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The purpose of this study was to explore the internal dialogue of trainee sport psychologists (TSPs) and athletes immediately following athlete–practitioner consultations. TSPs (four male and three female, age 22–32 years) and athletes (four male, three female, age 19–29 years) completed a thought-listing procedure twice, while watching video recordings of their previous consultations. The thought-listing procedure involved participants' pausing the video to record the in-session internal dialogue they had experienced during the consultation. Participants' responses were categorized into six dimensions: time, place, focus, locus, orientation, and mode. TSPs' and athletes' retrospective accounts provided evidence that their in-session internal dialogue was (a) present focused, (b) about in-session material, (c) about the athletes or themselves, (d) about internal and external events, (e) professional (i.e., related to the session), and (f) neutral. Findings provide trainees and inexperienced practitioners with insights into the thought content of TSPs and athletes to guide their own athlete interactions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cognitive impairment is a common complaint in SLE, but approaches to measuring cognitive performance objectively vary. Leveraging data collected in a population-based cohort of individuals with validated SLE, we compared performance and potential impairment across multiple measures of cognition. METHODS: During a single study visit (October 2019-May 2022), times to complete the Trail Making Test B (TMTB; N=423) were recorded; potential impairment was defined as an age-corrected and education-corrected T-score 1.5 SD longer than the normative time). A clock drawing assessment (CLOX; N=435) with two parts (free clock draw (CLOX1) and copy (CLOX2)) was also performed (score range: 0-15; higher scores=better performance); potential impairment was defined as CLOX1 1.5 SD lower the normative score). RESULTS: Participants (mean age 46 years; 92% female; 82% black) had a median (IQR) TMTB time of 96 (76-130) s; median (IQR) CLOX1 and CLOX2 scores of 12 (10-13) and 14 (13-15); and a mean (SD) fluid cognition standard score of 87.2 (15.6). TMTB time and fluid cognition score (ρ=-0.53, p

Adolescent traumatic brain injury (TBI) has long-term effects on brain functioning and behavior, impacting neural activity under cognitive load, especially in the reward network. Adolescent TBI is also linked to risk-taking behaviors including alcohol misuse. It remains unclear how TBI and neural functioning interact to predict alcohol experimentation during adolescence. Using Adolescent Brain Cognitive Development (ABCD) study data, this project examined if TBI at ages 9-10 predicts increased odds of alcohol sipping at ages 11-13 and if this association is moderated by neural activity during the Emotional EN-Back working memory task at ages 11-13. Logistic regression analyses showed that neural activity in regions of the fronto-basal ganglia network predicted increased odds of sipping alcohol by ages 11-13 (p

Depressive symptoms may either be a risk factor or prodromal to dementia. Investigating this association in midlife may help clarify the role of depression in cognitive aging. We aimed to identify trajectories in depressive symptoms in early to mid-life and related cognitive and brain outcomes in midlife. This study includes 3944 Black and White participants (ages 26-45 years at baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with 20 years of follow-up. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale at five time points over 20 years. Growth mixture modeling (GMM) was used to identify depressive symptom trajectories. Participants completed a neuropsychological battery 20 years after baseline, including the Digit Symbol Substitution Test (DSST), Rey-Auditory Verbal Learning Test (RAVLT), Stroop Test, Montreal Cognitive Assessment (MoCA), and category and letter fluency tests. A sub-sample of participants (n = 662) underwent brain magnetic resonance imaging (MRI) to characterize gray matter volumes and white matter hyperintensities (WMHs). We identified four classes of depressive symptom trajectories: a declining class (n = 286, 7.3%) with initially high symptoms and subsequent decline, a class with consistently high symptoms (steady high; n = 264, 6.7%), a class with late increases in symptoms (increasing; n = 277, 7%), and a class with consistently low symptoms (steady low; n = 3117, 79.0%). The steady high and the increasing classes had poorer performance on all cognitive tests, while the declining class had poorer performance on the DSST, verbal fluency, and MoCA. Compared to the steady low symptom class, the steady high class had lower volumes in the entorhinal cortex (β: -180.80, 95% CI: -336.69 to -24.91) and the amygdala (β: -40.97, 95% CI: -74.09 to -7.85), the increasing class had more WMHs (β: 0.55, 95% CI: 0.22 to 0.89), and the declining class was not significantly different in any brain measures. Trajectories in depressive symptoms in young to mid-adulthood show distinct cognitive and brain phenotypes in midlife. Steady high depressive symptoms may represent a group that is at risk for dementia, whereas increasing symptoms in midlife may be associated with white matter damage.

BACKGROUND: In healthy people, the fight-or-flight sympathetic system is counterbalanced by the rest-and-digest parasympathetic system. As we grow older, the parasympathetic system declines as the sympathetic system becomes hyperactive. In our prior heart rate variability biofeedback and emotion regulation (HRV-ER) clinical trial, we found that increasing parasympathetic activity through daily practice of slow-paced breathing significantly decreased plasma amyloid-β (Aβ) in healthy younger and older adults. In healthy adults, higher plasma Aβ is associated with greater risk of Alzheimers disease (AD). Our primary goal of this trial is to reproduce and extend our initial findings regarding effects of slow-paced breathing on Aβ. Our secondary objectives are to examine the effects of daily slow-paced breathing on brain structure and the rate of learning. METHODS: Adults aged 50-70 have been randomized to practice one of two breathing protocols twice daily for 9 weeks: (1) slow-paced breathing condition involving daily cognitive training followed by slow-paced breathing designed to maximize heart rate oscillations or (2) random-paced breathing condition involving daily cognitive training followed by random-paced breathing to avoid increasing heart rate oscillations. The primary outcomes are plasma Aβ40 and Aβ42 levels and plasma Aβ42/40 ratio. The secondary outcomes are brain perivascular space volume, hippocampal volume, and learning rates measured by cognitive training performance. Other pre-registered outcomes include plasma pTau-181/tTau ratio and urine Aβ42. Recruitment began in January 2023. Interventions are ongoing and will be completed by the end of 2023. DISCUSSION: Our HRV-ER trial was groundbreaking in demonstrating that a behavioral intervention can reduce plasma Aβ levels relative to a randomized control group. We aim to reproduce these findings while testing effects on brain clearance pathways and cognition. TRIAL REGISTRATION: ClinicalTrials.gov NCT05602220. Registered on January 12, 2023.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists throughout the world with over 65 million registered cases of survivors with post-COVID-19 sequelae, also known as LongCOVID-19 (LongC). LongC survivors exhibit various symptoms that span multiple organ systems, including the nervous system. To search for neurological markers of LongC, we investigated the soluble biomolecules present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected between 2020 and 2022, not hospitalized, and were vaccinated or unvaccinated before infection. IL-1β was significantly increased in both nLongC and Cov and IL-8 was elevated in only nLongC. Both brain-derived neurotrophic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and TDP-43. This study shows chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms.

IntroductionReproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women.MethodsParticipants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence).ResultsYounger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence.DiscussionSeveral aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

IntroductionAbnormal amyloid-beta (Aβ) and tau deposition define Alzheimer's Disease (AD), but non-elevated tau is relatively frequent in patients on the AD pathway.MethodsWe examined characteristics and regional patterns of 397 Aβ+ unimpaired and impaired individuals with low tau (A+T-) in relation to their higher tau counterparts (A+T+).ResultsSeventy-one percent of Aβ+ unimpaired and 42% of impaired Aβ+ individuals were categorized as A+T- based on global tau. In impaired individuals only, A+T- status was associated with older age, male sex, and greater cardiovascular risk. α-synuclein was linked to poorer cognition, particularly when tau was low. Tau burden was most frequently elevated in a common set of temporal regions regardless of T+/T- status.DiscussionLow tau is relatively common in patients on the AD pathway and is linked to comorbidities that contribute to impairment. These findings have implications for the selection of individuals for Aβ- and tau-modifying therapies.

IntroductionWith emergence of disease-modifying therapies, efficient diagnostic pathways are critically needed to identify treatment candidates, evaluate disease severity, and support prognosis. A combination of plasma biomarkers and brief digital cognitive assessments could provide a scalable alternative to current diagnostic work-up.MethodsWe examined the accuracy of plasma biomarkers and a 10-minute supervised tablet-based cognitive assessment (Tablet-based Cognitive Assessment Tool Brain Health Assessment [TabCAT-BHA]) in predicting amyloid β positive (Aβ+) status on positron emission tomography (PET), concurrent disease severity, and functional decline in 309 older adults with subjective cognitive impairment (n = 49), mild cognitive impairment (n = 159), and dementia (n = 101).ResultsCombination of plasma pTau181, Aβ42/40, neurofilament light (NfL), and TabCAT-BHA was optimal for predicting Aβ-PET positivity (AUC = 0.962). Whereas NfL and TabCAT-BHA optimally predicted concurrent disease severity, combining these with pTau181 and glial fibrillary acidic protein was most accurate in predicting functional decline.DiscussionCombinations of plasma and digital cognitive markers show promise for scalable diagnosis and prognosis of ADRD.HighlightsThe need for cost-efficient diagnostic and prognostic markers of AD is urgent. Plasma and digital cognitive markers provide complementary diagnostic contributions. Combination of these markers holds promise for scalable diagnosis and prognosis. Future validation in community cohorts is needed to inform clinical implementation.

Focal epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood. We used fluorescent glutamate and GABA sensors in an awake rodent model of neocortical seizures to resolve the spatiotemporal evolution of both neurotransmitters in the extracellular space. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagated centrifugally. GABA transients lasted longer than glutamate transients and were maximal ∼1.5 mm from the focus where they propagated centripetally. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing seizures to escape from local inhibitory restraint.

Humans regularly solve complex problems in cooperative teams. A wide range of mechanisms have been identified that improve the quality of solutions achieved by those teams on reaching consensus. We argue that many of these mechanisms work via increasing the transient diversity of solutions while the group attempts to reach a consensus. These mechanisms can operate at the level of individual psychology (e.g., behavioral inertia), interpersonal communication (e.g., transmission noise), or group structure (e.g., sparse social networks). Transient diversity can be increased by widening the search space of possible solutions or by slowing the diffusion of information and delaying consensus. All of these mechanisms increase the quality of the solution at the cost of increased time to reach it. We review specific mechanisms that facilitate transient diversity and synthesize evidence from both empirical studies and diverse formal models-including multiarmed bandits, NK landscapes, cumulative-innovation models, and evolutionary-transmission models. Apparent exceptions to this principle occur primarily when problems are sufficiently simple that they can be solved by mere trial and error or when the incentives of team members are insufficiently aligned. This work has implications for our understanding of collective intelligence, problem solving, innovation, and cumulative cultural evolution.

ObjectivePhysical and recreational activities are behaviors that may modify risk of late-life cognitive decline. We sought to examine the role of retrospectively self-reported midlife (age 40) physical and recreational activity engagement - and self-reported change in these activities from age 40 to initial study visit - in predicting late-life cognition.MethodData were obtained from 898 participants in a longitudinal study of cognitive aging in demographically and cognitively diverse older adults (Age: range = 49-93 years, M = 75, SD = 7.19). Self-reported physical and recreational activity participation at age 40 and at the initial study visit were quantified using the Life Experiences Assessment Form. Change in activities was modeled using latent change scores. Cognitive outcomes were obtained annually (range = 2-17 years) using the Spanish and English Neuropsychological Assessment Scales, which measure verbal episodic memory, semantic memory, visuospatial processing, and executive functioning.ResultsPhysical activity engagement at age 40 was strongly associated with cognitive performance in all four domains at the initial visit and with global cognitive slope. However, change in physical activities after age 40 was not associated with cognitive outcomes. In contrast, recreational activity engagement - both at age 40 and change after 40 - was predictive of cognitive intercepts and slope.ConclusionsRetrospectively self-reported midlife physical and recreational activity engagement were strongly associated with late-life cognition - both level of performance and rate of future decline. However, the data suggest that maintenance of recreational activity engagement (e.g., writing, taking classes, reading) after age 40 is more strongly associated with late-life cognition than continued maintenance of physical activity levels.

