Objectives: To refine mild cognitive impairment (MCI) diagnostic criteria, we examined progression to dementia using two approaches to identifying MCI. Methods: A total of 1203 Framingham Heart Study participants were classified at baseline as cognitively normal or MCI (overall and four MCI subtypes) via conventional Petersen/Winblad criteria (single cognitive test impaired per domain, >1.5 SD below expectations) or Jak/Bondi criteria (two tests impaired per domain, >1 SD below norms). Cox proportional hazards models were constructed to examine the association between each MCI definition and incident dementia. Results: The Petersen/Winblad criteria classified 34% of participants as having MCI while the Jak/Bondi criteria classified 24% as MCI. Over a mean follow-up of 9.7 years, 58 participants (5%) developed incident dementia. Both MCI criteria were associated with incident dementia [Petersen/Winblad: hazards ratio (HR) = 2.64; p-value=.0002; Jak/Bondi: HR=3.30; p-value <.0001]. When both MCI definitions were included in the same model, only the Jak/Bondi definition remained statistically significantly associated with incident dementia (HR=2.47; p-value=.008). Multi-domain amnestic and single domain non-amnestic MCI subtypes were significantly associated with incident dementia for both diagnostic approaches (all p-values <.01). Conclusions: The Jak/Bondi MCI criteria had a similar association with dementia as the conventional Petersen/Winblad MCI criteria, despite classifying ~30% fewer participants as having MCI. Further exploration of alternative methods to conventional MCI diagnostic criteria is warranted. (JINS, 2016, 22, 937–943)

Objectives: Use of appropriate face processing strategies is important for facial emotion recognition, which is known to be impaired in schizophrenia (SZ) and bipolar disorder (BD). There is preliminary evidence of abnormalities in the use of face processing strategies in the former, but there has been no explicit attempt to assess face processing in patients with BD. Methods: Twenty-eight BD I, 28 SZ, and 28 healthy control participants completed tasks assessing featural and configural face processing. The facial inversion effect was used as a proxy of second order configural face processing and compared to featural face processing performance (which is known to be relatively less affected by facial inversion). Results: Controls demonstrated the usual second-order inversion pattern. In the BD group, the absence of a second-order configural inversion effect in the presence of a disproportionate bias toward a featural inversion effect was evident. Despite reduced accuracy performance in the SZ group compared to controls, this group unexpectedly showed a normal second-order configural accuracy inversion pattern. This was in the context of a reverse inversion effect for response latency, suggesting a speed-versus-accuracy trade-off. Conclusions: To our knowledge, this is the first study to explicitly examine and contrast face processing in BD and SZ. Our findings indicate a generalized impairment on face processing tasks in SZ, and the presence of a second-order configural face processing impairment in BD. It is possible that these face processing impairments represent a catalyst for the facial emotion recognition deficits that are commonly reported in the literature. (JINS, 2016, 22, 652–661)

Background: The degree of overlap between schizophrenia (SCZ) and affective psychosis (AFF) has been a recurring question since Kraepelin’s subdivision of the major psychoses. Studying nonpsychotic relatives allows a comparison of disorder-associated phenotypes, without potential confounds that can obscure distinctive features of the disorder. Because attention and working memory have been proposed as potential endophenotypes for SCZ and AFF, we compared these cognitive features in individuals at familial high-risk (FHR) for the disorders. Methods: Young, unmedicated, first-degree relatives (ages, 13–25 years) at FHR-SCZ (n=41) and FHR-AFF (n=24) and community controls (CCs, n=54) were tested using attention and working memory versions of the Auditory Continuous Performance Test. To determine if schizotypal traits or current psychopathology accounted for cognitive deficits, we evaluated psychosis proneness using three Chapman Scales, Revised Physical Anhedonia, Perceptual Aberration, and Magical Ideation, and assessed psychopathology using the Hopkins Symptom Checklist -90 Revised. Results: Compared to controls, the FHR-AFF sample was significantly impaired in auditory vigilance, while the FHR-SCZ sample was significantly worse in working memory. Both FHR groups showed significantly higher levels of physical anhedonia and some psychopathological dimensions than controls. Adjusting for physical anhedonia, phobic anxiety, depression, psychoticism, and obsessive-compulsive symptoms eliminated the FHR-AFF vigilance effects but not the working memory deficits in FHR-SCZ. Conclusions: The working memory deficit in FHR-SZ was the more robust of the cognitive impairments after accounting for psychopathological confounds and is supported as an endophenotype. Examination of larger samples of people at familial risk for different psychoses remains necessary to confirm these findings and to clarify the role of vigilance in FHR-AFF. (JINS, 2016, 22, 1026–1037)

