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OBJECTIVES: To determine associations among DNA methylation of brain-derived neurotrophic factor (BDNF) and RAS p21 protein activator 2 (RASA2) genes with processing speed and perceived cognitive function. SAMPLE & SETTING: This was a cross-sectional, secondary analysis of baseline data from a randomized controlled trial, the Exercise Program in Cancer and Cognition Study. METHODS & VARIABLES: Data included M values for DNA methylation of the BDNF and RASA2 genes; processing speed, objectively measured using the Grooved Pegboard and Digit Vigilance Test scores; and perceived cognitive function, self-reported using the Patient Assessment of Own Functioning Inventory. Regression analysis was conducted. RESULTS: Greater methylation of cg21291635 of the BDNF gene (p = 0.01) and cg20247102 of the RASA2 gene (p = 0.013) were associated with poorer processing speed, whereas greater methylation of cg20108357 of the BDNF gene (p < 0.001) and cg00567892 of the RASA2 gene (p = 0.019) were associated with better perceived cognitive function. IMPLICATIONS FOR NURSING: Gene methylation variations were demonstrated, suggesting the genes' potential roles and two possible distinct mechanisms of cognitive function in cancer. [ABSTRACT FROM AUTHOR]

Introduction: Neighborhood socioeconomic status (NSES) has been linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic whites (NHWs) and Mexican Americans (MAs) from the Health and Aging Brain: Health Disparities Study (HABS-HD). Methods: The HABS-HD is a longitudinal study conducted at the University of North Texas Health Science Center. The final sample analyzed (n = 1,312) were 50 years or older, with unimpaired cognition, and underwent an interview, neuropsychological examination, imaging, and blood draw. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered socioeconomic variables. Executive function and processing speed were assessed by the trail making tests (A and B) and the digit-symbol substitution test, respectively. Linear regression was used to assess the association of ADI and cognitive measures. Results: MAs were younger, more likely to be female, less educated, had higher ADI scores, performed worse on trails B (all p < 0.05), and had lower prevalence of APOE4 + when compared to NHWs (p < 0.0001). A higher percentage of MAs lived in the most deprived neighborhoods than NHWs. For NHWs, ADI did not predict trails B or DSS scores, after adjusting for demographic variables and APOE4. For MAs, ADI predicted trails A, trails B, and DSS after adjusting for demographic covariates and APOE4 status. Conclusion: Our study revealed that living in an area of higher deprivation was associated with lower cognitive function in MAs but not in NHWs, which is important to consider in future interventions to slow cognitive decline. [ABSTRACT FROM AUTHOR]

Individuals' reaction time (RT) slopes in tasks of mental rotation have been found to be related to other measures of visual-spatial abilities, and thus are often viewed as a psychometric measure of visual-spatial abilities. The common interpretation of individual RT slopes is as a measure of the speed at which the rotation is carried out. However, electroencephalography studies have found that the process of mental rotation continues after response selection has been carried out, casting doubt on the interpretation of RT slopes as measures of the speed of mental rotation. This study made use of electroencephalography techniques to directly capture individual differences in the speed of mental rotation and assess their association with visual-spatial abilities. We found that individual differences in mental rotation speed are not related to individual differences in RT slopes. Moreover, a computation model supports an alternative explanation by which RT slopes reflect individual differences in differential tolerances for stimulus identification within mental rotation tasks. Public Significance Statement: This research challenges the long-held assumption that reaction time slopes in mental rotation tasks directly reflect individual differences in visual-spatial processing speed. Instead, by employing electroencephalography and behavioral computation models, our findings suggest that these reaction time slopes reflect individual differences in decision thresholds. These findings have significant implications for understanding individual variations in mental rotation performance and spatial reasoning skills. [ABSTRACT FROM AUTHOR]

IntroductionCardiovascular fat is a novel risk factor that may link to dementia. Fat volume and radiodensity are measurements of fat quantity and quality, respectively. Importantly, high fat radiodensity could indicate healthy or adverse metabolic processes.MethodsThe associations of cardiovascular fat (including epicardial, paracardial, and thoracic perivascular adipose tissue [PVAT]) quantity and quality assessed at mean age of 51 with subsequent cognitive performance measured repeatedly over 16 years of follow-up were examined using mixed models among 531 women.ResultsHigher thoracic PVAT volume was associated with a higher future episodic memory (β[standard error (SE)] = 0.08 [0.04], P = 0.033), while higher thoracic PVAT radiodensity with lower future episodic (β[SE] = -0.06 [0.03], P = 0.045) and working (β[SE] = -0.24 [0.08], P = 0.003) memories. The latter association is prominent at higher volume of thoracic PVAT.DiscussionMid-life thoracic PVAT may have a distinct contribution to future cognition possibly due to its distinct adipose tissue type (brown fat) and anatomical proximity to the brain circulation.HighlightsHigher mid-life thoracic perivascular adipose tissue (thoracic PVAT) volume is related to a better future episodic memory in women. Higher mid-life thoracic PVAT radiodensity is related to worse future working and episodic memories. Negative association of high thoracic PVAT radiodensity with working memory is prominent at higher thoracic PVAT volume. Mid-life thoracic PVAT is linked to future memory loss, an early sign of Alzheimer's disease. Mid-life women's epicardial and paracardial fat are not related to future cognition.

Functional cognition is relevant for athletic success and interdependent with physical exercise, yet despite repeatedly demonstrated inflammatory responses to physical training, there are no studies addressing the relationship between cognition and inflammation in athletes. The aim of this study was to investigate the relationship between cognitive performance and selected inflammatory, and further physiological biomarkers in elite athletes. Data from 350 elite athletes regarding cognitive performance (processing speed, selective attention, working memory, cognitive flexibility), systemic inflammatory markers, metabolic hormones, growth factors, tissue damage markers, and micronutrients (e.g., ferritin, 25-OH-vitamin D), as well as physiological, subjective ratings of recovery and stress were analysed by correlative and multiple regression analyses. Results show that across all athletes variance in processing speed, selective attention, and working memory, could be best explained through a combination of metabolic hormones with physiological and psychological indicators of stress, and in cognitive flexibility through vitamin D levels. Only for the subgroup of athletes from closed-skill sports, the ratio TNF-α:IL-10 significantly contributed to explanation of variance in working memory and cognitive flexibility. In general, found correlations point to the importance of inflammatory balance and sufficient long-term nutrient supply for unaffected cognitive performance.

BackgroundThis study investigated the risk of diabetes by examining changes in memory, working memory, and processing speed among older adults to provide evidence on how each cognitive domain is associated with the risk of diabetes in older adults.MethodsThis study used Health and Retirement Study data and tracked the respondents from 2012 to 2020 (n = 5,748). The Telephone Interview for Cognitive Status-27 includes three cognitive tests (recall, seven subtraction, and counting backward tests) to assess each cognitive domain. A Cox proportional hazard regression was used to calculate the changes in the odds ratio (OR) of diabetes by increasing each cognitive function and the parameter in covariates.ResultsWe found that the OR of diabetes decreased with increasing universal cognitive function, increasing memory, working memory, and processing speed, and that age increased the OR in all analysis models.ConclusionThe findings of this study contribute to filling gaps in the literature by exploring: (a) the association between each cognitive function and the decline in diabetes risk and (b) the varying patterns of change in diabetes risk with increasing cognitive function.

