associations with the drinking index were derived using a multiple regression framework within SPM12. Supplementary associations were assessed between GMV-c and memory scores computed from the California Verbal Learning Test-II (assessed at the end of the study), and between GMV-c and total alcohol-induced memory blackouts. RESULTS: Larger alcohol use index was associated with an accelerated GMV decline in the hippocampus/para-hippocampus. Also, larger hippocampal volume decline was associated with poorer memory performance and more memory blackouts. CONCLUSIONS: Our study extends prior cross-sectional literature by showing that a heavier drinking burden while in college is associated with greater hippocampal GMV decline that is in turn associated with poorer memory scores, all of which could ultimately have a significant impact on student success.

Cognition and the course of prodromal Parkinson's disease.

BACKGROUND: Prospective data on cognition in prodromal Parkinson's disease are limited. The objectives of this study were to assess in prodromal PD (1) if baseline cognition predicts conversion to clinical PD, (2) if baseline dopamine transporter binding predicts longitudinal changes in cognition, and (3) if impaired olfaction predicts future cognitive decline. METHODS: Prodromal participants were 136 hyposmic individuals enrolled in the Parkinson Associated Risk Study. We examined baseline neuropsychological test performance in PD converters versus nonconverters and the association between baseline dopamine transporter binding and change in cognition. An additional 73 normosmic individuals were included in analyses of the relationship between hyposmia and cognitive decline. RESULTS: In prodromal participants, baseline cognitive scores did not significantly predict conversion, but converters performed numerically worse on 5 of the 6 cognitive domains assessed, with the greatest differences in executive function/working memory (0.68 standard deviation lower) and global cognition (0.64 standard deviation lower). Lower baseline dopamine transporter binding predicted greater future decline in processing speed/attention (P = 0.02). Hyposmia predicted greater future decline in language (P = 0.005) and memory (P = 0.01) abilities. CONCLUSIONS: Given hyposmia in the general population predicts cognitive decline, the role of cognition in predicting conversion in prodromal PD needs to be assessed in large cohorts followed long-term. The dopamine system may be associated with changes in processing speed/attention in individuals at risk for PD. © 2017 International Parkinson and Movement Disorder Society.

Heavy Drinking in College Students Is Associated with Accelerated Gray Matter Volumetric Decline over a 2 Year Period.

Background: Heavy and/or harmful alcohol use while in college is a perennial and significant public health issue. Despite the plethora of cross-sectional research suggesting deleterious effects of alcohol on the brain, there is a lack of literature investigating the longitudinal effects of alcohol consumption on the adolescent brain. We aim to probe the longitudinal effects of college drinking on gray matter change in students during this crucial neurodevelopmental period. Methods: Data were derived from the longitudinal Brain and Alcohol Research in College Students (BARCS) study of whom a subset underwent brain MRI scans at two time points 24 months apart. Students were young adults with a mean age at baseline of about 18.5 years. Based on drinking metrics assessed at both baseline and followup, subjects were classified as sustained abstainers/light drinkers (N = 45) or sustained heavy drinkers (N = 84) based on criteria established in prior literature. Gray matter volumetric change (GMV-c) maps were derived using the longitudinal DARTEL pipeline as implemented in SPM12. GMV-c maps were then subjected to a 1-sample and 2-sample t-test in SPM12 to determine within- and between-group GMV-c differences in drinking groups. Supplementary between-group differences were also computed at baseline only. Results: Within-group analysis revealed significant decline in GMV in both groups across the 2 year followup period. However, tissue loss in the sustained heavy drinking group was more significant, larger per region, and more widespread across regions compared to abstainers/light drinkers. Between-group analysis confirmed the above and showed a greater rate of GMV-c in the heavy drinking group in several brain regions encompassing inferior/medial frontal gyrus, parahippocampus, and anterior cingulate. Supplementary analyses suggest that some of the frontal differences existed at baseline and progressively worsened. Conclusion: Sustained heavy drinking while in college was associated with accelerated GMV decline in brain regions involved with executive functioning, emotional regulation, and memory, which are critical to everyday life functioning. Areas of significant GMV decreases also overlapped largely with brain reward and stress systems implicated in addictive behavior.

Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease.

OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aß], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition. Additionally, longitudinal structural MRI and DAT scan data were included. Univariate analyses were run initially, with false discovery rate = 0.2, to select biomarker variables for inclusion in multivariable longitudinal mixed-effect models. RESULTS: By year 3, cognitive impairment was diagnosed in 15-38% participants depending on the criteria applied. Biomarkers, some longitudinal, predicting cognitive impairment in multivariable models were: (1) dopamine deficiency (decreased caudate and putamen DAT availability); (2) diffuse, cortical decreased brain volume or thickness (frontal, temporal, parietal, and occipital lobe regions); (3) co-morbid Alzheimer's disease Aß amyloid pathology (lower CSF Aß 1-42); and (4) genes (COMT val/val and BDNF val/val genotypes). CONCLUSIONS: Cognitive impairment in PD increases in frequency 50-200% in the first several years of disease, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease plaque pathology, and genetic factors.

Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients.

Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively "normal" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24 h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24 h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE ε4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.

Composite impulsivity-related domains in college students.

Impulsivity is a complex, multidimensional construct with prior theoretically and empirically derived characterizations of impulsivity-related behaviors varying considerably among studies. We assessed college students (N = 440) longitudinally with five impulsivity-related self-reported assessments and two computerized behavioral measures. Using a combination of exploratory and confirmatory factor analysis (CFA), we derived then validated several composite impulsivity-related domains (CIRDs). These factors replicated, in large part, findings from a previous study conducted by our group in an independent sample that used a similar analytical approach. The four CIRDs derived in current study are: 'Impulsive action', 'Approach/Appetite Motivation', 'Impulsivity/Compulsivity' and 'Experience and thrill seeking/Fearlessness'. Subsequent psychometric analyses found these CIRDs were relatively stable over the two-year period. Moreover, multiple regression analysis found that CIRD profiles associated with clinical and behavioral characteristics including anxiety, depression, attention deficit hyperactivity disorder and substance use symptomology. Overall, our data suggest that empirically-derived CIRDs have potential for organizing previous impulsivity-related constructs into a more naturalistic framework where distinct constructs are often expressed together in the same individuals. This framework might facilitate future research of neuropsychiatric disorder risk and etiology.

Probing Implicit Learning in Obsessive-Compulsive Disorder: Moderating Role of Medication on the Weather Prediction Task.

Deficits in implicit learning, a process by which knowledge is acquired accretively through practice independent of conscious awareness, have been implicated in Obsessive-Compulsive Disorder (OCD). The weather-prediction task (WPT) was used to assess implicit learning in 26 unmedicated patients with OCD and 23 healthy controls. An additional analysis compared these two groups with 25 medicated patients with OCD. In the comparison of unmedicated patients with healthy controls there was a subtle but statistically significant group-by-block interaction. Patients with OCD showed slower improvement in performance during the middle phase of learning. In a three-group comparison, there was no main effect of group; in post-hoc tests, medicated patients with OCD differed from unmedicated patients and were not different from healthy controls. Unmedicated patients with OCD have a subtle deficit in implicit learning in the WPT. This may be mitigated by pharmacotherapy, although prospective studies would be required to confirm this conclusion.

Utility of pretransplant psychological measures to predict posttransplant outcomes in liver transplant patients: a systematic review.

OBJECTIVE: Evaluation of liver transplant (LT) candidacy involves psychosocial evaluation to ensure appropriate organ allocation. However, the utility of pre-LT psychiatric and neuropsychological factors in predicting posttransplant outcomes remains uncertain. We reviewed current evidence on the prognostic value of pre-LT psychological factors for outcomes after LT. METHOD: We conducted a systematic review of studies with adult LT recipients that investigate the relationship between pre-LT psychiatric and neuropsychological variables and posttransplant outcomes. We searched Ovid, MEDLINE, PsycINFO, EMBASE/Scopus, Cochrane Controlled trials register and Web of Science (January 1975 to May 2015) for longitudinal, peer-reviewed studies of at least 20 subjects and written in English. RESULTS: The 19 studies included in this review are heterogeneous in population, prognosis and duration of follow-up (from 20days to more than 3 years). Findings on the prognostic value of pre-LT depression or anxiety on post-LT outcomes are mixed, though depression appears to predict lower quality of life (QOL). Pre-LT suicidal thoughts in particular are associated with post-LT depression. High submissiveness may predict rejection within 20days of LT, and low conscientiousness is associated with greater nonadherence. Whereas pre-LT cognitive performance has not been shown to predict survival, poorer performance may predict poorer QOL after LT. CONCLUSION: Further studies are needed to examine this important element of LT candidacy evaluation. Studies should evaluate psychiatric factors in large samples, include systematic evaluations by mental health clinicians and explore broader neuropsychological domains in predicting posttransplant outcomes.

Cognition in individuals at risk for Parkinson's: Parkinson associated risk syndrome (PARS) study findings.