Objectives: In a large cohort of boys with dystrophinopathies and their unaffected siblings, we examined whether consistently observed performance on digit span is due primarily to a verbal span or executive deficit. We additionally assessed whether digit span performance contributed to the observed variability in reading performance noted in this population. Methods: Performance of 170 boys with dystrophinopathy was compared to 95 unaffected sibling controls on measures of verbal function, reading, and digit span. Maximum digit span forward (DSF) and backward (DSB) lengths were converted to Z-scores using normative data. Independent sample t tests, analysis of variance, and hierarchical multiple regression were run (α=0.05). Results: Probands performed worse than controls on digit span, even after accounting for differences in general verbal function (p<.0001). Differences were significant for both DSF (p<.005) and DSB (p<.0001) span length, and an interaction effect yielded significantly worse DSB compared with DSF (p=.01). Reading performance was also lower in probands (p<.0001). The contribution of general level of verbal function, and forward and backward span lengths, did not vary between groups. Conclusions: In boys with dystrophinopathy, decreased performance on digit span appears to be due to both decreased span forward (measuring verbal span only) and backward (measuring verbal span and working memory). The extent to which sibling controls exhibited better performance compared to the probands was significantly greater for backward span when compared with forward span. Thus, immediate verbal memory and executive control are differentially compromised among boys with dystrophinopathy, and both of these abilities independently contribute to reading performance. (JINS, 2016, 22, 777–784)

Objectives: It is widely believed that phonemic fluency is more difficult than naming exemplars from a semantic category. Normative data in this regard are scarce, and there is considerable disagreement in the literature regarding the pattern in normal ageing and neurodegenerative conditions. Our objective was to provide normative data for semantic phonemic discrepancy scores from a large sample of older adults. Methods: A total of 5780 community-dwelling older adults were included in this prospective, longitudinal study. Discrepancy scores were calculated by subtracting phonemic fluency score from semantic fluency score for each participant. Quantile regression was used to estimate normative values stratified for age. Results: Subjects did better on testing of semantic fluency. The average discrepancy score was 9.18±6.89 words, (range, −20 to 37; n=5780). At the fiftieth percentile, those in their fifth decade produced 10 more “animals” than “letter F” words. Subjects scored one word less per decade, with an average of seven more “animal” words produced by those in their eighth decade. Conclusions: Our study is the first to provide normative data and confirms that, for animal versus letter F fluency, the semantic advantage persists into later life in a population-based sample of community-dwelling older adults. Given that a majority of clinical samples have confirmed a reverse of this pattern in Alzheimer’s dementia (i.e., loss of semantic advantage in Alzheimer’s disease, yielding a phonemic advantage), our findings support the clinical utility of brief fluency tests and encourage further research into their use in diagnosis and prediction of progression to dementia. (JINS, 2016, 22, 1–7)

Objectives: Patients with Parkinson’s disease often experience significant decline in verbal fluency over time; however, deep brain stimulation of the subthalamic nucleus (STN-DBS) is also associated with post-surgical declines in verbal fluency. The purpose of this study was to determine if Parkinson’s patients who have undergone bilateral STN-DBS have greater impairment in verbal fluency compared to Parkinson’s patients treated by medication only. Methods: A literature search yielded over 140 articles and 10 articles met inclusion criteria. A total of 439 patients with Parkinson’s disease who underwent bilateral STN-DBS and 392 non-surgical patients were included. Cohen’s d, a measure of effect size, was calculated using a random effects model to compare post-treatment verbal fluency in patients with Parkinson’s disease who underwent STN-DBS versus those in the non-surgical comparison group. Results: The random effects model demonstrated a medium effect size for letter fluency (d=−0.47) and a small effect size for category fluency (d=−0.31), indicating individuals with bilateral STN-DBS had significantly worse verbal fluency performance than the non-surgical comparison group. Conclusions: Individuals with Parkinson’s disease who have undergone bilateral STN-DBS experience greater deficits in letter and category verbal fluency compared to a non-surgical group. (JINS, 2016, 22, 478–485)