Context: A healthy, 22-year-old, male NCAA Division I baseball shortstop was experiencing confusion, chest pain, and tightness during an off-season intersquad scrimmage. The patient did not have any significant medical history or mechanism of head injury. After initial evaluation from the athletic trainer, the patient's cognitive status began to quickly decline. The emergency action plan was put in place rapidly and referred the patient to the local emergency clinic. Case Presentation: Upon arrival at the emergency department, an electrocardiogram was performed to rule out myocardial infarction or stroke. The first electrocardiogram results returned negative for any cardiac pathology, but a stroke alert was called. The patient was then transported to a level II trauma center due to continual cognitive decline. The patient was diagnosed with transient ischemic attack (TIA) secondary to an undiagnosed patent foramen ovale (PFO) that would later be diagnosed with further evaluation 2 months after the initial TIA incident. After multiple diagnostic and laboratory tests, the PFO went undetected until a 2D echocardiogram was performed and evaluated by a cardiologist. Management and Outcomes: After the confirmation of the congenital defect, surgical intervention was performed to correct the PFO using catheterization. Despite multiple preparticipation examinations, electrocardiograms, and examination of past family history, the PFO went undetected until the patient experienced symptoms of TIA. The discovery of PFO in this 22-year-old athletic individual is unusual because traditional screening techniques (electrocardiogram and preparticipation examinations) failed to detect the congenital defect. Conclusions: Due to the emergent and timely actions of the athletic trainer, the patient has made a full recovery and is able to compete fully in athletic events. This case study amplifies the need for athletic trainers at all sporting events, updated and reviewed emergency action plans, rapid recognition of TIA in athletic individuals, and return-to-play protocol for an athletic individual after TIA. [ABSTRACT FROM AUTHOR]

In terms of utility and technical quality, open-source software solutions have become a common option for many libraries. As barriers to adoption have been reduced and systems such as FOLIO appear poised to change the landscape of LIS technology, it is worth examining how the use of open source can support the normative core values of librarianship and to outline a strategy for critical engagement with the technology that is beneficial to patrons and libraries. Such a strategy will require further codification, institutionalization, and investigation of open source at many levels. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) rupture can impair balance performance, particularly during cognitive motor dual-tasks, This study aimed to determine the effects of various modalities of cognitive load (working memory, and visuospatial and executive function) on postural control parameters in individuals with ACL injury. Twenty-seven ACL-injured and 27 healthy participants were evaluated doing different cognitive tasks (silent backward counting. Benton's judgment of line orientation. and Stroop color-word test) while standing on a rigid surface or a foam. Each task was repeated three times and then averaged. Center of pressure variables used to measure postural performance included sway area and sway velocity in anterior-posterior and medial-lateral directions, Cognitive performance was also assessed by calculating errors and the score of cognitive tasks. A mixed model analysis of variance for center of pressure parameters indicated that patients had more sways than the healthy group. The interaction of group by postural difficulty by cognitive tasks was statistically significant for cognitive errors (p < .01), and patients with ACL injury indicated more cognitive errors compared to healthy controls while standing on the foam. The main effect of cognitive task was statistically significant for all postural parameters, representing reduced postural sways in both groups with all cognitive tasks. However, ACL-injured patients showed more cognitive errors in difficult postural conditions, suggesting that individuals with ACL injury may prioritize postural control over cognitive task accuracy and adopt the posture-first strategy to maintain balance under dual-task conditions. [ABSTRACT FROM AUTHOR]

Disruptions in gait function are common after concussion in adolescents; however, the neuromotor control deficits driving these gait disruptions are not well known. Fifteen concussed (age mean [SD]): 17.4 [0.6], 13 females, days since injury: 26.3 [9.9]) and 17 uninjured (age: 18.0 [0.7], 10 females) adolescents completed 3 trials each of single-task gait and dual-task gait (DT). During DT, participants simultaneously walked while completing a serial subtraction task. Gait metrics and variability in instantaneous mean frequency in lower extremity muscles were captured by inertial sensors and surface electromyography, respectively. A 2-way analysis of covariance was used to compare gait metrics across groups and conditions. Functional principal components analysis was used to identify regions of variability in instantaneous mean frequency curves. Functional principal component scores were compared across groups using a Welch statistic. Both groups displayed worse performance on gait metrics during DT condition compared to single-task, with no differences between groups (P <.001). Concussed adolescents displayed significantly greater instantaneous mean frequency, indicated by functional principal component 1, in the tibialis anterior, biceps femoris, and semitendinosus (P <.05) during single-task and DT compared with uninjured adolescents. Our observations suggest that concussed adolescents display inefficient motor unit recruitment lasting longer than 2 weeks following injury, regardless of the addition of a secondary task. [ABSTRACT FROM AUTHOR]

Through an ethnographic study of decision making in a rape crisis center, I explore how institutional logics come to be through interactions. Zooming in on storytelling interactions and slowing down to follow their evolution, I find that collective cognitive, political, and emotional elements mediated the narration of logics into effect. While the interactions unfolded within a space of possibilities determined by logics, co-narrators still put much cognitive effort into negotiating which logic was relevant and how it implicated specific ways of understanding and responding to events. Narrators' subject positions and their perceived interests and emotions also mediated the work of logics on the ground. Decisions were determined by degrees of coherence across these cognitive, political, and emotional elements. When there was high or moderate coherence, the decision followed the resolution implied by the narration. When coherence was low, decision makers rejected the decision implied by the narration. Coherence, then, constrained people's agency to invoke institutional logic. These results offer compelling new theory about how institutional logics work: logics are neither deterministic nor freely manipulated but instantiated through collective and situated dynamics that set limits on their strategic use. [ABSTRACT FROM AUTHOR]

Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) accompanied by cerebrovascular risk factors (CVRFs) are known to increase the risk of developing dementia. Mind-body practices such as yoga and meditation, have been recognized as safe techniques with beneficial effects on cognitive functions in older adults at risk for cognitive decline. We conducted a randomized, controlled trial to assess the efficacy of Kundalini yoga training (KY) compared to memory enhancement training (MET) on mood and cognitive functioning in a group of older women with CVRFs and SCD (clinicaltrials.gov = NCT03503669). The KY intervention consisted of weekly, 60-min in-person classes with a certified instructor for 12 weeks, with a 12-min guided recording for daily homework practice at home. MET involved 12 weekly in-person group classes with 12-min daily homework exercises. Objective and subjective memory performance were the primary outcomes. Peripheral whole blood samples were collected at baseline, 12-weeks, and 24-weeks follow-up for RNA sequencing and cytokine/chemokine assays. A total of 79 patients (KY = 40; MET = 39) were randomized, and 63 completed the 24-week follow-up (KY = 65% completion rate; MET = 95%; χ2(1) = 10.9, p

