Objectives: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. Methods: Here, we used longitudinal cognitive data from 1256 late–middle aged adults from the Wisconsin Registry for Alzheimer’s Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. Results: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40–70 years). Conclusions: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119–133)

Objectives: The high rate of cannabis (CAN) use in emerging adults is concerning given prior research suggesting neurocognitive deficits associated with CAN use in youth. Regular CAN use downregulates endocannabinoid activity, while aerobic exercise upregulates cannabinoid receptor 1 activity and releases endocannabinoids. Here we investigate the influence of regular CAN use on neuropsychological performance, and whether aerobic fitness moderates these effects. Methods: Seventy-nine young adults (37 CAN users) aged 16–26 participated. Groups were balanced for aerobic fitness level. Exclusion criteria included: left-handedness, past-year independent Axis-I disorders, major medical/neurologic disorders, prenatal issues, or prenatal alcohol/illicit drug exposure. After 3 weeks of abstinence, participants completed a neuropsychological battery and a maximal oxygen consumption test (VO2 max). Multiple regressions tested whether past-year CAN use, VO2 max, and CAN*VO2 max interaction predicted neuropsychological performance, controlling for past-year alcohol use, cotinine, gender, and depression symptoms. Results: Increased CAN use was associated with decreased performance on working memory and psychomotor tasks. High aerobic fitness level was related to better performance on visual memory, verbal fluency, and sequencing ability. CAN*VO2 max predicted performance of psychomotor speed, visual memory, and sequencing ability. Conclusions: Following monitored abstinence, increased CAN use was associated with poorer performance in working memory and psychomotor speed. Higher aerobic fitness level moderated the impact of CAN on visual memory, executive function and psychomotor speed, as more aerobically fit CAN users demonstrated better performance relative to low-fit users. Therefore, aerobic fitness may present an affordable and efficacious method to improve cognitive functioning in CAN users. (JINS, 2019, 25, 134–145)

Objectives: The aim of this study was to investigate executive skills in children with dystrophinopathy and to examine the association between executive functions and dystrophin gene mutation position. Methods: Fifty boys with dystrophinopathy (mean age, 11 years 0 months; ages range, 5 to 17 years) completed measures of intellectual functioning (IF), working memory and executive functioning [including Digit Span (working memory) and measures from the NIH Toolbox (selective attention/inhibitory control, set shifting, working memory, and processing speed)]. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Mutation positions were categorized into three groups (upstream exon 30, 31–62, and downstream exon 63). Paired-samples t tests compared performance on executive measures to IF, and a one-way (three-group) multivariate analysis of covariance compared cognitive performance with mutation location controlling for motor functioning. Results: Mean performance on all executive measures was significantly lower than IF. Parents were also more likely to rate their child with dystrophinopathy as having clinically significant executive difficulties on the Shift, Emotional Control, and Behavior Regulation indices of the BRIEF. Mutation analyses resulted in small groups limiting power to detect subtle differences. Those with a downstream mutation position had significantly poorer performance on IF and Total Digit Span, but not on other measures of executive function including behavior. Conclusions: Individuals with dystrophinopathy have executive skill deficits, but they are not generally associated with more distal mutations. (JINS, 2019, 25, 146–155)

Objectives: Essential tremor (ET) is a movement disorder characterized by action tremor which impacts motor execution. Given the disrupted cerebellar-thalamo-cortical networks in ET, we hypothesized that ET could interfere with the control mechanisms involved in regulating motor performance. The ability to inhibit or stop actions is critical for navigating many daily life situations such as driving or social interactions. The current study investigated the speed of action initiation and two forms of action control, response stopping and proactive slowing in ET. Methods: Thirty-three ET patients and 25 healthy controls (HCs) completed a choice reaction task and a stop-signal task, and measures of going speed, proactive slowing and stop latencies were assessed. Results: Going speed was significantly slower in ET patients (649 ms) compared to HCs (526 ms; F(1,56) = 42.37; p <.001; η2 = .43), whereas proactive slowing did not differ between groups. ET patients exhibited slower stop signal reaction times (320 ms) compared to HCs (258 ms, F(1,56) = 15.3; p <.00; η2 = .22) and more severe motor symptoms of ET were associated with longer stopping latencies in a subset of patients (Spearman rho = .48; p <.05). Conclusions: In line with previous studies, ET patients showed slower action initiation. Additionally, inhibitory control was impaired whereas proactive slowing remained intact relative to HCs. More severe motor symptoms of ET were associated with slower stopping speed, and may reflect more progressive changes to the cerebellar-thalamo-cortical network. Future imaging studies should specify which structural and functional changes in ET can explain changes in inhibitory action control. (JINS, 2019, 25, 156–164)