Objectives: Processing speed impairment is the most prevalent cognitive deficit in individuals with multiple sclerosis (MS). However, the neural mechanisms associated with processing speed remain under debate. The current investigation provides a dynamic representation of the functioning of the brain network involved in processing speed by examining effective connectivity pattern during a processing speed task in healthy adults and in MS individuals with and without processing speed impairment. Methods: Group assignment (processing speed impaired vs. intact) was based on participants’ performance on the Symbol Digit Modalities test (Parmenter, Testa, Schretlen, Weinstock-Guttman, & Benedict, 2010). First, brain regions involved in the processing speed task were determined in healthy participants. Time series from these functional regions of interest of each group of participants were then subjected to the effective connectivity analysis (Independent Multiple-Sample Greedy Equivalence Search and Linear, Non-Gaussian Orientation, Fixed Structure algorithms) that showed causal influences of one region on another during task performance. Results: The connectivity pattern of the processing speed impaired group was significantly different from the connectivity pattern of the processing speed intact group and of the healthy control group. Differences in the strength of common connections were also observed. Conclusions: Effective connectivity results reveal that MS individuals with processing speed impairment not only have connections that differ from healthy participants and MS individuals without processing speed impairment, but also have increased strengths of connections. (JINS, 2016, 22, 216–224)

Hispanics are the fastest growing ethnicity in the United States, yet there are limited well-validated neuropsychological tools in Spanish, and an even greater paucity of normative standards representing this population. The Spanish NIH Toolbox Cognition Battery (NIHTB-CB) is a novel neurocognitive screener; however, the original norms were developed combining Spanish- and English-versions of the battery. We developed normative standards for the Spanish NIHTB-CB, fully adjusting for demographic variables and based entirely on a Spanish-speaking sample. A total of 408 Spanish-speaking neurologically healthy adults (ages 18–85 years) and 496 children (ages 3–7 years) completed the NIH Toolbox norming project. We developed three types of scores: uncorrected based on the entire Spanish-speaking cohort, age-corrected, and fully demographically corrected (age, education, sex) scores for each of the seven NIHTB-CB tests and three composites (Fluid, Crystallized, Total Composites). Corrected scores were developed using polynomial regression models. Demographic factors demonstrated medium-to-large effects on uncorrected NIHTB-CB scores in a pattern that differed from that observed on the English NIHTB-CB. For example, in Spanish-speaking adults, education was more strongly associated with Fluid scores, but showed the strongest association with Crystallized scores among English-speaking adults. Demographic factors were no longer associated with fully corrected scores. The original norms were not successful in eliminating demographic effects, overestimating children’s performances, and underestimating adults’ performances on the Spanish NIHTB-CB. The disparate pattern of demographic associations on the Spanish versus English NIHTB-CB supports the need for distinct normative standards developed separately for each population. Fully adjusted scores presented here will aid in more accurately characterizing acquired brain dysfunction among U.S. Spanish-speakers. (JINS, 2016, 21, 364–374)