Joking draws on complex cognitive abilities: understanding social norms, theory of mind, anticipating others responses and appreciating the violation of others expectations. Playful teasing, which is present in preverbal infants, shares many of these cognitive features. There is some evidence that great apes can tease in structurally similar ways, but no systematic study exists. We developed a coding system to identify playful teasing and applied it to video of zoo-housed great apes. All four species engaged in intentionally provocative behaviour, frequently accompanied by characteristics of play. We found playful teasing to be characterized by attention-getting, one-sidedness, response looking, repetition and elaboration/escalation. It takes place mainly in relaxed contexts, has a wide variety of forms, and differs from play in several ways (e.g. asymmetry, low rates of play signals like the playface and absence of movement-final holds characteristic of intentional gestures). As playful teasing is present in all extant great ape genera, it is likely that the cognitive prerequisites for joking evolved in the hominoid lineage at least 13 million years ago.

BACKGROUND: Few adolescents meet guideline levels of physical activity associated with good health, highlighting the need for intervention. Interventions promoting adolescents physical activity should be guided by research applying behavioral theory to identify potentially modifiable correlates and associated processes. We applied an integrated social cognition model to identify theory-based constructs and processes that relate to physical activity intentions in a secondary analysis of two samples of Finnish adolescents using a correlational design. METHOD: Participants in the first sample (n = 455) completed self-report measures of social cognition constructs from theory of planned behavior, habit, self-discipline, and past and current physical activities. Participants in the second sample (n = 3878) completed identical measures plus measures of socio-structural and socio-environmental factors. Participants from the first sample also wore accelerometers for 1 week. Hypothesized model effects were tested using variance-based structural equation modeling in data from the first sample and subsequently confirmed in a pre-registered analysis of data from the second sample. RESULTS: Across both samples, habit, attitude, perceived behavioral control, and self-reported past behavior were associated with physical activity intention. Effects of self-reported past physical activity on intention were partially mediated by social cognition constructs. Effects of accelerometer-based physical activity were small by comparison. Effects of socio-structural and socio-environmental factors on intention in the second sample were partially mediated by the social cognition constructs. CONCLUSION: Results corroborate beliefs and habit as consistent correlates of adolescents physical activity intentions and provide preliminary evidence that social cognition constructs account for effects of socio-structural and socio-environmental factors on intentions.

BackgroundLoneliness is more common in older adults and those who face structural vulnerabilities, including homelessness. The homeless population is aging in the United States; now, 48% of single homeless adults are 50 and older. We know little about loneliness among older adults who have experienced homelessness. We aimed to describe the loneliness experience among homeless-experienced older adults with cognitive and functional impairments and the individual, social, and structural conditions that shaped these loneliness experiences.MethodsWe purposively sampled 22 older adults from the HOPE HOME study, a longitudinal cohort study among adults aged 50 years or older experiencing homelessness in Oakland, California. We conducted in-depth interviews about participants perceived social support and social isolation. We conducted qualitative content analysis.ResultsTwenty participants discussed loneliness experience, who had a median age of 57 and were mostly Black (80%) and men (65%). We developed a typology of participants' loneliness experience and explored the individual, social, and structural conditions under which each loneliness experience occurred. We categorized the loneliness experience into four groups: (1) "lonely- distressed", characterized by physical impairment and severe isolation; (2) "lonely- rather be isolated", reflecting deliberate social isolation as a result of trauma, marginalization and aging-related resignation; (3) "lonely- transient", as a result of aging, acceptance and grieving; and (4) "not lonely"- characterized by stability and connection despite having experienced homelessness.ConclusionsLoneliness is a complex and heterogenous social phenomenon, with homeless-experienced older adults with cognitive or functional impairments exhibiting diverse loneliness experiences based on their individual life circumstances and needs. While the most distressing loneliness experience occurred among those with physical impairment and mobility challenges, social and structural factors such as interpersonal and structural violence during homelessness shaped these experiences.

Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinsons disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown. This study examined the relationship of white matter and basal ganglia PVS with domain-specific and global cognition in individuals with PD. Fifty individuals with PD underwent 3T T1w magnetic resonance imaging (MRI) to determine PVS volume fraction, defined as PVS volume normalized to total regional volume, within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of global cognitive function (Montreal Cognitive Assessment, and global cognitive composite score), and cognitive-specific domains (executive function, memory, visuospatial function, attention, and language). Higher white matter rostral middle frontal PVS was associated with lower scores in both global cognitive and visuospatial function. In the basal ganglia higher PVS was associated with lower scores for memory with a trend towards lower global cognitive composite score. While previous reports have shown that greater amount of PVS in the basal ganglia is associated with decline in global cognition in PD, our findings suggest that increased white matter PVS volume may also underlie changes in cognition.

IntroductionThe Last Gift study at the University of California San Diego (UCSD), United States enrolls terminally ill people with HIV (PWH) in HIV cure research.MethodsFrom 2017 to 2022, we conducted surveys with Last Gift participants and their next-of-kin/loved ones to evaluate willingness to participate in different types of HIV cure research at the end of life (EOL). We analyzed willingness data descriptively.ResultsWe surveyed 17 Last Gift participants and 17 next-of-kin/loved ones. More than half of Last Gift participants ( n  = 10; 58.8%) expressed willingness to participate in studies involving totally new treatments or approaches ('first-in-human' studies), a combination of different approaches, the use of unique antibodies, proteins or molecules, or therapeutic vaccines. Under one-quarter of Last Gift participants ( n  = 4; 23.5%) expressed willingness to participate in research involving interventions that may shorten their life expectancy to benefit medical research. Most Last Gift participants and their next-of-kin/loved ones also expressed high acceptance for various types of donations and biopsies at the EOL (e.g. hair donations and skin, lymph node or gut biopsies).DiscussionKnowing whether people would be willing to participate in different types of EOL HIV cure research can help inform the design of future innovative studies. As a research community, we have a duty to design studies with adequate safeguards to preserve the public trust in research and honor PWH's important gift to humanity.