Objectives: The aim of our study was to assess the differences in facial emotional recognition (FER) between patients with first-episode psychosis (FEP), patients with multi-episode schizophrenia (SCH), and healthy controls (HC) and to find possible correlations of FER with psychopathology in the two patient groups. Methods: We performed a cross-sectional study enrolling 160 patients from two psychiatric hospitals in Croatia (80 FEP and 80 SCH) and 80 HC during the period from October 2015 until October 2017. Patients were assessed once during their hospital treatment, using the Penn Emotion Recognition Task for assessment of FER, rating scales for psychopathology and depression and self-reporting questionnaires for impulsiveness, aggression, and quality of life. Results: The number of correctly identified emotions significantly decreased from HC to FEP [Δ −7%; 95% confidence interval (CI) [−12% to −3%], effect size r = 0.30] and more markedly in SCH (Δ −15%; 95% CI [−25% to −10%], effect size r = 0.59) after the adjustment for age and gender and correction for multiple testing. Correct FER for negative emotions, but not for happiness and neutral emotions, had a statistically significant negative correlation with some features on the scales of psychopathology, impulsivity and aggression in both patient groups. Conclusions: Impairment of FER is present from the first episode of schizophrenia and increases further with multiple psychotic episodes, but it may depend on or contribute to clinical symptoms. Therefore, assessment of FER should be included in the clinical assessment and integrated in the plan of treatment from the beginning of the illness. (JINS, 2019, 25, 165–173)

Objectives: Antisaccade error rate has been proposed to be one of the most promising endophenotypes for schizophrenia. Increased error rate in patients has been associated with working memory, attention and other executive function impairments. The relationship between antisaccade error rate and other neuropsychological processes in patients compared to healthy controls has not been explored in depth. This study aimed to replicate the finding of heightened antisaccade error rate in patients and determine which cognitive processes were most strongly associated with antisaccade error rate in both patients and controls. In addition, the study investigated whether different antisaccade task paradigms engage different cognitive processes. Methods: One hundred and ninety-one participants (54 patients with schizophrenia/schizoaffective disorder and 137 controls) completed the antisaccade task, which included both gap and step task parameters. Neuropsychological measures were obtained using the MCCB and the Stroop task. Results: The current study replicated a pronounced antisaccade error rate deficit in patients. In patients, working memory variance was most significantly associated with antisaccade errors made during the step condition, while attentional processes were most associated with errors made during the gap condition. In controls, overall global cognitive performance was most associated with antisaccade rates for both gap and step conditions. Conclusions: The current study demonstrates that in schizophrenia patients, but not controls, elevated antisaccade error rate is associated with attention and working memory, but not with global cognitive impairment or psychopathological processes. Our novel findings demonstrate that the gap and step conditions of the antisaccade task engage different cognitive processes. (JINS, 2019, 25, 174–183)

Objectives: The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e., preclinical) versus 32 demographically-matched familial non-carriers (n = 44). Studying preclinical carriers offers a rare glimpse into emergent disease, environmentally and genetically contextualized through comparison to familial controls. Methods: Evaluating personnel blinded to carrier status administered a standardized neuropsychological battery assessing attention, speed, executive function, language, memory, spatial ability, and social cognition. Results from mixed effect modeling were corrected for multiplicity of comparison by the false discovery rate method, and results were considered significant at p < .05. To control for potential interfamilial variation arising from enrollment of six families, family was treated as a random effect, while carrier status, age, gender, and education were treated as fixed effects. Results: Group differences were detected in 17 of 31 cognitive scores and spanned all domains except spatial ability. As hypothesized, carriers performed worse on specific measures of executive function, and social cognition, but also on measures of attention, speed, semantic processing, and memory storage and retrieval. Conclusions: Most notably, group differences arose on measures of memory storage, challenging long-standing ideas about the absence of amnestic features on neuropsychological testing in early bvFTD. Current findings provide important and clinically relevant information about specific measures that may be sensitive to early bvFTD, and advance understanding of neurocognitive changes that occur early in the disease. (JINS, 2019, 25, 184–194)