Objectives: Results from research conducted on the association between cannabis use and body mass index (BMI) reveal mixed findings. It is possible that individual differences in decision-making (DM) abilities may influence these associations. Methods: This study analyzed how amount of cannabis use, DM performance, and the interaction of these variables influenced BMI and clinical classifications of weight among adolescents (ages 14 to 18 years; 56% male; 77% Hispanic). The sample consisted primarily of cannabis users (n=238) without a history of significant developmental disorders, birth complications, neurological conditions, or history of mood, thought, or attention deficit/hyperactivity disorder at screening. Furthermore, few participants engaged frequently in other drug use (except for alcohol and nicotine). Results: Analyses revealed that more lifetime cannabis use was associated with a higher BMI and greater likelihood of being overweight/obese. Interactions between DM and cannabis use on BMI were not significant, and DM was not directly associated with BMI. Discussion: Our findings suggest that among adolescents, cannabis use is associated with a greater BMI regardless of DM abilities and this association is not accounted for by other potential factors, including depression, alcohol use, nicotine use, race, ethnicity, or IQ. (JINS, 2016, 22, 944–949)

Objectives Although primary dystonia is typically characterized as a movement disorder, it is also associated with cognitive alterations in the domain of executive functioning which may arise from changes in cortico-basal ganglia circuits. Specifically, in comparison to healthy controls, patients with dystonia show deficits in neuropsychological tests of cognitive flexibility. However, it is unclear whether cognitive inflexibility is caused by the pathomechanisms underlying primary dystonia or by confounding factors such as depression or symptom-related distraction.Methods The present study aimed to eliminate these confounds by examining cognitive flexibility in dystonia patients and in patients with similar motor symptoms but without a comparable central pathophysiology. Eighteen patients with primary blepharospasm, a common form of dystonia affecting the muscles around the eyes, and 19 patients with hemifacial spasm, a facial nerve disorder causing similar eyelid spasms, completed a computerized version of the Wisconsin Card Sorting Test (cWCST). The two groups were further compared on tests of global cognitive functioning, psychiatric symptoms, health status, and impulsiveness. Results Blepharospasm patients committed significantly more errors on the cWCST than patients with hemifacial spasm. Group differences were most pronounced with regard to integration errors, a measure of rule-inference processes on the cWCST. Integration errors were also associated with impulsiveness in patients with blepharospasm. Conclusions Primary blepharospasm is related to deficits in cognitive flexibility, even when blepharospasm patients are compared with patients who suffer from motor symptoms of non-dystonic origin. Our results support the possibility that cognitive inflexibility results from the specific pathophysiological processes underlying primary dystonia. (JINS, 2016, 22, 662–670)

It has recently been reported that individuals with multiple sclerosis (MS) are impaired on tasks requiring emotional processing and social cognition, including tasks of Theory of Mind (ToM) and facial affect recognition. The current pilot study examined the ability of individuals with MS to understand and interpret lies and sarcasm using a dynamic task: The Awareness of Social Inference Test (TASIT). Fifteen individuals with MS and 15 healthy controls (HCs) performed the Social Inference-Enriched subtest of the TASIT, in which they viewed video-taped social interactions in which lies and sarcasm are presented. Additionally, tests of cognition were also administered to better understand the relationship between specific cognitive abilities and the ability to understand lies and sarcasm. The MS group showed impairments in the ability to interpret and understand lies and sarcasm relative to HCs. These impairments were correlated with several cognitive abilities including processing speed, working memory, learning and memory, and premorbid IQ. The results indicate that the TASIT is a sensitive measure of social cognition in individuals with MS. Furthermore, performance on the TASIT was related to cognitive abilities. Results are discussed in terms of social cognition deficits in MS and how they relate to cognitive abilities. (JINS, 2016, 22, 83–88)

