OBJECTIVE: Recent preventative approaches with young people at clinical high risk for psychosis (CHR-P) have focused on the remediation of the cognitive deficits that are readily apparent and predictive of future illness. However, the small number of trials using cognitive remediation with CHR-P individuals have reported mixed results. The proposed 2-phased study will test an innovative internet-based and remotely-delivered Specific COgnitive REmediation plus Surround (or SCORES) intervention that targets early processing speed deficits in CHR-P adolescents aged 14-20 years old.
METHODS: In the first R61 phase, a single-arm 2-year proof of concept study, 30 CHR-P individuals will receive SCORES for 10 weeks (4 h per week/40 h total) with a midpoint assessment at 20 h (5 weeks) to demonstrate target engagement and identify the optimal dose needed to engage the target. The Go/No-Go criteria to move to the R33 phase will be processing speed scores improving by a medium effect size (Cohen\'s d ≥ .6). The proposed package includes a set of complimentary support surround procedures to increase enjoyment and ensure that participants will complete the home-based training. In the second R33 phase, a 3-year pilot study, we will replicate target engagement in a new and larger sample of 54 CHR-P individuals randomized to SCORES (optimized dose) or to a video game playing control condition. In addition, the R33 phase will determine if changes in processing speed are associated with improved social functioning and decreasing attenuated positive symptoms. The support surround components of the intervention will remain constant across phases and conditions in the R33 phase to firmly establish the centrality of processing speed training for successful remediation.
CONCLUSIONS: The SCORES study is a completely virtual intervention that targets a core cognitive mechanism, processing speed, which is a rate-limiting factor to higher order behaviours and clinical outcomes in CHR-P adolescents. The virtual nature of this study should increase feasibility as well improve the future scalability of the intervention with considerable potential for future dissemination as a complete treatment package.

OBJECTIVE: 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.
UNASSIGNED: This was a cross-sectional, secondary analysis of baseline data from a randomized controlled trial, the Exercise Program in Cancer and Cognition Study.
UNASSIGNED: 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.
CONCLUSIONS: Gene methylation variations were demonstrated, suggesting the genes\' potential roles and two possible distinct mechanisms of cognitive function in cancer. .

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].
CONCLUSIONS: 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).

BACKGROUND: Although a growing body of literature documents the importance of neighborhood effects on late-life cognition, little is known about the relative strength of objective and subjective neighborhood measures on late-life cognitive changes. This study examined effects of objective and subjective neighborhood measures in three neighborhood domains (neighborhood safety, physical disorder, food environments) on longitudinal changes in processing speed, an early marker of cognitive aging and impairment.
METHODS: The analysis sample included 306 community-dwelling older adults enrolled in the Einstein Aging Study (mean age = 77, age range = 70 to 91; female = 67.7%; non-Hispanic White: 45.1%, non-Hispanic Black: 40.9%). Objective and subjective measures of neighborhood included three neighborhood domains (i.e., neighborhood safety, physical disorder, food environments). Processing speed was assessed using a brief Symbol Match task (unit: second), administered on a smartphone device six times a day for 16 days and repeated annually for up to five years. Years from baseline was used as the within-person time index.
RESULTS: Results from mixed effects models showed that subjective neighborhood safety (β= -0.028) and subjective availability of healthy foods (β= -0.028) were significantly associated with less cognitive slowing over time. When objective and subjective neighborhood measures were simultaneously examined, subjective availability of healthy foods remained significant (β= -0.028) after controlling for objective availability of healthy foods. Associations of objective neighborhood crime and physical disorder with processing speed seemed to be confounded by individual-level race and socioeconomic status; after controlling for these confounders, none of objective neighborhood measures showed significant associations with processing speed.
CONCLUSIONS: Subjective neighborhood safety and subjective availability of healthy foods, rather than objective measures, were associated with less cognitive slowing over time over a five-year period. Perception of one\'s neighborhood may be a more proximal predictor of cognitive health outcomes as it may reflect one\'s experiences in the environment. It would be important to improve our understanding of both objective and subjective neighborhood factors to improve cognitive health among older adults.

Glymphatic dysfunction has been correlated with cognitive decline, with a higher choroid plexus volume (CPV) being linked to a slower glymphatic clearance rate. Nevertheless, the interplay between CPV, glymphatic function, and cognitive impairment in white matter hyperintensities (WMHs) has not yet been investigated. In this study, we performed neuropsychological assessment, T1-weighted three-dimensional (3D-T1) images, and diffusion tensor imaging (DTI) in a cohort of 206 WMHs subjects and 43 healthy controls (HCs) to further explore the relationship. The DTI analysis along the perivascular space (DTI-ALPS) index, as a measure of glymphatic function, was calculated based on DTI. Severe WMHs performed significantly worse in information processing speed (IPS) than other three groups, as well as in executive function than HCs and mild WMHs. Additionally, severe WMHs demonstrated lower DTI-ALPS index and higher CPV than HCs and mild WMHs. Moderate WMHs displayed higher CPV than HCs and mild WMHs. Mini-Mental State Examination, IPS, and executive function correlated negatively with CPV but positively with DTI-ALPS index in WMHs patients. Glymphatic function partially mediated the association between CPV and IPS, indicating a potential mechanism for WMHs-related cognitive impairment. CPV may act as a valuable prognostic marker and glymphatic system as a promising therapeutic target for WMHs-related cognitive impairment.