IntroductionWe investigated associations between neighborhood racial/ethnic segregation and cognitive change.MethodsWe used data (n = 1712) from the Multi-Ethnic Study of Atherosclerosis. Racial/ethnic segregation was assessed using Getis-Ord (Gi*) z-scores based on American Community Survey Census tract data (higher Gi* = greater spatial clustering of participant's race/ethnicity). Global cognition and processing speed were assessed twice, 6 years apart. Adjusted multilevel linear regression tested associations between Gi* z-scores and cognition. Effect modification by race/ethnicity, income, education, neighborhood socioeconomic status, and neighborhood social support was tested.ResultsParticipants were on average 67 years old; 43% were White, 11% Chinese, 29% African American/Black, 17% Hispanic; 40% had high neighborhood segregation (Gi* > 1.96). African American/Black participants with greater neighborhood segregation had greater processing speed decline in stratified analyses, but no interactions were significant.DiscussionSegregation was associated with greater processing speed declines among African American/Black participants. Additional follow-ups and comprehensive cognitive batteries may further elucidate these findings.HighlightsA study of neighborhood racial/ethnic segregation and change in cognition. Study was based on a racially and geographically diverse, population-based cohort of older adults. Racial/ethnic segregation (clustering) was measured by the Getis-ord (Gi*) statistic. We saw faster processing speed decline among Black individuals in segregated neighborhoods.

Abstract Diminished cognitive and physical functions negatively affect the daily functions of individuals. Although combined cognitive and physical training prevents instrumental activities of daily living (IADL) disability in older adults, no predictive model or mediation analysis of IADL after combined training exists. This study aims to employ prediction and mediation analysis to identify the predictors of IADL performance and to elucidate the mediators of the association between baseline global cognition and subsequent IADL performance following combined cognitive and physical training. This study involved 177 participants aged 60 years and older who underwent combined training. Cognitive function was measured with the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Color Trails Test, Word List, and a dual task; physical function with the Timed Up and Go (TUG) test; daily function with the Lawton IADL Scale. We conducted regression analyses to identify the predictors of IADL performance, and mediation analysis to examine whether DSST and TUG mediate the relationship between MoCA and IADL. The pre-intervention DSST and TUG were significant independent predictors of post-intervention IADL. The association between the pre-intervention MoCA and post-intervention IADL was mediated by pre-intervention DSST and TUG. This study highlighted the importance of measuring and improving processing speed and functional mobility before and during interventions to enhance IADL outcomes. Trial registration: NCT03619577, 23/07/2018; NCT04689776, 29/12/2020.

Abstract Background Plasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations. Methods We examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61–73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter. Results After adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals. Conclusions These results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.

Abstract Advancing age is associated with declines in cognitive function. Although physical activity is thought to protect against this decline, it is unclear how a short-term uptake in daily steps or a decline in day-to-day step variability may contribute to cognition among older adults. We tested associations between changes in step counts, day-to-day step variability and executive cognitive functions among older adults taking part in a physical activity intervention. Thirty-seven older adults (33 females; 71.4 ± 6.3 years) completed a 10-week personalized physical activity intervention. Participants wore a Fitbit to measure daily step counts throughout the study. They also completed a computerized Stroop task before and after the intervention. Average step counts and step count variability via average-real-variability (ARV) were determined. Compared to pre-intervention, step counts increased (p

INTRODUCTION: We are developing the California Cognitive Assessment Battery (CCAB) to provide neuropsychological assessments to patients who lack test access due to cost, capacity, mobility, and transportation barriers. METHODS: The CCAB consists of 15 non-verbal and 17 verbal subtests normed for telemedical assessment. The CCAB runs on calibrated tablet computers over cellular or Wi-Fi connections either in a laboratory or in participants homes. Spoken instructions and verbal stimuli are delivered through headphones using naturalistic text-to-speech voices. Verbal responses are scored in real time and recorded and transcribed offline using consensus automatic speech recognition which combines the transcripts from seven commercial ASR engines to produce timestamped transcripts more accurate than those of any single ASR engine. The CCAB is designed for supervised self-administration using a web-browser application, the Examiner. The Examiner permits examiners to record observations, view subtest performance in real time, initiate video chats, and correct potential error conditions (e.g., training and performance failures, etc.,) for multiple participants concurrently. RESULTS: Here we describe (1) CCAB usability with older (ages 50 to 89) participants; (2) CCAB psychometric properties based on normative data from 415 older participants; (3) Comparisons of the results of at-home vs. in-lab CCAB testing; (4) We also present preliminary analyses of the effects of COVID-19 infection on performance. Mean z-scores averaged over CCAB subtests showed impaired performance of COVID+ compared to COVID- participants after factoring out the contributions of Age, Education, and Gender (AEG). However, inter-cohort differences were no longer significant when performance was analyzed with a comprehensive model that factored out the influences of additional pre-existing demographic factors that distinguished COVID+ and COVID- cohorts (e.g., vocabulary, depression, race, etc.,). In contrast, unlike AEG scores, comprehensive scores correlated significantly with the severity of COVID infection. (5) Finally, we found that scoring models influenced the classification of individual participants with Mild Cognitive Impairment (MCI, z-scores < -1.50) where the comprehensive model accounted for more than twice as much variance as the AEG model and reduced racial bias in MCI classification. DISCUSSION: The CCAB holds the promise of providing scalable laboratory-quality neurodiagnostic assessments to underserved urban, exurban, and rural populations.

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in regulating synaptic activity and plasticity.ObjectiveGiven that type-2 diabetes (T2DM) increases the risk of cognitive decline, and studies have suggested lower BDNF levels may be a risk factor of diabetic neurovascular complications, we sought to investigate total white matter hyperintensities (WMH) as a moderator of the effect of BDNF on hippocampal volume and cognition.MethodsOlder adults without dementia from the Alzheimer's Disease Neuroimaging Initiative (N = 454 including 49 with T2DM and 405 without diabetes) underwent neuropsychological evaluation, magnetic resonance imaging to quantify hippocampal and WMH volumes, and blood draw to assess BDNF.ResultsAdjusting for age, sex, and APOE ɛ4 carrier status, there was a significant interaction between total WMH and BDNF on bilateral hippocampal volume in the non-T2DM group (t = 2.63, p = 0.009). Examination of main effect models with a dichotomous high/low BNDF group revealed a significant main effect for low BDNF (t = -4.98, p