Objectives: The aim of this study was to demonstrate the utility of an evidence-based assessment (EBA) model to establish a multimodal set of tools for identifying students at risk for perceived post-injury academic problems. Methods: Participants included 142 students diagnosed with concussion (age: M=14.95; SD=1.80; 59% male), evaluated within 4 weeks of injury (median=16 days). Demographics, pre-injury history, self- and parent-report measures assessing symptom severity and executive functions, and cognitive test performance were examined as predictors of self-reported post-injury academic problems. Results: Latent class analysis categorized participants into “high” (44%) and “low” (56%) levels of self-reported academic problems. Receiver operating characteristic analyses revealed significant discriminative validity for self- and parent-reported symptom severity and executive dysfunction and self-reported exertional response for identifying students reporting low versus high academic problems. Parent-reported symptom ratings [area under the receiver operating characteristic curve (AUC)=.79] and executive dysfunction (AUC=.74), and self-reported ratings of executive dysfunction (AUC=.84), symptoms (AUC=.80), and exertional response (AUC=.70) each classified students significantly better than chance (ps<.001). Hierarchical logistic regression indicated that, of the above, self-reported symptoms and executive dysfunction accounted for the most variance in the prediction of self-reported academic problems. Conclusions: Post-concussion symptom severity and executive dysfunction significantly predict perceived post-injury academic problems. EBA modeling identified the strongest set of predictors of academic challenges, offering an important perspective in the management of concussion by applying traditional strengths of neuropsychological assessment to clinical decision making. (JINS, 2016, 22, 1038–1049)

Objectives: The Paced Auditory Serial Addition Test (PASAT) is used to assess cognitive status in multiple sclerosis (MS). Although the mathematical demands of the PASAT seem minor (single-digit arithmetic), cognitive psychology research links greater mathematical ability (e.g., algebra, calculus) to more rapid retrieval of single-digit math facts (e.g., 5+6=11). The present study evaluated the hypotheses that (a) mathematical ability is related to PASAT performance and (b) both the relationship between intelligence and PASAT performance as well as the relationship between education and PASAT performance are both mediated by mathematical ability. Methods: Forty-five MS patients were assessed using the Wechsler Test of Adult Reading, PASAT and Calculation Subtest of the Woodcock-Johnson-III. Regression based path analysis and bootstrapping were used to compute 95% confidence intervals and test for mediation. Results: Mathematical ability (a) was related to PASAT (β=.61; p<.001) and (b) fully mediated the relationship between Intelligence and PASAT (β=.76; 95% confidence interval (CI95)=.28, 1.45; direct effect of Intelligence, β=.42; CI95=−.39, 1.23) as well as the relationship between Education and PASAT (β=2.43, CI95=.81, 5.16, direct effect of Education, β=.83, CI95=−1.95, 3.61). Discussion: Mathematical ability represents a source of error in the clinical interpretation of cognitive decline using the PASAT. Domain-specific cognitive reserve is discussed. (JINS, 2016, 22, 375–378)

Objectives: Several studies have found impaired response inhibition, measured by a stop-signal task (SST), in individuals who are currently symptomatic for obsessive-compulsive disorder (OCD). The aim of this study was to assess stop-signal reaction time (SSRT) performance in individuals with a lifetime diagnosis of OCD, in comparison to a healthy control group. This is the first study that has examined OCD in participants along a continuum of OCD severity, including approximately half of whom had sub-syndromal symptoms at the time of assessment. Methods: OCD participants were recruited primarily from within the OCD clinic at a psychiatric hospital, as well as from the community. Healthy controls were recruited from the community. We used the stop signal task to examine the difference between 21 OCD participants (mean age, 42.95 years) and 40 healthy controls (mean age, 35.13 years). We also investigated the relationship between SST and measures of OCD, depression, and anxiety severity. Results: OCD participants were significantly slower than healthy controls with regard to mean SSRT. Contrary to our prediction, there was no correlation between SSRT and current levels of OCD, anxiety, and depression severity. Conclusions: Results support prior studies showing impaired response inhibition in OCD, and extend the findings to a sample of patients with lifetime OCD who were not all currently above threshold for diagnosis. These findings indicate that response inhibition deficits may be a biomarker of OCD, regardless of current severity levels. (JINS, 2016, 22, 785–789)

