The purpose of the current study was to determine if self-reported lifetime marijuana use moderates the relationship between interleukin-6 (IL-6) and neurocognitive performance. Participants included 161 African American adults (50.3% women), with a mean age of 45.24 (SD=11.34). Serum was drawn upon entry into the study and participants completed a demographic questionnaire, which included drug use history, and a battery of neuropsychological tests. Using multiple regression analyses and adjusting for demographic covariates, the interaction term comprised of IL-6 and self-reported lifetime marijuana use was significantly associated with poorer performance on the Written (β=−.116; SE=.059; p=.049) and Oral trials (β=−.143; SE=.062; p=.022) of the Symbol Digit Modalities Test, as well as the Trail Making Test trial A (β=.157; SE=.071; p=.028). Current findings support previous literature, which presents the inverse relationship between IL-6 and neurocognitive dysfunction. The potential protective properties of marijuana use in African Americans, who are at increased risk for inflammatory diseases, are discussed. (JINS, 2014, 20, 773–783)

To assess recovery of cognitive effects, we investigated neuropsychological performance after 1 month of monitored abstinence in teens with histories of heavy episodic drinking, protracted marijuana use, or concomitant use of alcohol and marijuana. Adolescents (ages 16–18 years) with histories of heavy episodic drinking (HED; n=24), marijuana use (MJ; n=20), both heavy alcohol and marijuana use (HED+MJ; n=29), and socio-demographically similar control teens (CON; n=55) completed a neuropsychological battery following 4 weeks of monitored abstinence. Groups were similar on 5th grade standardized test scores, suggesting comparable academic functioning before onset of substance use. Relative to CON, HED showed poorer cognitive flexibility (p=.006), verbal recall (p=.024), semantic clustering (p=.011), and reading skills (p=.018). MJ performed worse than CON on inhibition task accuracy (p=.015), cued verbal memory (p=.031), and psychomotor speed (p=.027). Similar to HED youth, HED+MJ showed differences relative to CON on cognitive flexibility (p=.024) and verbal recall (p=.049). As with MJ teens, HED+MJ showed poorer task accuracy (p=.020). Unique to the HED+MJ group was poorer working memory (p=.012) relative to CON. For all substance using participants, worse performance across domains correlated with more lifetime use of alcohol and of marijuana, more withdrawal symptoms from alcohol, and earlier age of onset of marijuana use (ps<.05). Heavy alcohol use, marijuana use, and concomitant use of both substances during adolescence appear to be associated with decrements in cognitive functioning, and each substance (or combination of substances) may be linked to poorer performance in specific cognitive domains (JINS, 2014, 20, 784–795).

Cognitive impairment is often reported in pediatric-onset multiple sclerosis (MS). Using serial cognitive data from 35 individuals with pediatric-onset MS, this study examined how age at disease-onset and proxies of cognitive reserve may impact cognitive maturation over the course of childhood and adolescence. Neuropsychological evaluations were conducted at baseline and up to four more assessments. Of the 35 participants, 7 completed only one assessment, 5 completed two assessments, 13 completed three assessments, 10 completed four or more assessments. Growth curve modeling was used to assess longitudinal trajectories on the Trail Making Test-Part B (TMT-B) and the Symbol Digit Modalities (SDMT; oral version) and to examine how age at disease onset, baseline Full Scale IQ, and social status may moderate rate of change on these measures. Mean number of evaluations completed per patient was 2.8. Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p=.001) and SDMT (p=.005). Baseline IQ and parental social status did not moderate any of the cognitive trajectories. Findings suggest that younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory. Proxies of cognitive reserve did not protect against the progression of decline on these measures. Young patients with MS should be advised to seek follow-up cognitive evaluation to assess cognitive maturation and to screen for the potential late emergence of cognitive deficits. (JINS, 2014, 20, 1–9)

Recent reports suggest that cognition is relatively preserved in some schizophrenia patients. However, little is known about the functional advantage these patients may demonstrate. The purpose of this study was to identify cognitively normal patients with a recently developed test battery and to determine the functional benefit of this normality relative to cognitively impaired patients. Average-range cognitive ability was defined by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) composite score (T≥40) and applied to 100 patients with schizophrenia or schizoaffective disorder and to 81 non-psychiatric research participants. With group assignment adjusted for demographic variables, this procedure yielded 14 cognitively normal patients, 21 cognitively impaired patients, and 21 healthy adults with normal-range MCCB scores. Cognitively normal patients were indistinguishable from controls across all MCCB scales. Furthermore, their performance was superior to impaired patients on all scales except Social Cognition. Cognitively normal patients were also superior to impaired patients on a summary index of simulated life skills and functional competence. Nevertheless, both patient groups were equally disadvantaged relative to controls in independent community living. These findings suggest that normal-range cognition exists in schizophrenia, but fails to translate into enhanced community outcome. (JINS, 2014, 20, 1–7)

Prior research using performance-based assessment of functional impairment has informed a novel neuropsychological model of everyday action impairment in dementia in which omission errors (i.e., failure to complete task steps) dissociate from commission errors (i.e., inaccurate performance of task steps) and have unique neuropsychological correlates. However, this model has not been tested in other populations. The present study examined whether this model extends to schizophrenia. Fifty-four individuals with schizophrenia or schizoaffective disorder were administered a neuropsychological protocol and the Naturalistic Action Test (NAT), a performance-based measure of everyday action. A principal component analysis (PCA) was performed to examine the construct(s) comprising everyday action impairment, and correlations between the resultant component(s) and neuropsychological tests were examined. Results showed that omissions and a subset of commissions were distinct components of everyday action. However, results did not support unique associations between these components and specific neuropsychological measures. These findings extend the omission-commission model to schizophrenia and may have important implications for efficient assessment and effective rehabilitation of functional impairment, such as the potential efficacy of targeted interventions for the rehabilitation of omission and commission deficits in everyday functioning. Larger studies with prospective designs are needed to replicate the present preliminary findings. (JINS, 2014, 20, 1–10)

Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17–86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity. (JINS, 2014, 20, 1–14)

Subjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI cohort to determine whether they are a valuable inclusion in the diagnosis of MCI or, alternatively, if they contribute to misdiagnosis. Subgroups of MCI were derived using cluster analysis of baseline neuropsychological test data from 448 ADNI MCI participants. Cognitive complaints were assessed via the Everyday Cognition (ECog) questionnaire, and discrepancy scores were calculated between self- and informant-report. Cluster analysis revealed Amnestic and Mixed cognitive phenotypes as well as a third Cluster-Derived Normal subgroup (41.3%), whose neuropsychological and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarker profiles did not differ from a “robust” normal control group. This cognitively intact phenotype of MCI participants overestimated their cognitive problems relative to their informant, whereas Amnestic MCI participants with objective memory impairment underestimated their cognitive problems. Underestimation of cognitive problems was associated with positive CSF AD biomarkers and progression to dementia. Overall, there was no relationship between self-reported cognitive complaints and objective cognitive functioning, but significant correlations were observed with depressive symptoms. The inclusion of self-reported complaints in MCI diagnostic criteria may cloud rather than clarify diagnosis and result in high rates of misclassification of MCI. Discrepancies between self- and informant-report demonstrate that overestimation of cognitive problems is characteristic of normal aging while underestimation may reflect greater risk for cognitive decline. (JINS, 2014, 20, 1–12)

The purpose was to compare the Spanish language picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR) and the Mini Mental State Exam (MMSE) in identifying very mild dementia among Spanish speaking Latino patients. The tests and an independent diagnostic assessment were administered to 112 Latino patients free of medically diagnosed dementia from an urban primary care clinic. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to examine differences in the operating characteristics of the pFCSRT+IR and the MMSE. Cut scores were manipulated to equate sensitivities (specificities) at clinically relevant values to compare differences in specificities (sensitivities) using the Pearson Chi Square test. Youden’s index was used to select the optimal cut scores. Twenty-four of the 112 primary care patients (21%) received a research dementia diagnosis, indicating a substantial burden of unrecognized dementia. MMSE scores but not free recall scores were associated with years of education in patients free of dementia. AUC was significantly higher for free recall than for MMSE. Free recall performed significantly better than the MMSE in sensitivity and in specificity. Using optimal cut scores, patients with impaired free recall were 10 times more likely to have dementia than patients with intact recall, and patients with impaired MMSE scores were 4.5 times more likely to have dementia than patients with intact scores. These results suggest that the Spanish language pFCSRT+IR may be an effective tool for dementia screening in educationally diverse Latino primary care populations. (JINS, 2014, 20, 1–8)

In 2006, the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards recommended a 5-Minute Protocol as a brief screening instrument for vascular cognitive impairment (VCI). We report demographically adjusted norms for the 5-Minute Protocol and its relation to other measures of cognitive function and cerebrovascular risk factors. We performed a cross-sectional analysis of 7199 stroke-free adults in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study on the NINDS-CSN 5-Minute Protocol score. Total scores on the 5-Minute Protocol were inversely correlated with age and positively correlated with years of education, and performance on the Six-Item Screener, Word List Learning, and Animal Fluency (all p-values <.001). Higher cerebrovascular risk on the Framingham Stroke Risk Profile (FSRP) was associated with lower total 5-Minute Protocol scores (p <.001). The 5-Minute Protocol also differentiated between participants with and without confirmed stroke and with and without stroke symptom histories (p <.001). The NINDS-CSN 5-Minute Protocol is a brief, easily administered screening measure that is sensitive to cerebrovascular risk and offers a valid method of screening for cognitive impairment in populations at risk for VCI. (JINS, 2014, 20, 1–12)

Some individuals with multiple sclerosis (MS) show decrements in long-term memory (LTM) while other individuals do not. The theory of cognitive reserve suggests that individuals with greater pre-morbid intellectual enrichment are protected from disease-related cognitive decline. How intellectual enrichment affords this benefit remains poorly understood. The present study tested an exploratory meditational hypothesis whereby working memory (WM) capacity may mediate the relationship between intellectual enrichment and verbal LTM decline in MS. Intellectual enrichment, verbal LTM, and WM capacity were estimated with the Wechsler Test of Adult Reading and Peabody Picture Vocabulary Test, delayed recall of the Hopkins Verbal Learning Test-Revised and Logical Memory of the Wechsler Memory Scale, and Digit Span Total, respectively. Intellectual enrichment predicted LTM (B=.54; p=.003) and predicted WM capacity (B=.91; p<.001). WM capacity predicted LTM, (B=.44; p<.001) and fully mediated the relationship between intellectual enrichment (B=.24; p=.27) and LTM (B=.33, p=.03), Sobel test, Z=3.31, p<.001. These findings implicate WM capacity as an underlying mechanism of cognitive reserve and are an initial first step in understanding the relationship between intellectual enrichment, WM, and LTM in MS. (JINS, 2014, 20, 1–5)