Introduction: Individuals with multiple sclerosis (MS) frequently experience visual and oculomotor symptoms that may impact and confound neuropsychological assessments of information processing speed (IPS). In this study, we examined the effect of the psychostimulant methylphenidate on oculomotor function and the association between change in oculomotor speed and change in information processing speed. Methods: We used a repeated measures crossover design in which a sample of 11 participants with MS were randomly assigned to one of two treatment arms: one that received methylphenidate for 4 weeks and another that received a placebo for 4 weeks. After a 7-day washout period, the treatments were crossed over. The King Devick test, the Symbol Digit Modalities Test, and the Paced Auditory Serial Addition Test were administered at baseline and after each of the two study arms. Results: We found a significant improvement in oculomotor speed in the methylphenidate condition as compared to placebo. This improvement was significantly correlated with improvement on a visuomotor assessment of IPS (Symbol Digit Modalities Test), but no such association was found for an auditory-verbal assessment of IPS (Paced Auditory Serial Addition Test). Discussion: These findings suggest that individuals with MS experience improved oculomotor speed while taking methylphenidate, which may, in turn, improve performance on assessments of IPS with visuomotor demands. [ABSTRACT FROM AUTHOR]

Background: Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes. Objectives: The study is to determine if HISCT can ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression, determine which specific areas of neurocognitive functioning are particularly vulnerable to SCD, and determine if there are age-related differences in neurocognitive functioning over time. Methods: We performed neurocognitive and neuroimaging in SCD recipients following HISCT. Children and adolescents with high-risk SCD who received parental HISCT utilizing CD34+ enrichment and mononuclear cell (T-cell) addback following myeloimmunoablative conditioning received cognitive evaluations and neuroimaging at three time points: pre-transplant, 1 and 2 years post-transplant. Results: Nineteen participants (13.1 ± 1.2 years [3.3-20.0]) received HISCT. At 2 years post-transplant, neuroimaging and cognitive function were stable. Regarding age-related differences pre-transplantation, older children (≥13 years) had already experienced significant decreases in language functioning (p < 0.023), verbal intelligence quotient (p < 0.05), non-verbal intelligence quotient (p < 0.006), and processing speed (p < 0.05), but normalized post-HISCT in all categories. Conclusion: Thus, HISCT has the potential to ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression. Further studies are required to determine if neurocognitive performance remains stable beyond 2 years post-HISCT. Clinical trial registration: The study was conducted under an investigator IND (14359) (MSC) and registered at clinicaltrials.gov (NCT01461837). [ABSTRACT FROM AUTHOR]

Background: Processing speed is a task-independent construct underpinning more complex goal-related abilities. Processing speed is impaired in alcohol dependence (AD) and is linked to relapse, as are the functions it underpins. Reliable measurement of processing speed may allow tracking of AD recovery trajectories and identify patients requiring additional support. Aims: To assess changes in reaction time (RT) from baseline (at the start of a detoxification programme) across early abstinence. Methods: Vibrotactile RT was assessed in early recovery between days 3 and 7 of treatment in 66 individuals with AD (25 females; aged 19–74, 44.60 ± 10.60 years) and against 35 controls tested on one occasion (19 females; 41.00 ± 13.60), using two multivariate multiple regressions. A mixed multivariate analysis of covariance (MANCOVA) of available AD data (n = 45) assessed change in RT between timepoints and between treatment settings (outpatient vs inpatient). Results: The group (AD vs control) significantly predicted choice RT at baseline and follow-up but did not significantly predict simple RT or RT variability, which is inconsistent with previous findings. At follow-up, mental fatigue was also predicted by the group, and MANCOVA indicated that this had worsened in inpatients but improved in outpatients. Conclusions: Recovery of RT measures so early in the treatment journey was not in line with previous research which indicates persisting deficits. The interaction between setting and timepoint indicates that despite being typically less medically complex, outpatients require ongoing support and monitoring during their recovery. [ABSTRACT FROM AUTHOR]

Psychomotor disturbance has been identified as a key feature of psychotic disorders, with motor signs observed in upwards of 66% of unmedicated, first-episode patients. Aberrations in the cerebellum have been directly linked to sensorimotor processing deficits including processing speed, which may underly psychomotor disturbance in psychosis, though these brain-behavior-symptom relationships are unclear, in part due to within-diagnosis heterogeneity across these levels of analysis. In 339 psychosis patients (242 schizophrenia-spectrum, 97 bipolar with psychotic features) and 217 controls, we evaluated the relationship between cerebellar grey matter volume in the Yeo sensorimotor network and psychomotor disturbance (mannerisms and posturing, retardation, excitement of the Positive and Negative Syndrome Scale [PANSS]), as mediated by processing speed (assessed via the SCIP). Models included intracranial volume, age, sex, and chlorpromazine equivalents as covariates. We observed significant mediation by processing speed, with a small positive effect of the cerebellum on processing speed (ß = 0.172, p = 0.029, d = 0.24) and a medium negative effect of processing speed on psychomotor disturbance (ß = −0.254, p < 0.001, d = 0.60), with acceptable specificity and sensitivity suggesting this model is robust against unmeasured confounding. The current findings suggest a critical role of cerebellar circuitry in a well-established sensorimotor aberration in psychosis (processing speed) and the presentation of related psychomotor phenotypes within psychosis. Establishing such relationships is critical for intervention research, such as TMS. Future work will employ more dimensional measures of psychomotor disturbance and cognitive processes to capture normative and aberrant brain-behavior-symptom relationships and may also determine the magnitude of these relationships within subtypes of psychosis (e.g., disorganized behavior, catatonia). [ABSTRACT FROM AUTHOR]

Background: Limited resources often hinder regular cognitive assessment of people with multiple sclerosis (pwMS) in standard clinical care. A self-administered iPad®-based cognitive screening-tool (Processing Speed Test; PST) might mitigate this problem. Objective: To evaluate the PST in clinical routine. Methods: We investigated the feasibility of the PST in both a quiet and a waiting room setting. We assessed the validity of the PST in comparison with the established Symbol Digit Modalities Test (SDMT). We explored associations between processing speed assessments and the Brief International Cognitive Assessment for MS (BICAMS), magnetic resonance imaging (MRI) parameters, and psychological factors. Additionally, we explored the ability of the PST to detect impairment in processing speed compared to the SDMT. Results: The PST was feasible in the waiting room setting. PST and SDMT correlated comparably with the BICAMS, MRI parameters, and psychological variables. Of 172 pwMS, 50 (30.8%) showed cognitive impairment according to the BICAMS; respective values were 47 (27.3%) for the SDMT and 9 (5.2%) for the PST. Conclusions: The PST performed in a waiting room setting correlates strongly with established cognitive tests. It thus may be used to assess processing speed in a resource-efficient manner and complement cognitive assessment in clinical routine. Despite comparable validity of the PST and SDMT, we identified more pwMS with impaired processing speed using normative data of the SDMT compared to the PST and advise caution, that the common cut-off score of – 1.5 SD from the current PST is not appropriate in Europe. [ABSTRACT FROM AUTHOR]