Objectives Growing evidence demonstrates that (a) executive functioning (EF) becomes deleteriously affected by engagement in the emotion regulation strategy known as expressive suppression and (b) EF shows considerable functional and neuroanatomical overlap with motor output. The current study aimed to bridge these two literatures by examining the relationships between naturally occurring expressive suppression and several different aspects of motor output, including action planning, action learning, and motor-control speed and accuracy. In addition, we investigated whether any identified relationships could be explained by EF. Methods Fifty-one healthy young adults completed selected subtests from the Delis-Kaplan Executive Function System as indices of EF, a self-report measure of expressive suppression, and a computerized motor sequencing task (Push Turn Taptap task; PTT) designed to assess action planning, action learning, and motor control speed and accuracy. Results Hierarchical regressions using each aspect of PTT performance as the dependent variable revealed that higher than usual self-reported expressive suppression on the day of testing (relative to the 2 weeks preceding testing) was associated with longer action-planning latencies. This relationship was fully explained by EF. No other PTT variables related to expressive suppression on the day of testing. Conclusions These results suggest that increased expressive suppression in daily life is associated with slower action planning, an aspect of motor output that is reliant on EF, highlighting the importance of factors that lead to intra-individual fluctuations in EF and motor performance. (JINS, 2016, 22, 671–681)

Objectives: The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome. Methods: Thirty-six patients with ADS (mean age=12.2 years, SD=2.7, range: 7–16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls. Results: Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5 SD below normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed among 6/32 patients, but this did not differ significantly from controls. Twelve of 36 patients received a diagnosis of MS within 3 years post-ADS. Patients with MS did not differ from children with monophasic ADS in terms of cognitive performance at the 6-months follow-up. Fatigue symptoms were reported in 50% of patients, irrespective of MS diagnosis. Presence of brain lesions at onset and 6 months post-incident demyelinating event did not associate with cognitive outcome. Conclusions: Children with ADS experience a favorable short-term neurocognitive outcome, even those confirmed to have MS. Longitudinal evaluations of children with monophasic ADS and MS are required to determine the possibility of late-emerging sequelae and their time course. (JINS, 2016, 22, 1050–1060)

Objectives: There is a well-known association between memory impairment and major depressive disorder (MDD). Additionally, recent studies are also showing resting-state functional magnetic resonance imaging (rsMRI) abnormalities in active and remitted MDD. However, no studies to date have examined both rs connectivity and memory performance in early course remitted MDD, nor the relationship between connectivity and semantically cued episodic memory. Methods: The rsMRI data from two 3.0 Tesla GE scanners were collected from 34 unmedicated young adults with remitted MDD (rMDD) and 23 healthy controls (HCs) between 18 and 23 years of age using bilateral seeds in the hippocampus. Participants also completed a semantically cued list-learning test, and their performance was correlated with hippocampal seed-based rsMRI. Regression models were also used to predict connectivity patterns from memory performance. Results: After correcting for sex, rMDD subjects performed worse than HCs on the total number of words recalled and recognized. rMDD demonstrated significant in-network hypoactivation between the hippocampus and multiple fronto-temporal regions, and multiple extra-network hyperconnectivities between the hippocampus and fronto-parietal regions when compared to HCs. Memory performance negatively predicted connectivity in HCs and positively predicted connectivity in rMDD. Conclusions Even when individuals with a history of MDD are no longer displaying active depressive symptoms, they continue to demonstrate worse memory performance, disruptions in hippocampal connectivity, and a differential relationship between episodic memory and hippocampal connectivity. (JINS, 2016, 22, 225–239)

Objectives: This research retrospectively analyzed the effect of education on cognitive interventions carried out in patients with mild Alzheimer’s disease (AD). Methods: The total sample consisted of 75 patients with mild AD receiving treatment with cholinesterase inhibitors. The participants were divided into two groups: cognitive intervention (IG; n=45) and waiting list (WLG; n=30). Patients in the IG received either the Big Brain Academy (n=15) or the Integrated Psychostimulation Program (n=30) during 12 weeks. The influence of education on intervention effect was analyzed comparing mean change scores of the two study groups in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), stratified by educational level. The potential effect of age, sex, cognitive status, and type of intervention was examined using post hoc stratification analyses. Results: Higher education was associated with faster cognitive decline in the WLG (effect size=0.51; p<.01). However, cognitive evolution was not influenced by education in the IG (effect size=0.12; p=.42). Conclusions: Our results suggest that cognitive intervention might delay accelerated cognitive decline in higher educated individuals with mild AD. (JINS, 2016, 23, 1–6)