Cross-sectional studies have linked differences in white matter tissue properties to reading skills. However, past studies have reported a range of, sometimes conflicting, results. Some studies suggest that white matter properties act as individual-level traits predictive of reading skill, whereas others suggest that reading skill and white matter develop as a function of an individual's educational experience. In the present study, we tested two hypotheses: a) that diffusion properties of the white matter reflect stable brain characteristics that relate to stable individual differences in reading ability or b) that white matter is a dynamic system, linked with learning over time. To answer these questions, we examined the relationship between white matter and reading in a five-year longitudinal dataset and a series of large-scale, single-observation, cross-sectional datasets (N = 14,249 total participants). We find that gains in reading skill correspond to longitudinal changes in the white matter. However, in the cross-sectional datasets, we find no evidence for the hypothesis that individual differences in white matter predict reading skill. These findings highlight the link between dynamic processes in the white matter and learning.

Functional neuroimaging emerged with great promise and has provided fundamental insights into the neurobiology of schizophrenia. However, it has faced challenges and criticisms, most notably a lack of clinical translation. This paper provides a comprehensive review and critical summary of the literature on functional neuroimaging, in particular functional magnetic resonance imaging (fMRI), in schizophrenia. We begin by reviewing research on fMRI biomarkers in schizophrenia and the clinical high risk phase through a historical lens, moving from case-control regional brain activation to global connectivity and advanced analytical approaches, and more recent machine learning algorithms to identify predictive neuroimaging features. Findings from fMRI studies of negative symptoms as well as of neurocognitive and social cognitive deficits are then reviewed. Functional neural markers of these symptoms and deficits may represent promising treatment targets in schizophrenia. Next, we summarize fMRI research related to antipsychotic medication, psychotherapy and psychosocial interventions, and neurostimulation, including treatment response and resistance, therapeutic mechanisms, and treatment targeting. We also review the utility of fMRI and data-driven approaches to dissect the heterogeneity of schizophrenia, moving beyond case-control comparisons, as well as methodological considerations and advances, including consortia and precision fMRI. Lastly, limitations and future directions of research in the field are discussed. Our comprehensive review suggests that, in order for fMRI to be clinically useful in the care of patients with schizophrenia, research should address potentially actionable clinical decisions that are routine in schizophrenia treatment, such as which antipsychotic should be prescribed or whether a given patient is likely to have persistent functional impairment. The potential clinical utility of fMRI is influenced by and must be weighed against cost and accessibility factors. Future evaluations of the utility of fMRI in prognostic and treatment response studies may consider including a health economics analysis.

Transcription-coupled nucleotide excision repair (TC-NER) is a highly conserved DNA repair pathway that removes bulky lesions in the transcribed genome. Cockayne syndrome B protein (CSB), or its yeast ortholog Rad26, has been known for decades to play important roles in the lesion-recognition steps of TC-NER. Another conserved protein ELOF1, or its yeast ortholog Elf1, was recently identified as a core transcription-coupled repair factor. How Rad26 distinguishes between RNA polymerase II (Pol II) stalled at a DNA lesion or other obstacles and what role Elf1 plays in this process remains unknown. Here, we present cryo-EM structures of Pol II-Rad26 complexes stalled at different obstacles that show that Rad26 uses a common mechanism to recognize a stalled Pol II, with additional interactions when Pol II is arrested at a lesion. A cryo-EM structure of lesion-arrested Pol II-Rad26 bound to Elf1 revealed that Elf1 induces further interactions between Rad26 and a lesion-arrested Pol II. Biochemical and genetic data support the importance of the interplay between Elf1 and Rad26 in TC-NER initiation. Together, our results provide important mechanistic insights into how two conserved transcription-coupled repair factors, Rad26/CSB and Elf1/ELOF1, work together at the initial lesion recognition steps of transcription-coupled repair.

BACKGROUND: APOE4 is the strongest genetic risk factor for sporadic Alzheimers disease (AD), whereas APOE2 confers protection. However, effects of APOE on neurodegeneration in cognitively intact individuals, and how these associations evolve with cognitive decline, are unclear. Furthermore, few studies have evaluated whether effects of APOE on neurodegenerative changes are modified by other AD key risk factors including age and sex. METHODS: Participants included older adults (57% women; 77 ± 7 years) from the Rancho Bernardo Study of Health Aging and the University of California San Diego Alzheimers Disease Research Center, including 192 cognitively normal (CN) individuals and 33 with mild cognitive impairment. Participants underwent diffusion MRI, and multicompartment restriction spectrum imaging (RSI) metrics were computed in white matter, gray matter, and subcortical regions of interest. Participants were classified as APOE4 carriers, APOE2 carriers, and APOE3 homozygotes. Analysis of covariance among CN (adjusting for age, sex, and scanner) assessed differences in brain microstructure by APOE, as well as interactions between APOE and sex. Analyses across all participants examined interactions between APOE4 and cognitive status. Linear regressions assessed APOE by age interactions. RESULTS: Among CN, APOE4 carriers showed lower entorhinal cortex neurite density than non-carriers, whereas APOE2 carriers showed lower cingulum neurite density than non-carriers. Differences in entorhinal microstructure by APOE4 and in entorhinal and cingulum microstructure by APOE2 were present for women only. Age correlated with lower entorhinal restricted isotropic diffusion among APOE4 non-carriers, whereas age correlated with lower putamen restricted isotropic diffusion among APOE4 carriers. Differences in microstructure between cognitively normal and impaired participants were stronger for APOE4-carriers in medial temporal regions, thalamus, and global gray matter, but stronger for non-carriers in caudate. CONCLUSIONS: The entorhinal cortex may be an early target of neurodegenerative changes associated with APOE4 in presymptomatic individuals, whereas APOE2 may support beneficial white matter and entorhinal microstructure, with potential sex differences that warrant further investigation. APOE modifies microstructural patterns associated with aging and cognitive impairment, which may advance the development of biomarkers to distinguish microstructural changes characteristic of normal brain aging, APOE-dependent pathways, and non-AD etiologies.