Recent studies suggest that the EEG aperiodic exponent (often represented as a slope in log–log space) is sensitive to individual differences in momentary cognitive skills such as selective attention and information processing speed. However, findings are mixed, and most of the studies have focused on just a narrow range of cognitive domains. This study used an archival dataset to help clarify associations between resting aperiodic features and broad domains of cognitive ability, which vary in their demands on momentary processing. Undergraduates (N = 166) of age 18–52 years completed a resting EEG session as well as a standardized, individually administered assessment of cognitive ability that included measures of processing speed, working memory, and higher‐order visuospatial and verbal skills. A subsample (n = 110) also completed a computerized reaction time task with three difficulty levels. Data reduction analyses revealed strong correlations between the aperiodic offset and slope across electrodes, and a single component accounted for ~60% of variance in slopes across the scalp, in both eyes‐closed and eyes‐open conditions. Structural equation models did not support relations between the slope and specific domains tapping momentary processes. However, secondary analyses indicated that the eyes‐open slope was related to higher overall performance, as represented by a single general ability factor. A latent reaction time variable was significantly inversely related to both eyes‐closed and eyes‐open resting exponents, such that faster reaction times were associated with steeper slopes. These findings support and help clarify the relation of the resting EEG exponent to individual differences in cognitive skills. This study is among the first to examine associations between the EEG aperiodic slope and cognitive performance as assessed by both validated clinical assessments and laboratory tasks in the same cohort. Results replicated prior findings that higher resting slopes are linked to faster reaction times. This association did not extend to individually‐administered tasks of clerical speed, working memory, or higher order visuospatial or verbal skills; however, the slope was related to a single general ability factor in the eyes‐open resting condition. [ABSTRACT FROM AUTHOR]

Objective: To determine the neurocognitive function of active professional male footballers, determine whether deficits/impairments exist, and investigate the association between previous concussion(s) and neurocognitive function. Methods: An observational cross-sectional study conducted via electronic questionnaires. The CNS Vital Signs online testing system was used to evaluate neurocognitive function. Results: Of the 101 participants, 91 completed the neurocognitive function testing. Neurocognitive function domain deficits or impairments were unlikely in 54.5–89.1%, slight in 5.9–21.8%, moderate in 1.0–9.9%, and likely in 4.0–14.9% of participants. A history of zero concussions found a significant association between the neurocognitive index (Odds Ratio [OR] 0.6; 95% CI 0.2–0.4) and complex attention domain (OR 0.3; 95% CI 0.1–0.9), with 40% and 70% less odds, respectively, of deficit/impairment. Among the 54.5% who reported any number of concussions, there were increased odds of neurocognitive domain deficits/impairments for complex attention (CA) [3.4 times more] and simple attention (SA) [3.1 times more]. Conclusion: In the active professional male footballer, most neurocognitive functions do not have significant deficits/impairments. The odds of neurocognitive function deficit/impairment were significantly increased threefold for CA and SA in those who reported a history of any concussion(s). [ABSTRACT FROM AUTHOR]

Objective: Increased intraindividual variability (IIV) of cognitive performance is a marker of cognitive decline in older adults. Whether computerized cognitive training (CCT) and aerobic exercise counteracts cognitive decline by reducing IIV is unknown. We investigated the effects of CCT with or without aerobic exercise on IIV in older adults. Methods: This was a secondary analysis of an 8-week randomized controlled trial. Older adults (aged 65–85 years) were randomized to CCT alone (n = 41), CCT with aerobic exercise (n = 41), or an active control group (n = 42). The CCT group trained using the Fit Brains® platform 3×/week for 1 hr (plus 3×/week of home-based training). The CCT with aerobic exercise group received 15 min of walking plus 45 min of Fit Brains® 3×/week (plus 3×/week of home-based training). The control group received sham exercise and cognitive training (3×/week for 1 hr). We computed reaction time IIV from the Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test (Flanker), and Pattern Comparison Processing Speed Test (PACPS). Results: Compared with the control group, IIV reduced in a processing speed task (PACPS) following CCT alone (mean difference [95% confidence interval]: −0.144 [−0.255 to −0.034], p < 0.01) and CCT with aerobic exercise (−0.113 [−0.225 to −0.001], p < 0.05). Attention (Flanker congruent) IIV was reduced only after CCT with aerobic exercise (−0.130 [−0.242 to −0.017], p < 0.05). Conclusions: A CCT program promoted cognitive health via reductions in IIV of cognitive performance and combining it with aerobic exercise may result in broader benefits. [ABSTRACT FROM AUTHOR]

Introduction Mild traumatic brain injury (mTBI), depression, and PTSD are highly prevalent in post-9/11 veterans. With the comorbidity of depression and PTSD in post-9/11 veterans with mTBI histories and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. We sought to examine neuropsychological correlates of PTSD and depressive symptom improvement in veterans with a history of mTBI who received CCT. Materials and Methods Thirty-seven post-9/11 veterans with mTBI histories and cognitive complaints received 10 weekly 120-minute CCT group sessions. Participants completed a baseline neuropsychological assessment, including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD and depression) at baseline, post-treatment, and a 5-week follow-up. Paired samples t -tests were used to examine statistically significant changes in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson's correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores were entered as independent variables in multivariable regression analyses to examine their association with symptom change at post-treatment and follow-up. Results Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (≥17.5% score reduction), and over 20% had clinically meaningful improvement in PTSD symptoms (≥10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on Trail-Making Number-Letter Switching was also associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed that worse processing speed and worse aspects of executive functioning at baseline were associated with depressive symptom improvement at post-treatment and follow-up. Conclusions Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve. [ABSTRACT FROM AUTHOR]

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition. [ABSTRACT FROM AUTHOR]

Habituation and dishabituation are the most prevalent measures of infant cognitive functioning, and they have reliably been shown to predict later cognitive outcomes. Yet, the exact mechanisms underlying infant habituation and dishabituation are still unclear. To investigate them, we tested 106 8‐month‐old infants on a classic habituation task and a novel visual learning task. We used a hierarchical Bayesian model to identify individual differences in sustained attention, learning performance, processing speed and curiosity from the visual learning task. These factors were then related to habituation and dishabituation. We found that habituation time was related to individual differences in processing speed, while dishabituation was related to curiosity, but only for infants who did not habituate. These results offer novel insights in the mechanisms underlying habituation and serve as proof of concept for hierarchical models as an effective tool to measure individual differences in infant cognitive functioning. Research Highlights: We used a hierarchical Bayesian model to measure individual differences in infants' processing speed, learning performance, sustained attention, and curiosity.Faster processing speed was related to shorter habituation time.High curiosity was related to stronger dishabituation responses, but only for infants who did not habituate. [ABSTRACT FROM AUTHOR]

We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA. Methods: We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences. Results: We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.β = 1.4[95%CI:0.6–2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1–2.9]; presymptomatic D-CAA:1.2[0.1–2.2], control median:0[IQR:0–3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.β=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.β=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women. Discussion: According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately. [ABSTRACT FROM AUTHOR]