UNASSIGNED: The Exercise Program in Cancer and Cognition (EPICC) Study was a randomized controlled trial (RCT) designed to determine whether six months of moderate-intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET).
UNASSIGNED: Postmenopausal women with hormone receptor+, early-stage BC, within two years post-primary therapy were randomized to the exercise intervention (six months, ≥150 minutes 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.
UNASSIGNED: Participants (N=153) were 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).
UNASSIGNED: Six months of moderate-intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within two 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.

BACKGROUND: Processing Speed (PS) deficits represent a fundamental aspect of cognitive impairment, evident not only in schizophrenia but also in individuals undergoing their first episode of psychosis (FEP) and their unaffected first-degree relatives. Heterogeneity in tests assessing PS reflects the participation of motor and cognitive subcomponents to varying degrees. We aim to explore differences in performance of the subcomponents of PS in FEP patients, parents, siblings, and controls.
METHODS: Results from tests, including Trail Making Test Part A and Part B, Digit Symbol Coding Test, Grooved Pegboard Test, and Stroop Word and Stroop Color subtests, were obtained from 133 FEP patients, 146 parents, and 202 controls. Exploratory Factor Analysis (EFA) was employed in controls to establish the structure, followed by Confirmatory Factor Analysis (CFA) to verify if the other groups share this structure.
RESULTS: EFA revealed a two-factor model: Factor 1 for the motor subcomponent and Factor 2 for the cognitive subcomponent. Subsequently, CFA indicated a good fit for the remaining groups with differences in the relationship between the factors.
CONCLUSIONS: Differences in the relationships of factors within a common structure suggest the involvement of different compensatory strategies among groups, providing insights into the underlying mechanisms of PS deficits in patients and relatives.

Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm2, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.

Spoken language development after pediatric cochlear implantation requires rapid and efficient processing of novel, degraded auditory signals and linguistic information. These demands for rapid adaptation tax the information processing speed ability of children who receive cochlear implants. This study investigated the association of speed of information processing ability with spoken language outcomes after cochlear implantation in prelingually deaf children aged 4-6 years. Two domain-general (visual, non-linguistic) speed of information processing measures were administered to 21 preschool-aged children with cochlear implants and 23 normal-hearing peers. Measures of speech recognition, language (vocabulary and comprehension), nonverbal intelligence, and executive functioning skills were also obtained from each participant. Speed of information processing was positively associated with speech recognition and language skills in preschool-aged children with cochlear implants but not in normal-hearing peers. This association remained significant after controlling for hearing group, age, nonverbal intelligence, and executive functioning skills. These findings are consistent with models suggesting that domain-general, fast-efficient information processing speed underlies adaptation to speech perception and language learning following implantation. Assessment and intervention strategies targeting speed of information processing may provide better understanding and development of speech-language skills after cochlear implantation.

Children with attention-deficit/hyperactivity disorder show deficits in processing speed, as well as aberrant neural oscillations, including both periodic (oscillatory) and aperiodic (1/f-like) activity, reflecting the pattern of power across frequencies. Both components were suggested as underlying neural mechanisms of cognitive dysfunctions in attention-deficit/hyperactivity disorder. Here, we examined differences in processing speed and resting-state-Electroencephalogram neural oscillations and their associations between 6- and 12-year-old children with (n = 33) and without (n = 33) attention-deficit/hyperactivity disorder. Spectral analyses of the resting-state EEG signal using fast Fourier transform revealed increased power in fronto-central theta and beta oscillations for the attention-deficit/hyperactivity disorder group, but no differences in the theta/beta ratio. Using the parameterization method, we found a higher aperiodic exponent, which has been suggested to reflect lower neuronal excitation-inhibition, in the attention-deficit/hyperactivity disorder group. While fast Fourier transform-based theta power correlated with clinical symptoms for the attention-deficit/hyperactivity disorder group only, the aperiodic exponent was negatively correlated with processing speed across the entire sample. Finally, the aperiodic exponent was correlated with fast Fourier transform-based beta power. These results highlight the different and complementary contribution of periodic and aperiodic components of the neural spectrum as metrics for evaluation of processing speed in attention-deficit/hyperactivity disorder. Future studies should further clarify the roles of periodic and aperiodic components in additional cognitive functions and in relation to clinical status.