BackgroundAlzheimer's disease (AD) is the most common form of dementia, progressively impairing cognitive abilities. While neuroimaging studies have revealed functional abnormalities in AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. Using magnetoencephalography imaging we documented abnormal local neural synchrony patterns in patients with AD. To identify global abnormal biophysical mechanisms underlying the spatial and spectral electrophysiological patterns in AD, we estimated the parameters of a biophysical spectral graph model (SGM).MethodsSGM is an analytic neural mass model that describes how long-range fiber projections in the brain mediate the excitatory and inhibitory activity of local neuronal subpopulations. Unlike other coupled neuronal mass models, the SGM is linear, available in closed-form, and parameterized by a small set of biophysical interpretable global parameters. This facilitates their rapid and unambiguous inference which we performed here on a well-characterized clinical population of patients with AD (N = 88, age = 62.73 +/- 8.64 years) and a cohort of age-matched controls (N = 88, age = 65.07 +/- 9.92 years).ResultsPatients with AD showed significantly elevated long-range excitatory neuronal time scales, local excitatory neuronal time scales and local inhibitory neural synaptic strength. The long-range excitatory time scale had a larger effect size, compared to local excitatory time scale and inhibitory synaptic strength and contributed highest for the accurate classification of patients with AD from controls. Furthermore, increased long-range time scale was associated with greater deficits in global cognition.ConclusionsThese results demonstrate that long-range excitatory time scale of neuronal activity, despite being a global measure, is a key determinant in the local spectral signatures and cognition in the human brain, and how it might be a parsimonious factor underlying altered neuronal activity in AD. Our findings provide new insights into mechanistic links between abnormal local spectral signatures and global connectivity measures in AD.

Abstract: Background: Fatigue and neurocognitive impairment are highly prevalent in patients with glioma, significantly impacting health-related quality of life. Despite the presumed association between these two factors, evidence remains sparse. Therefore, we aimed to investigate this relationship using multinational data. Methods: We analyzed data on self-reported fatigue and neurocognitive outcomes from postoperative patients with glioma from the University of California San Francisco (n = 100, UCSF) and Amsterdam University Medical Center (n = 127, Amsterdam UMC). We used multiple linear regression models to assess associations between fatigue and seven (sub)domains of neurocognitive functioning and latent profile analysis to identify distinct patterns of fatigue and neurocognitive functioning. Results: UCSF patients were older (median age 49 vs. 43 years, P = .002), had a higher proportion of grade 4 tumors (32% vs. 18%, P = .03), and had more neurocognitive deficits (P = .01). While the number of clinically fatigued patients was similar between sites (64% vs. 58%, P = .12), fatigue and the number of impaired neurocognitive domains were not correlated (P = .16–.72). At UCSF, neurocognitive domains were not related to fatigue, and at Amsterdam UMC attention and semantic fluency explained only 4–7% of variance in fatigue. Across institutions, we identified four distinct patterns of neurocognitive functioning, which were not consistently associated with fatigue. Conclusions: Although individual patients might experience both fatigue and neurocognitive impairment, the relationship between the two is weak. Consequently, both fatigue and neurocognitive functioning should be independently assessed and treated with targeted therapies.

ObjectiveSubjective cognitive decline (SCD) is a potential early risk marker for Alzheimer's disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status.MethodsFifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk).ResultsHigher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only.ConclusionsOur preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline.

ObjectiveMethamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.Method423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M-/M+) and/or cannabis (C-/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.ResultsGlobally, M+C+ performed worse than M-C- but better than M+C-. M+C+ outperformed M+C- on measures of verbal fluency, information processing speed, learning, memory, and working memory. M-C+ did not display lower performance than M-C- globally or on any domain measures, and M-C+ even performed better than M-C- on measures of learning, memory, and working memory.ConclusionsOur findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.

Abstract: In this essay, we approach the question of what it means for something to be symbolic in a different way from the usual answers rooted in philosophy, sociology or anthropology: we argue that the symbolic is, first and foremost, rooted in human biology and human evolution. We discuss how the development of the capability to create and share symbols was a key moment in human evolution that underpins our capability to communicate and store knowledge through language, to think abstractly about problems, and to live and work together effectively in large groups. It also underpins the unique ecological niche – the cognitive niche – that Homo sapiens construct using our capability to create and share symbols. We go on to explore some of the implications of an evolutionary understanding of the symbolic for management and organization research.

In the United States, college students experience disproportionate food insecurity (FI) rates compared to the national prevalence. The experience of acute and chronic FI has been associated with negative physical and mental health outcomes in this population. This narrative review aims to summarize the current methodologies for assessing health outcomes associated with the experience of FI in college students in the United States. To date, assessing the health outcomes of FI has predominately consisted of subjective assessments, such as self-reported measures of dietary intake, perceived health status, stress, depression, anxiety, and sleep behaviors. This review, along with the emergence of FI as an international public health concern, establishes the need for novel, innovative, and objective biomarkers to evaluate the short- and long-term impacts of FI on physical and mental health outcomes in college students. The inclusion of objective biomarkers will further elucidate the relationship between FI and a multitude of health outcomes to better inform strategies for reducing the pervasiveness of FI in the United States college student population.

This study explores sex-differences in (a) rates and profiles of autism symptoms as well as in (b) the contribution of intellectual quotient (IQ) to autism symptom presentation in Down syndrome (DS). Participants were 40 males and 38 females with DS, aged 6 to 23 years. Autism symptoms were rated through the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). Results show no sex differences in the ADOS-2 Calibrated Severity Scores (CSS). However, only females with DS who are classified as DS-Only have higher scores on verbal IQ than those classified as DS + autism. Furthermore, associations between IQ and all CSSs are found for females, but not for males. Findings suggest that verbal cognition may play differential roles for females and males with DS.

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and children born preterm or with low birthweight showed catch-up growth with age. Socioeconomic factors exerted region- and time-specific effects. Regarding cognition, males scored lower than females; preterm birth affected all developmental areas tested, and socioeconomic factors affected visual reception and receptive language. Brain-cognition correlations revealed region-specific associations.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by challenges in social interaction and communication and the presence of restricted interests and repetitive behaviors. The importance of early detection of ASD and subsequent early intervention is well documented. Efforts have been made over the years to clarify ASD diagnostic criteria and develop predictive, accurate screening tools and evidence-based, standardized diagnostic instruments to aid in the identification of ASD. In this article, we review the most recent changes in ASD diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision, summarize evidence-based instruments for ASD screening and diagnostic evaluations as well as the assessment of co-occurring conditions in ASD, the impact of COVID-19 on ASD assessment, and directions for future research in the field of ASD assessment.