The acquisition of skills, such as learning to play a musical instrument, involves various phases that make specific demands on the learner. Knowledge of the cognitive and motor contributions during learning phases can be helpful in developing effective and targeted interventions for healthy aging. Eighty-six healthy older participants underwent an extensive cognitive, motoric, and musical test battery. Within one session, one piano-related and one music-independent movement sequence were both learned. We tested the associations between skill performance and cognito-motor abilities with Bayesian mixed models accounting for individual learning rates. Results showed that performance was positively associated with all cognito-motor abilities. Learning a piano-related task was characterized by relatively strong initial associations between performance and abilities. These associations then weakened considerably before increasing exponentially from the second trial onwards, approaching a plateau. Similar performance–ability relationships were detected in the course of learning a music-unrelated motor task. Positive performance–ability associations emphasize the potential of learning new skills to produce positive cognitive and motor transfer effects. Consistent high-performance tasks that demand maximum effort from the participants could be very effective. However, interventions should be sufficiently long so that the transfer potential can be fully exploited. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) represents a promising behavioral approach for managing cognitive dysfunction in multiple sclerosis (MS). However, there is a lack of information on the pattern of free-living PA intensity (e.g., step rate) and its unique association with cognition. Such information is essential for informing clinical trials in MS. Objective: We examined associations among PA volume and intensity with cognitive function in persons with MS, and intensity was derived from steps-based metrics (peak 30-min cadence [Peak-30CAD], and time spent in incremental cadence bands). Methods: We included data from 147 persons with MS who underwent assessments of cognitive function (via Brief International Cognitive Assessment in MS) and wore an ActiGraph GT3X + accelerometer for 7 days. We performed bivariate and partial correlations and regression analyses examining associations among PA metrics and cognitive outcomes. Results: Higher Peak-30CAD was significantly associated with better performance in cognitive processing speed and verbal learning and memory (rs = 0.19–0.38), and the associations remained significant when controlling for daily steps, age, sex, and years of education (p < 0.05). By comparison, daily steps was only correlated with cognitive processing speed (rs = 0.26), and the association was non-significant when controlling for Peak-30CAD and covariates. There were stronger correlations among time spent in higher intensity cadence bands with cognitive performance (rs = 0.18–0.38). Conclusion: Our results highlight the important role of PA intensity for cognition in MS, and may inform future development of focal PA interventions that focusing on step rate patterns for improving cognition in persons with MS. [ABSTRACT FROM AUTHOR]

Children with gifted intellects often earn lower scores on measures of processing speed than their nongifted counterparts. However, neuropsychological research indicates such a profile of scores is likely not due to a true innate neurocognitive processing speed deficit but is rather a statistical artifact resulting from the interference of common cognitive and behavioral idiosyncrasies inherent to giftedness, such as perfectionism and an aversion to completing paper and pencil tasks. The first aim of this study is to identify and explain the relative underperformance of children with gifted intellects on measures of processing speed. The second aim is to develop a neuropsychologically informed framework for clinically assessing processing speed in children with gifted intellects using alternative measures from the WISC–V. Clinical implications are discussed as they relate to the relative disabling effects of common gifted-related idiosyncrasies on the expression of their otherwise intact neuropsychological capabilities. [ABSTRACT FROM AUTHOR]

Developmental dyslexia and attention-deficit/hyperactivity disorder (ADHD) co-occur in 15–40% of individuals diagnosed with one disorder. Despite substantial research on the cognitive profiles of preschoolers at risk for either dyslexia or ADHD, studies have neglected children at risk for co-occurring dyslexia and ADHD. Thus, our study compared the cognitive profile of preschoolers at risk for dyslexia with the profile of children at risk for co-occurring dyslexia and ADHD. We assessed 50 preschoolers at dyslexia risk (DR), 50 at dyslexia + ADHD risk (DAR), and 48 without risk (NR) (Mage = 67 months). Our assessment encompassed phonological processing, executive functioning (EF), receptive vocabulary, and processing speed. Principal component analysis revealed two distinct components within the measures of EF, a verbal short-term memory and an EF component. ANOVA revealed that the NR group outperformed risk groups across measures, except for cognitive flexibility and delay of gratification. Notably, the DR and DAR groups did not differ in most measures but showed near-significant differences on the EF component, with the DR group having higher composite scores than the DAR group. In conclusion, ADHD risk did not impact the cognitive performance of children at risk for dyslexia but might amplify EF problems that at-risk preschoolers encounter. [ABSTRACT FROM AUTHOR]

Background and Objectives Purpose in life is associated with healthier cognitive outcomes in older adulthood. This research examines within-person dynamics between momentary purpose and cognitive function to provide proof of concept that increases in purpose are associated with better cognitive performance. Research Design and Methods Participants (N  = 303; 54% female; M age = 51.71, SD  = 7.32) completed smartphone-based momentary assessments of purpose and short cognitive tasks 3 times a day for 8 days. Results In moments when participants felt more purpose driven than their average, they had faster processing speed (b  = −1.240, SE  = 0.194; p  < .001), independent of person, temporal, and contextual factors and practice effects. Momentary purpose was unrelated to visual working memory performance (b  = −0.001, SE  = 0.001; p  = .475). In contrast to purpose, momentary hedonic affect (e.g. happiness) was unrelated to momentary cognition. Discussion and Implications Feeling more momentary purpose may support faster processing speed in daily life. Such evidence provides stage 0 support for a purpose-based intervention for healthier cognition, which may be particularly useful in middle adulthood and the transition to older adulthood before the onset of cognitive impairment. [ABSTRACT FROM AUTHOR]

BackgroundModerate to severe traumatic brain injury (TBI) often results in cognitive deficits. Processing speed (PS) deficits are common, exerting a significant impact on daily life. Few studies have examined the efficacy of cognitive rehabilitation specifically for PS deficits in moderate to severe TBI.ObjectiveExamine the efficacy of Speed of Processing Training (SOPT) in moderate to severe TBI. This protocol is a 10-session behavioral intervention for PS deficits that has been successfully used with other cognitively impaired populations.MethodsThis double-blind, placebo-controlled, randomized clinical trial included 46 participants with moderate to severe TBI, 22 randomly assigned to the treatment group and 24 to the placebo-control group. Baseline and follow-up measures included a task similar to the training task (UFOV), measures of near transfer (neuropsychological measures of processing speed: Symbol Digit Modalities Test (SDMT), Wechsler Adult Intelligence Scale-IV (WAIS-IV) Symbol Search, WAIS-IV Coding) and measures of far transfer [neuropsychological measures of learning and memory: the California Verbal Learning Test-II (CVLT-II), Memory Assessment Scales - Prose Memory (MAS-PM)].ResultsSignificant improvement from pre-to post-SOPT was observed on all subtests of the UFOV, which is similar to the training task. There was no significant difference on neuropsychological measures of PS or new learning and memory post-treatment. Neuropsychological assessment 6-months post-treatment showed no significant change in PS ability over time. Monthly booster sessions did not impact performance at the 6-month follow-up.ConclusionConsistent with the SOPT literature, SOPT improves PS ability as measured by the UFOV, a task similar to the training task, in moderate to severe TBI. However, neither near nor far transfer was noted. That is, no improvement was noted on neuropsychological measures of PS.