OBJECTIVES: The Parkinson Associated Risk Syndrome Study identified a cohort of healthy adults with hyposmia and dopamine transporter binding reduction to characterize individuals at risk for Parkinson's disease (PD). We describe the cognitive profile of this cohort. METHODS: Individuals older than 50 y without PD were recruited. Two hundred twenty-five completed cognitive testing and were included in the final analysis. A neuropsychological test battery was administered and normative scores created for global cognition, memory, executive function/working memory, processing speed/attention, visuospatial abilities, and language domains. Other non-motor symptoms (constipation, depression, anxiety, and rapid eye movement sleep behavior disorder) were assessed through questionnaires. RESULTS: Individuals with both hyposmia and reduced dopamine transporter binding (n = 38) had lower mean scores for global cognition, executive function/working memory, and memory compared with all other participants (n = 187). In separate multivariate logistic regression models, lower global cognition (odds ratio, 1.97, P = 0.004), and specifically executive function/working memory (odds ratio, 1.84, P = 0.004) scores were associated with membership in the hyposmia with dopamine transporter reduction group. Combining hyposmia with relative impairment on specific cognitive domains increased the odds of dopamine transporter binding reduction compared with hyposmia alone, with the greatest increase in odds for hyposmia plus executive function/working memory relative impairment (68% increase in odds from 4.14 to 6.96). CONCLUSION: Changes in global cognitive abilities, and specifically executive function/working memory, are present in individuals at risk for PD. Combining non-motor features, including cognition, improves prediction of dopamine transporter binding reduction.

Cognitive and functional status predictors of delirium and delirium severity after coronary artery bypass graft surgery: an interim analysis of the Neuropsychiatric Outcomes After Heart Surgery study.

BACKGROUND: Cognitive and functional impairment increase risk for post-coronary artery bypass graft (CABG) surgery delirium (PCD), but how much impairment is necessary to increase PCD risk remains unclear. METHODS: The Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study is a prospective, observational cohort study of participants undergoing elective CABG surgery. Pre-operative cognitive and functional status based on Clinical Dementia Rating (CDR) scale and neuropsychological battery are assessed. We defined mild cognitive impairment (MCI) based on either (1) CDR global score 0.5 (CDR-MCI) or (2) performance 1.5 SD below population means on any cognitive domain on neurocognitive battery (MCI-NC). Delirium was assessed daily post-operative day 2 through discharge using the confusion assessment method (CAM) and delirium index (DI). We investigate whether MCI - either definition - predicts delirium or delirium severity. RESULTS: So far we have assessed 102 participants (mean age 65.1 ± 9; male: 75%) for PCD. Twenty six participants (25%) have MCI-CDR; 38 (62% of those completing neurocognitive testing) met MCI-NC criteria. Fourteen participants (14%) developed PCD. After adjusting for age, sex, comorbidity, and education, MCI-CDR, MMSE, and Lawton IADL score predicted PCD on logistic regression (OR: 5.6, 0.6, and 1.5, respectively); MCI-NC did not (OR [95% CI]: 11.8 [0.9, 151.4]). Using similarly adjusted linear regression, MCI-CDR, MCI-NC, CDR sum of boxes, MMSE, and Lawton IADL score predicted delirium severity (adjusted R(2): 0.26, 0.13, 0.21, 0.18, and 0.32, respectively). CONCLUSIONS: MCI predicts post-operative delirium and delirium severity, but MCI definition alters these relationships. Cognitive and functional impairment independently predict post-operative delirium and delirium severity.

RBANS Norms based on the Relationship of Age, Gender, Education, and WRAT-3 Reading to Performance within an Older African American Sample.

OBJECTIVE: Due to factors including differences in educational opportunity, African Americans and Caucasians frequently differ on cognitive tests creating diagnostic error risks. Such differences have been found on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and preliminary norms based on a small sample of African Americans have been generated. In a larger sample of community-dwelling older African Americans, we explored sources of variance including age, gender, common medical conditions, years of education, and reading level to generate norms stratified on the most relevant bases. METHOD: Three hundred and fifty-five African Americans aged 55+ and living independently completed the RBANS and health, education, and psychosocial interviews. RESULTS: Hypertension and type 2 diabetes were unrelated to overall RBANS performance once age and education were accounted for. Age, education, and WRAT-3 Reading score (a proxy for scholastic attainment) were independent predictors of RBANS performance. Females performed better on List Learning, Story Memory, Fluency, Coding, List Recall, and List Recognition; males were superior on Line Orientation and Picture Naming. CONCLUSIONS: In addition to generating norms stratified by age, we provide descriptive statistics grouped by age and education, and by age and WRAT-3 Reading grade level, to provide clinicians with the opportunity to tailor their interpretation of scores based upon perceived best fit for their patient. Regression formulas are provided to address gender differences. To complement the standard index norms, we provide norms for alternative indexes representing additional an factor structure of cognitive domains.