Objectives: The aim of this study was to assess the psychometric properties of a Swedish version of the Hayling test (HT-S) and its clinical utility in a group of patients with different frontotemporal dementia (FTD) syndromes. Early diagnosis of FTD is a challenge and requires a broad arsenal of assessment methods, neuropsychological tests not the least. The Hayling test assesses executive functions including initiation, efficiency and response inhibition. Methods: Seventy-six healthy controls were included as well as patients with the behavioral variant FTD (bvFTD; n = 17), semantic dementia (SD, n = 6), and progressive supranuclear palsy (n = 12). The Color Word Interference Test was administered to examine the construct validity. Results: Age showed a correlation with better performances in younger participants whereas the importance of sex and education were less evident. The split half reliability and internal consistency were equal to, or better, than reported for the original version. The interrater reliability was excellent. The construct validity was supported, nevertheless indicating partly different processes behind the performances of the two tests. The FTD group performed significantly worse than healthy controls on efficiency and response inhibition and there were also significant differences in performances between the syndromes despite small samples. Conclusions: The psychometric properties and clinical utility of the Swedish version are satisfactory for measuring efficiency and response inhibition with results indicating dissimilar profiles in the performances in the different syndromes. These results need to be corroborated in larger samples. (JINS, 2019, 25, 195–203)

Objectives: To adequately monitor the course of cognitive functioning in persons with moderate to severe dementia, relevant cognitive tests for the advanced dementia stages are needed. We examined the ability of a test developed for the advanced dementia stages, the Severe Impairment Battery Short version (SIB-S), to measure cognitive change over time. Second, we examined type of memory impairment measured with the SIB-S in different dementia stages. Methods: Participants were institutionalized persons with moderate to severe dementia (N = 217). The SIB-S was administered at 6-month intervals during a 2-year period. Dementia severity at baseline was classified according to Global Deterioration Scale criteria. We used mixed models to evaluate the course of SIB-S total and domain scores, and whether dementia stage at baseline affected these courses. Results: SIB-S total scores declined significantly over time, and the course of decline differed significantly between dementia stages at baseline. Persons with moderately severe dementia declined faster in mean SIB-S total scores than persons with moderate or severe dementia. Between persons with moderate and moderately severe dementia, there was only a difference in the rate of decline of semantic items, but not episodic and non-semantic items. Conclusions: Although modest floor and slight ceiling effects were noted in severe and milder cases, respectively, the SIB-S proved to be one of few available adequate measures of cognitive change in institutionalized persons with moderate to severe dementia. (JINS, 2019, 25, 204–214)

Objectives: Type 2 diabetes mellitus has been linked with cognitive decrement and an increased risk of dementia in older people. Less is known about whether diabetes affects cognition at younger ages. The objective of this meta-analysis was to examine possible differences (effect sizes) in cognitive performance between middle-aged type 2 diabetic patients and healthy controls. Secondary aim was to examine whether age is related to the magnitude of effect sizes. Methods: Electronic databases and lists of references of selected articles were used to search for studies examining type 2 diabetes and cognition in patients under age 65 compared to healthy controls. Twelve studies met the inclusion criteria. Standardized mean differences (Hedges’s g) were calculated for main cognitive domains and their subdomains. Association between age and effect sizes was evaluated with meta-regression analyses. Publication bias and methodological quality of the studies were assessed. Results: Patients performed worse than controls in several cognitive functions. The largest differences were found in information processing speed (g = −0.68), attention/concentration (g = −0.55), executive functions (g = −0.51), and working memory (g = −0.51). There was no significance difference in visual memory (g = −0.15). Age was significantly related to the effect size in information processing speed, language, verbal memory and visual memory. However, the direction of association varied across these cognitive domains. Conclusions: The results suggest that cognitive decrement in diabetes is not restricted to older people, but may begin to appear in middle age. More attention should be paid to early recognition and treatment of diabetes-related cognitive decrement in healthcare systems. (JINS, 2019, 25, 215–229)

Objectives: Reading aloud (vocal production) enhances memory relative to reading silently, the Production Effect (PE) in memory. Thus, vocalization has been suggested as a mnemonic device. The current study tested the PE in a sample of adults with ADHD and in a control sample, evaluating verbal learning. Methods: Twenty adults with ADHD and 21 controls learned a list of words, half by reading aloud and half by reading silently. Free recall test followed. The participants with ADHD performed the task twice (in two different sessions in a counterbalanced order), before self-administration of a single dose of methylphenidate (MPH) and 60-min after dosage. Results: PEs were found for all groups. Memory was better for the controls than for the ADHD group (with or without MPH). In the ADHD group, recall rates and the PE were higher with than without MPH. Conclusions: These results suggest that vocalization yields a larger memory gain with MPH. Possibly, MPH enables the ADHD participants to better shift their attention to the aloud words, enhancing their retrieval rates. Theoretically, these findings stress the role of attention in the PE. (JINS, 2019, 25, 230–235)