ObjectiveChronic inflammation and vascular dysfunction (e.g., chronic endothelial activation) are related yet dissociable mechanisms of HIV-associated neurocognitive impairment (NCI), even among those on antiretroviral therapy (ART). However, how these mechanisms differentially contribute to domain-specific deficits in people with and without HIV (PWH, PWoH) is unclear. We empirically-derived profiles of NCI and examined relationships with peripheral inflammatory and vascular biomarkers.MethodsParticipants were 84 virally-suppressed PWH and 126 PWoH who underwent neuropsychological testing and blood draw. Cluster analysis identified subgroups based on domain deficit scores. ANOVAs examined HIV serostatus and cluster group differences in composite plasma biomarker z-scores of inflammation (IL-6, CXCL10/IP-10, CCL2/MCP-1) and vascular injury (VCAM-1, ICAM-1, uPAR). Confirmatory regressions examined the interaction of HIV and biomarker z-scores on domain-specific T-scores, controlling for cardiovascular disease (CVD) risk and psychosocial factors.ResultsCluster analysis identified three groups: Unimpaired (n = 129), Learning/Recall (n = 52, isolated learning/recall deficits), Dysexecutive/Slow (n = 29, executive function, working memory, processing speed, and motor deficits). PWH had higher odds of Dysexecutive/Slow membership, which related to CVD risk and higher vascular dysfunction, but not inflammation, in PWH. Vascular biomarkers moderated adverse HIV effects on executive function, processing speed, and working memory such that PWH had lower T-scores only when vascular dysfunction was high.ConclusionsIn PWH with controlled disease, peripheral markers of endothelial dysfunction and vascular permeability are selectively associated with an empirically-derived subgroup that exhibits domain deficits commonly impacted by cerebrovascular disease. Findings support the presence of a vascular NCI subgroup of PWH who may benefit from interventions that directly target the neurovascular unit.

Ralph HB Benedict,1 Pamela Vo,2 Nicholas Adlard,2 Olwyn Grennan,3 Ashley Enstone,4 Daisy Bridge,4 Robin Wyn,4 Stanley L Cohan5 1Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Ireland, Dublin, Ireland; 4Adelphi Values PROVE, Bollington, UK; 5Providence Brain and Spine Institute, Providence St. Joseph Health, Portland, OR, USACorrespondence: Pamela Vo, Email pamela.vo@novartis.comIntroduction: Cognitive impairment, especially relating to cognitive processing speed, is a major cause of disability in people with multiple sclerosis (MS). Utility values are quantitative estimates of the quality of life experienced in specific health states and are a key component of cost-effectiveness modelling. However, existing health state utility values in MS typically focus on physical ability and are generally derived using generic (not disease-specific) measures of quality of life. The objective of the current study was to generate health state utility values for levels of cognitive impairment. We used a direct utility elicitation approach called the time trade-off (TTO) methodology.Materials and Methods: Health state descriptions were created following interviews with healthcare professionals, patients, and caregivers in the United States (n=35), and with healthcare professionals in the UK (n=5). Three health states (mild, moderate, and severe impairment) were defined based upon a well-established and validated test for cognitive dysfunction called the Symbol Digit Modalities Test (SDMT) and described using qualitative interview findings. Next, interviews with members of the general public in the UK were conducted to estimate utility values for each health state using the TTO methodology. The procedure was based on the established Measurement and Valuation of Health (MVH) protocol, which generates values on a scale from 0.0 to 1.0.Results: Mean health state utility values were 0.77 ± 0.24 in “mild impairment” (SDMT 43-40), 0.57 ± 0.26 in “moderate impairment” (SDMT 39-32), and 0.34 ± 0.28 in “severe impairment” (SDMT ≤ 31).Discussion: Results indicate that the public perceives that health states of cognitive slowing (as observed in MS) are associated with a substantial reduction in affected individuals’ health-related quality of life, quantified using the TTO methodology. Future economic modeling should consider how utility impacts of both cognitive and physical disability can be appropriately incorporated.Keywords: cognitive impairment, processing speed, health state utility, health-related quality of life, multiple sclerosis, time trade-off

The Trail Making Test (TMT) is one of the most commonly administered tests in clinical and research neuropsychological settings. The two parts of the test (part A (TMT-A) and part B (TMT-B)) enable the evaluation of visuoperceptual tracking and processing speed (TMT-A), as well as divided attention, set-shifting and cognitive flexibility (TMT-B). The main cognitive processes that are assessed using TMT, i.e., processing speed, divided attention, and cognitive flexibility, are often affected in patients with stroke. Considering the wide use of TMT in research and clinical settings since its introduction in neuropsychological practice, the purpose of our review was to provide a comprehensive overview of the use of TMT in stroke patients. We present the most representative studies assessing processing speed and attentional shift/mental flexibility in stroke settings using TMT and applying scoring methods relying on conventional TMT scores (e.g., time-to-complete part A and part B), as well as derived measures (e.g., TMT-(B-A) difference score, TMT-(B/A) ratio score, errors in part A and part B). We summarize the cognitive processes commonly associated with TMT performance in stroke patients (e.g., executive functions), lesion characteristics and neuroanatomical underpinning of TMT performance post-stroke, the association between TMT performance and patients’ instrumental activities of daily living, motor difficulties, speech difficulties, and mood statue, as well as their driving ability. We also highlight how TMT can serve as an objective marker of post-stroke cognitive recovery following the implementation of interventions. Our comprehensive review underscores that the TMT stands as an invaluable asset in the stroke assessment toolkit, contributing nuanced insights into diverse cognitive, functional, and emotional dimensions. As research progresses, continued exploration of the TMT potential across these domains is encouraged, fostering a deeper comprehension of post-stroke dynamics and enhancing patient-centered care across hospitals, rehabilitation centers, research institutions, and community health settings. Its integration into both research and clinical practice reaffirms TMT status as an indispensable instrument in stroke-related evaluations, enabling holistic insights that extend beyond traditional neurological assessments.

OBJECTIVES: Late Life Depression (LLD) is associated with persistent cognitive dysfunction even after depression symptoms improve. The present study was designed to examine cognitive outcomes associated with the pattern of depression severity change during psychotherapy intervention for LLD. METHODS: 96 community-dwelling adults ages 65-91 with major depressive disorder completed 12 sessions of Problem-Solving Therapy at the University of California, San Francisco. Nonlinear trajectories of depression severity ratings using the Hamilton Depression Rating Scale were computed from multiple time points collected throughout the weekly psychotherapy intervention. Performance on measures of cognition (information processing speed, executive functioning, verbal learning, memory) was assessed at baseline and post-treatment. Linear mixed-effects models examined associations between nonlinear depression severity trajectories and post-treatment change in cognitive performance. RESULTS: Broadly, different patterns of depression change during treatment were associated with improved cognition post-treatment. Greater and more consistent interval improvements in depression ratings were differentially associated with improvements in aspects of verbal learning, memory, and executive function post-treatment, while no associations were found with information processing speed. CONCLUSIONS: The heterogeneity of depression trajectories associated with improved cognitive outcomes suggests that the temporal pattern of depression response may impact specific cognitive processes distinctly. Results suggest that use of nonlinear depression severity trajectories may help to elucidate complex associations between the time course of depression response and cognitive outcomes of psychotherapy in LLD. These findings have important implications for identifying treatment targets to enhance clinical and cognitive outcomes of psychotherapy in LLD.