ObjectiveNegative life events (NLEs), e.g., poor academic performance (controllable) or being the victim of a crime (uncontrollable), can profoundly affect the trajectory of one's life. Yet, their impact on how the brain develops is still not well understood. This investigation examined the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) dataset for the impact of NLEs on the initiation of alcohol and cannabis use, as well as underlying neural mechanisms.MethodsThis study evaluated the impact of controllable and uncontrollable NLEs on substance use initiation in 207 youth who initiated alcohol use, 168 who initiated cannabis use, and compared it to 128 youth who remained substance-naïve, using generalised linear regression models. Mediation analyses were conducted to determine neural pathways of NLE impacting substance use trajectories.ResultsDose-response relationships between controllable NLEs and substance use initiation were observed. Having one controllable NLE increased the odds of alcohol initiation by 50% (95%CI [1.18, 1.93]) and cannabis initiation by 73% (95%CI [1.36, 2.24]), respectively. Greater cortical thickness in left banks of the superior temporal sulcus mediated effects of controllable NLEs on alcohol and cannabis initiations. Greater left caudate gray-matter volumes mediated effects of controllable NLEs on cannabis initiation.ConclusionsControllable but not uncontrollable NLEs increased the odds of alcohol and cannabis initiation. Moreover, those individuals with less mature brain structures at the time of the NLEs experienced a greater impact of NLEs on subsequent initiation of alcohol or cannabis use. Targeting youth experiencing controllable NLEs may help mitigate alcohol and cannabis initiation.

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimers disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (β = 0.88, 95% CI = 0.45; 1.38, p

OBJECTIVES: Alzheimers disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden. METHODS: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities. RESULTS: In A+ category, compared with the frequency of Alzheimers pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p

This study aimed to determine the association between severity of autism spectrum disorder (ASD) and cognitive, behavioral, and molecular measures in individuals with fragile X syndrome (FXS). Study inclusion criteria included individuals with FXS and (1) age 6-40 years, (2) full-scale IQ

PURPOSE: Patients with cancer often experience elevated levels of distress. This double-blind, randomized controlled trial compared the impact of an app-based version of cognitive behavioral stress management (CBSM) versus a health education sham app on anxiety and depression symptoms. METHODS: Patients with nonmetastatic (stage I-III) cancer who were receiving or recently completed (≤6 months) systemic treatment were recruited nationwide. The primary outcome of change in anxiety symptoms (PROMIS-Anxiety) over 12 weeks and the top secondary outcome of change in depression symptoms (PROMIS-Depression) over 12 weeks were analyzed using mixed-effects modeling with repeated measures (weeks 0, 4, 8, 12). Patient global impressions of change in anxiety and depression were reported at weeks 4, 8, and 12. In addition, self-reported adverse events were collected throughout the study and adjudicated by the site principal investigator. RESULTS: Four hundred forty-nine patients were enrolled in the trial (age M [standard deviation] = 52.44 [11.46]; 81% female; 76% White; 53% breast cancer). Patients randomly assigned to digitized CBSM showed significantly greater reductions in anxiety (B = -0.03; P = .019) and depression (B = -0.02; P = .042) symptoms over 12 weeks. Patients who received digitized CBSM were also significantly more likely to perceive much or very much improvement (v no/minimal change or much/very much worse) in their symptoms of anxiety (χ2 = 31.76; P < .001) and depression (χ2 = 19.70; P < .001) compared with the control. CONCLUSION: The use of digitized CBSM led to significant improvements in anxiety and depression outcomes compared with the sham app.

BackgroundHIV-associated neurocognitive disorders (HANDs) remain prevalent despite antiretroviral therapy, particularly among older people with HIV (PWH). However, the diagnosis of HAND is labor intensive and requires expertise to administer neuropsychological tests. Our prior pilot work established the feasibility and accuracy of a computerized self-administered virtual reality program (DETECT; Display Enhanced Testing for Cognitive Impairment and Traumatic Brain Injury) to measure cognition in younger PWH. The present study expands this to a larger sample of older PWH.MethodsWe enrolled PWH who were ≥60 years old, were undergoing antiretroviral therapy, had undetectable plasma viral loads, and were without significant neuropsychological confounds. HAND status was determined via Frascati criteria. Regression models that controlled for demographic differences (age, sex, education, race/ethnicity) examined the association between DETECT's cognition module and both HAND status and Global Deficit Score (GDS) derived via traditional neuropsychological tests.ResultsSeventy-nine PWH (mean age, 66 years; 28% women) completed a comprehensive neuropsychological battery and DETECT's cognition module. Twenty-five (32%) had HAND based on the comprehensive battery. A significant correlation was found between the DETECT cognition module and the neuropsychological battery (r = 0.45, P < .001). Furthermore, in two separate regression models, HAND status (b = -0.79, P < .001) and GDS impairment status (b = -0.83, P < .001) significantly predicted DETECT performance. Areas under the curve for DETECT were 0.78 for differentiating participants by HAND status (HAND vs no HAND) and 0.85 for detecting GDS impairment.ConclusionsThe DETECT cognition module provides a novel means to identify cognitive impairment in older PWH. As DETECT is fully immersive and self-administered, this virtual reality tool holds promise as a scalable cognitive screening battery.

Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aβ) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs. Current methods for detecting AD pathology, however, are often expensive and invasive, limiting wide and easy access to a clinical setting. A non-invasive, cost-efficient platform, such as computerized cognitive tests, could be potentially useful to identify at-risk individuals as early as possible. In this study, we examined the diagnostic value of an episodic memory task, the mnemonic discrimination task (MDT), for predicting risk of cognitive impairment or Aβ burden. We constructed a random forest classification algorithm, utilizing MDT performance metrics and various neuropsychological test scores as input features, and assessed model performance using area under the curve (AUC). Models based on MDT performance metrics achieved classification results with an AUC of 0.83 for cognitive status and an AUC of 0.64 for Aβ status. Our findings suggest that mnemonic discrimination function may be a useful predictor of progression to prodromal AD or increased risk of Aβ load, which could be a cost-efficient, noninvasive cognitive testing solution for potentially wide-scale assessment of AD pathological and cognitive risk.