AbstractPurposeMethodsResultsConclusionOff-topic verbosity (OTV) is a tendency towards excessive, off-topic speech and has been linked with age-related deficits in executive functioning, particularly inhibition. However, there are numerous disagreements within the literature on what constitutes OTV, and there is a further lack of investigation into alternative cognitive explanations for the link between inhibition and OTV. The purpose of this study was to investigate the speech characteristics of OTV in young and older adults as well as to examine whether variations in OTV are better explained by diminished executive functioning or processing speed, as measured by the D-KEFS Stroop test.Young adults (n = 65; age 18–28) and older adults (n = 85; age 60–98) completed the D-KEFS Color-Word Interference Test and provided verbal samples of autobiographical episodic and procedural speech. These speech samples were rated on three facets of OTV: tangentiality, egocentrism and quantity of speech.Procedural autobiographical speech was found to best measure age cohort variations in OTV, and higher OTV was associated with poorer Stroop test performance in older adults but not in young adults. In fact, young adults only displayed associations between poorer Stroop performance and a reduction in speech quantity. Finally, processing speed deficits were more associated with increased OTV in older adults than executive functioning.These results provide support for links between age-related cognitive decline and OTV, but the results suggest that processing speed may be more implicated than executive functioning. [ABSTRACT FROM AUTHOR]

Deficits in working memory (WM) and processing speed (PS) are thought to undermine other cognitive functions in de novo Parkinson's disease (dnPD). However, these interrelationships are only partially understood. This study investigated whether there are stronger relationships between verbal WM and verbal episodic memory encoding and retrieval, whether verbal WM and PS have a greater influence on other aspects of cognitive functioning, and whether the overall strength of interrelationships among several cognitive functions differs in dnPD compared to health. Data for 198 healthy controls (HCs) and 293 dnPD patients were analysed. Participants completed a neuropsychological battery probing verbal WM, PS, verbal episodic memory, semantic memory, language and visuospatial functioning. Deficit analysis, network modelling and graph theory were combined to compare the groups. Results suggested that verbal WM performance, while slightly impaired, was more strongly associated with measures of verbal episodic memory encoding and retrieval, as well as other measured cognitive functions in the dnPD network model compared to the HC network model. PS task performance was impaired and more strongly associated with other neuropsychological task scores in the dnPD model. Associations among task scores were stronger overall in the dnPD model. Together, these results provide further evidence that WM and PS are important influences on the other aspects of cognitive functioning measured in this study in dnPD. Moreover, they provide novel evidence that verbal WM and PS might bear greater influence on the other measured cognitive functions and that these functions are more strongly intertwined in dnPD compared to health. [ABSTRACT FROM AUTHOR]

Objectives: Cognitive impairment is a core feature of bipolar disorder (BD) and major depressive disorder (MDD). Deficits in processing speed (PS) and sustained attention (SA) may be particularly impaired and may underpin a broader profile of deficits, however current knowledge of the nature of these impairments is limited by heterogeneous results in the literature. Few reviews to date have attempted to disentangle sources of heterogeneity to assess the presence and magnitude of impairments in PS and SA in BD and MDD. Methods: One hundred and three studies were reviewed to examine performance in tests of PS and SA in BD (n = 3452) and MDD (n = 5461) compared to healthy controls (n = 8016). Neuropsychological methodology used in the literature was summarised. Data were meta-analysed to assess impairments in PS and SA for each neuropsychological test separately. Subgroup analysis was performed across mood states to investigate sources of heterogeneity. Results: Impairments were found across most neuropsychological tests, with small to large effect sizes for BD (range: d = 0.19-0.96) and MDD (range: d = 0.29-0.86). Impairments were present in symptomatic states and euthymia in most cases. Some outcome measures were not impaired in euthymia. Heterogeneity was observed for most neuropsychological tests and remained after separating by mood state. There inadequate data to meta-analyse some outcome measures, particularly for symptomatic groups. Conclusion: Impairments in PS and SA in BD and MDD can be observed across most neuropsychological tests. Future research should further investigate the nature of these impairments across mood states, controlling for clinical confounds. [ABSTRACT FROM AUTHOR]

Children with sickle cell disease (SCD) may experience cognitive difficulties, including slowed processing speed. Thus, we investigated if processing speed changes over time. From 1992–2001, 103 participants with SCD aged 3–16 years (n ≤ 8.99 = 45; n ≥ 9.00 = 58) completed cognitive assessments. MRI was available for 54 participants. Between 1992–2002, 58 participants consented to one or two further assessments. A repeated measures regression using linear mixed-effects modelling determined longitudinal changes in processing speed index (PSI), examining the interaction between age (continuous variable) and timepoint (i.e., assessment 1 or 3) and controlling for MRI infarct status (i.e., no infarct, silent infarct, or stroke). Those aged ≤8.99 and ≥9.00 at first assessment experienced PSI decline. Declines were most prominent for the processing speed coding subtest, with a significant interaction between timepoint and age, t(31) = 2.64, p = 0.01. This decline may reflect a developmental delay, likely due to disease progression, with slower improvements in processing speed. Although there have been significant improvements in SCD treatments, mostly in high-income countries, processing speed still remains a target; thus, incorporating clinical monitoring of processing speed may help identify delay and allow for early intervention. [ABSTRACT FROM AUTHOR]

Introduction: There is a paucity of clinical studies examining the long-term effects of vagus nerve stimulation (VNS) on cognition, although a recent study of patients with drug-resistant epilepsy (DRE) treated with VNS therapy demonstrated significant improvement in executive functions as measured by the EpiTrack composite score. The present study aimed to investigate performance variability in three cognitive tests assessing executive functions and working memory in a cohort of DRE patients receiving VNS therapy during a follow-up duration of up to 5 years. Methods: The study included 46 DRE patients who were assessed with the Trail Making Test (TMT) (Parts A and B) and Digit Span Backward (DB) task prior to VNS implantation, 6 months and 12 months after implantation, and yearly thereafter as a part of the clinical VNS protocol. A linear mixed-effects (LME) model was used to analyze changes in test z scores over time, accounting for variations in follow-up duration when predicting changes over 5 years. Additionally, we conducted descriptive analyses to illustrate individual changes. Results: On average, TMT-A z scores improved by 0.024 units (95% confidence interval (CI): 0.006 to 0.042, p = 0.009), TMT-B z scores by 0.034 units (95% CI: 0.012 to 0.057, p = 0.003), and DB z scores by 0.019 units per month (95% CI: 0.011 to 0.028, p < 0.001). Patients with psychiatric comorbidities achieved the greatest improvements in TMT-B and DB z scores among all groups (0.0058 units/month, p = 0.036 and 0.028 units/month, p = 0.003, respectively). TMT-A z scores improved the most in patients taking 1-2 ASMs as well as in patients with psychiatric comorbidities (0.042 units/month, p = 0.002 and p = 0.003, respectively). Conclusion: Performance in all three tests improved at the group level during the follow-up period, with the most robust improvement observed in TMT-B, which requires inhibition control and set-switching in addition to the visuoperceptual processing speed that is crucial in TMT-A and working-memory performance that is essential in DB. Moreover, the improvement in TMT-B was further enhanced if the patient had psychiatric comorbidities. [ABSTRACT FROM AUTHOR]

Memory problems are among the most frequently reported cognitive complaints by individuals with an acquired brain injury (ABI). Processing speed and working memory deficits are often the result of ABI. These cognitive deficits significantly impact the acquisition and retention of information necessary for memory formation. This study investigated the influence of processing speed and working memory on immediate and delayed recall for verbal and visual memory, as well as overall memory recall in adults living with a chronic ABI. Sixty-three participants living with a chronic ABI, who were at least one-year post-injury, were cognitively assessed with the CNS-Vital Signs (CNS-VS) computerized cognitive battery and Wechsler Test of Adult Reading. The CNS-VS Processing Speed significantly predicted delayed recall for verbal memory and overall memory performance. The CNS-VS Working Memory was not a significant predictor of memory recall. Processing speed deficits negatively impact memory in individuals with a chronic ABI. These findings suggest the memory recall of adults with a chronic ABI is associated with poor processing speed and poor acquisition of information. Therefore, cognitive rehabilitation that improves processing speed should be the focus for individuals with ABI to improve memory performance as well as impaired processing speed. [ABSTRACT FROM AUTHOR]

Cognitive disengagement syndrome (CDS), previously termed sluggish cognitive tempo (SCT), is characterized by excessive daydreaming, mental confusion, and slowed behavior or thinking. Prior research has found inconsistent relations between CDS and neurocognition, though most studies have used small or ADHD-defined samples, non-optimal measures of CDS, and/or examined limited neurocognitive domains. Accordingly, this study examined the association of parent- and teacher-reported CDS symptoms using a comprehensive neurocognitive battery in a sample of 263 children (aged 8–12) selected with a range of CDS symptomatology. Parents and teachers provided ratings of CDS and ADHD inattentive (ADHD-IN) symptoms. Path analyses were conducted to examine CDS and ADHD-IN as unique predictors of neurocognitive functioning after covarying for age, sex, and family income. CDS symptoms were uniquely associated with slower performance across a range of cognitive domains, including verbal inhibition, rapid naming/reading, planning, divided attention, and set shifting. In contrast, ADHD-IN symptoms were uniquely associated with poorer performance on a Go/NoGo task (inhibition/distractibility), visual scanning and discrimination, and interference control. Findings from the current study, amongst the first to recruit children based on levels of CDS symptomatology, provide the strongest evidence to date that the neurocognitive phenotype of CDS is characterized by slowed cognitive processing, and add to its validity as a separate syndrome from ADHD. If replicated, these findings have implications for assessment, treatment, and school accommodations for CDS. Neuroimaging studies exploring the neurobiological basis of CDS are also needed. [ABSTRACT FROM AUTHOR]

Introduction: In this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia. Methods: The Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome. Results: One hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome. Conclusions: Our results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation. [ABSTRACT FROM AUTHOR]

Objective: The Exercise Program in Cancer and Cognition Study was a randomized controlled trial designed to determine whether 6 months of moderate‐intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET). Methods: Postmenopausal women with hormone receptor+, early‐stage BC, within two years post‐primary therapy were randomized to the exercise intervention (six months, ≥150 min of moderate‐intensity aerobic exercise/week) or usual care control condition. Outcomes were assessed at pre‐randomization and after intervention completion. Groups were compared using linear mixed‐effects modeling. Results: Participants (N = 153) were X‾ $\overline{X}$ = 62.09 ± 8.27 years old, with stage I BC (64.1%) and a median of 4.7 months post‐diagnosis. We found a group‐by‐time interaction (p = 0.041) and a trend for the main effect of time (p = 0.11) for processing speed with improved performance in the exercise group and no change in the controls. Similar main effects of time were observed for learning and memory (p = 0.024) and working memory (p = 0.01). Better intervention adherence was associated with improved processing speed (p = 0.017). Conclusions: Six months of moderate‐intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within 2 years of completing primary therapy (surgery +/− chemotherapy). This is the first large‐scale study to examine the effects of aerobic exercise on neurocognitive function in women with BC. Additional research is needed to address the long‐term effects of aerobic exercise on cognitive function. [ABSTRACT FROM AUTHOR]

The Trail Making Test (TMT) is one of the most commonly administered tests in clinical and research neuropsychological settings. The two parts of the test (part A (TMT-A) and part B (TMT-B)) enable the evaluation of visuoperceptual tracking and processing speed (TMT-A), as well as divided attention, set-shifting and cognitive flexibility (TMT-B). The main cognitive processes that are assessed using TMT, i.e., processing speed, divided attention, and cognitive flexibility, are often affected in patients with stroke. Considering the wide use of TMT in research and clinical settings since its introduction in neuropsychological practice, the purpose of our review was to provide a comprehensive overview of the use of TMT in stroke patients. We present the most representative studies assessing processing speed and attentional shift/mental flexibility in stroke settings using TMT and applying scoring methods relying on conventional TMT scores (e.g., time-to-complete part A and part B), as well as derived measures (e.g., TMT-(B-A) difference score, TMT-(B/A) ratio score, errors in part A and part B). We summarize the cognitive processes commonly associated with TMT performance in stroke patients (e.g., executive functions), lesion characteristics and neuroanatomical underpinning of TMT performance post-stroke, the association between TMT performance and patients' instrumental activities of daily living, motor difficulties, speech difficulties, and mood statue, as well as their driving ability. We also highlight how TMT can serve as an objective marker of post-stroke cognitive recovery following the implementation of interventions. Our comprehensive review underscores that the TMT stands as an invaluable asset in the stroke assessment toolkit, contributing nuanced insights into diverse cognitive, functional, and emotional dimensions. As research progresses, continued exploration of the TMT potential across these domains is encouraged, fostering a deeper comprehension of post-stroke dynamics and enhancing patient-centered care across hospitals, rehabilitation centers, research institutions, and community health settings. Its integration into both research and clinical practice reaffirms TMT status as an indispensable instrument in stroke-related evaluations, enabling holistic insights that extend beyond traditional neurological assessments. [ABSTRACT FROM AUTHOR]

This study aimed to examine the relationships among cognitive function, symptoms, prefrontal activation, basic driving skills, and collision risk factors using a hazard prediction task in simulated driving. Participants included 42 people with schizophrenia aged 20–50 years who had actual experience of driving. The Trail making test (TMT) A and TMT B, Wechsler Memory Test–Revised (WMS-R), and Zoo Map test (ZMT) were used to evaluate cognitive function. Positive and negative syndrome scale was used to assess symptoms, and brain activity was assessed by evaluating cerebral blood flow during a visual working memory task using functional near-infrared spectroscopy. Driving tasks that tested basic skills, such as brake reaction, steering wheel skills, and standard deviation of lateral position, were analyzed using multiple regression analysis. Three hazard prediction tasks were performed using discriminant analysis. Brake reaction associated with cerebral blood flow and TMT-A. Steering wheel skills associated with WMS-R, driving experience and depression. Significant differences were found between the collision and noncollision groups in the hazard prediction task, as shown by the ZMT, driving experience, and brake reaction. Brain activity in the frontal lobe during a desk task may be useful data for driving assessment. Assessment of processing speed and learning ability may be particularly important in the evaluation of basic skills for safe driving. In addition, for people with schizophrenia, foresight, as represented by proactive planning, experience, and quick braking may be an essential characteristic to anticipate danger and react quickly enough to avoid collisions. [ABSTRACT FROM AUTHOR]