Learning and memory mainly rely on correct synaptic function in the hippocampus and other brain regions. In Parkinsons disease, subtle cognitive deficits may even precede motor signs early in the disease. Hence, we set out to unravel the earliest hippocampal synaptic alterations associated with human α-synuclein overexpression prior to and soon after the appearance of cognitive deficits in a parkinsonism model. We bilaterally injected adeno-associated viral vectors encoding A53T-mutated human α-synuclein into the substantia nigra of rats, and evaluated them 1, 2, 4 and 16 weeks post-inoculation by immunohistochemistry and immunofluorescence to study degeneration and distribution of α-synuclein in the midbrain and hippocampus. The object location test was used to evaluate hippocampal-dependent memory. Sequential window acquisition of all theoretical mass spectrometry-based proteomics and fluorescence analysis of single-synapse long-term potentiation were used to study alterations to protein composition and plasticity in isolated hippocampal synapses. The effect of L-DOPA and pramipexole on long-term potentiation was also tested. Human α-synuclein was found within dopaminergic and glutamatergic neurons of the ventral tegmental area, and in dopaminergic, glutamatergic and GABAergic axon terminals in the hippocampus from 1 week post-inoculation, concomitant with mild dopaminergic degeneration in the ventral tegmental area. In the hippocampus, differential expression of proteins involved in synaptic vesicle cycling, neurotransmitter release and receptor trafficking, together with impaired long-term potentiation were the first events observed (1 week post-inoculation), preceding cognitive deficits (4 weeks post-inoculation). Later on, at 16 weeks post-inoculation, there was a deregulation of proteins involved in synaptic function, particularly those involved in the regulation of membrane potential, ion balance and receptor signalling. Hippocampal long-term potentiation was impaired before and soon after the onset of cognitive deficits, at 1 and 4 weeks post-inoculation, respectively. L-DOPA recovered hippocampal long-term potentiation more efficiently at 4 weeks post-inoculation than pramipexole, which partially rescued it at both time points. Overall, we found impaired synaptic plasticity and proteome dysregulation at hippocampal terminals to be the first events that contribute to the development of cognitive deficits in experimental parkinsonism. Our results not only point to dopaminergic but also to glutamatergic and GABAergic dysfunction, highlighting the relevance of the three neurotransmitter systems in the ventral tegmental area-hippocampus interaction from the earliest stages of parkinsonism. The proteins identified in the current work may constitute potential biomarkers of early synaptic damage in the hippocampus and hence, therapies targeting these could potentially restore early synaptic malfunction and consequently, cognitive deficits in Parkinsons disease.

OBJECTIVES: Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, that is, a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory, are a core feature of the disease. The present study sought to replicate this in a large cohort of well-characterized first-episode psychosis patients. We expected that patients in the highest anticholinergic burden group would exhibit the poorest verbal memory compared to those with low anticholinergic burden and healthy controls at baseline (3 months following admission). We further hypothesized that over time, at month 12, patients verbal memory performance would improve but would remain inferior to controls. METHODS: Patients (n  =  311; low anticholinergic burden [n  =  241] and high anticholinergic burden [n  =  70], defined by a Drug Burden Index cut-off of 1) and healthy controls (n  =  128) completed a clinical and neurocognitive battery including parts of the Wechsler Memory Scale at months 3 and 12. RESULTS: Cross-sectionally, using an analysis of variance, patients in the highest anticholinergic burden group had the poorest performance in verbal memory when compared to the other groups at month 3, F(2,430)  =  52.33, P

We examined the role of menopausal status in daily mood and cognitive performance among women with bipolar disorder (BD) compared to healthy comparison women. We analyzed the association of menopausal status, bipolar diagnosis, and their interaction on daily mood assessed by mobile surveys and attentional performance measured multiple times over 2 weeks. Menopausal status was associated with more daily negative affect in women with BD, but not related to attentional performance.

Context: This study investigated individual sociocognitive factors from the theory of planned behavior and their relationship to exercise for postconcussion recovery. Design and Methods: Four hundred and fifty-nine Australian adults, two-thirds of whom had no concussion history (66%), completed an online survey of their beliefs and attitudes toward exercise for postconcussion recovery. Secondary questions evaluated program design features that could affect engagement (eg, session frequency). Results: Structured equation modeling found that subjective norms were the strongest significant predictor of intention to participate in exercise for postconcussion recovery. Perceived behavioral control was also a significant predictor of intention to participate but to a lesser extent. Attitude did not predict participation intention. The design features identified as key were personalization and being supervised during the program. Conclusions: This study found that people's intention to participate in a program of exercise postconcussion recovery is shaped by individual psychological factors and identified program design features that could be adjusted for increased engagement. Program success could be maximized through strategies such as supporting individuals to have a stronger sense of control over their participation through the choice of session timing or frequency and harnessing the influence of significant others via supportive messaging from key professionals. [ABSTRACT FROM AUTHOR]

This study explored the acute effects of different running intensities on cognitive and motor performances in individuals with intellectual disability (ID). An ID group (age, M = 15.25 years, SD = 2.76) and a control group without ID (age, M = 15.11 years, SD = 1.54) performed visual simple and choice reaction times, auditory simple reaction time, and finger tapping tests before and after running at low or moderate intensity (30% and 60% of heart rate reserve [HRR], respectively). Visual simple reaction time values decreased (p <.001) after both intensities at all time points with higher (p =.007) extend after the 60% HRR intensity for both groups. After both intensities, the VCRT decreased (p <.001) in the ID group at all time points compared with preexercise (Pre-EX) while, in the control group, these values decreased (p <.001) only immediately (IM-EX) and after 10 min (Post-10) of exercise cessation. Compared withs Pre-EX, in the ID group, the auditory simple reaction time values decreased (p <.001) at all time points after the 30% HHR intensity whereas, after the 60% HRR, these values decreased only at IM-EX (p <.001), Post-10 (p =.001) and Post-20 (p <.001). In the control group, auditory simple reaction time values decreased (p =.002) only after the 30% HRR intensity at IM-EX. The finger tapping test increased at IM-EX (p <.001) and at Post-20 (p =.001) compared to Pre-EX in both groups only after the 30% HHR intensity and for the dominant hand. The effect of physical exercise on cognitive performances in individuals with ID seems to depend on the cognitive test type as well as the exercise intensity. [ABSTRACT FROM AUTHOR]