Poor Cognitive Outcomes Research Articles

Microglial TLR4 is Critical for Neuronal Injury and Cognitive Dysfunction in Subarachnoid Hemorrhage

BackgroundToll-like receptor 4 (TLR4) activation causes excessive production of proinflammatory mediators and an increased expression of costimulatory molecules that leads to neuroinflammation after subarachnoid hemorrhage (SAH). Although TLR4-mediated inflammatory pathways have long been studied in neuroinflammation, the specific glia implicated in initiation and propagation of neuroinflammation in SAH have not been well elucidated. In this study, we investigated the involvement of glial TLR4 including microglia and astrocytes in brain damage and poor neurological outcome.MethodsIn this study, global TLR4 knockout, cell-specific TLR4 knockout, and floxxed control male and female mice were used. The mice were injected with 60 μl autologous blood near the mesencephalon to induce SAH; animals were euthanized on postoperative day 7 for immunohistochemistry of glia and apoptotic cells. Microglial morphology was evaluated by using immunofluorescence density quantification to determine correlations between morphology and neuroinflammation. Microglial depletion was accomplished with the intracerebroventricular administration of clodronate liposomes. Cognitive function was assessed with Barnes maze.ResultsOn postoperative day 7 after SAH induction, neuronal apoptosis was markedly reduced in the clodronate liposome group compared with phosphate-buffered saline control liposomes, and cognitive performance in the clodronate group was improved, as well. Differences in microglial activation, assessed by morphometric analysis, and neuronal apoptosis were significantly greater in wildtype knockouts compared with cell-specific and global TLR4 knockouts. The mice lacking TLR4 on astrocytes and neurons showed no differences compared with wildtype mice on any end points.ConclusionsOur data suggest that microglial depletion with the intracerebroventricular administration of clodronate can improve the cognitive function in an SAH mouse model, and TLR4 is critical for microglial activation and neuronal injury. Only microglial TLR4 is necessary for brain damage and poor cognitive outcome rather than astrocyte or neuronal TLR4. Thus, microglial TLR4 could be a potent therapeutic target to treat SAH-associated neuronal injury and protect against cognitive dysfunction.

Mediation Analyses of the Role of Apathy on Motoric Cognitive Outcomes.

Recent literature indicates that apathy is associated with poor cognitive and functional outcomes in older adults, including motoric cognitive risk syndrome (MCR), a predementia syndrome. However, the underlying biological pathway is unknown. The objectives of this study were to (1) examine the cross-sectional associations between inflammatory cytokines (Interleukin 6 (IL-6) and C-Reactive Protein (CRP)) and apathy and (2) explore the direct and indirect relationships of apathy and motoric cognitive outcomes as it relates to important cognitive risk factors. N = 347 older adults (≥65 years old) enrolled in the Central Control of Mobility in Aging Study (CCMA). Linear and logic regression models showed that IL-6, but not CRP was significantly associated with apathy adjusted for age, gender, and years of education (β = 0.037, 95% CI: 0.002–0.072, p = 0.04). Apathy was associated with a slower gait velocity (β = −14.45, 95% CI: −24.89–4.01, p = 0.01). Mediation analyses demonstrated that IL-6 modestly mediates the relationship between apathy and gait velocity, while apathy mediated the relationships between dysphoria and multimorbidity and gait velocity. Overall, our findings indicate that apathy may be an early predictor of motoric cognitive decline. Inflammation plays a modest role, but the underlying biology of apathy warrants further investigation.

Associations among maternal lifetime trauma, psychological symptoms in pregnancy, and infant stress reactivity and regulation.

Maternal trauma has intergenerational implications, including worse birth outcomes, altered brain morphology, and poorer mental health. Research investigating intergenerational effects of maternal trauma on infant stress reactivity and regulation is limited. Maternal mental health during pregnancy may be a contributor: psychopathology is a sequela of trauma exposure and predictor of altered self-regulatory capacity in offspring of affected mothers. We assessed associations among maternal lifetime trauma and infant stress responsivity, mediated by psychological symptoms in pregnancy. Mothers reported lifetime trauma history and anxiety, depressive, and posttraumatic stress symptoms during pregnancy. At infant age 6 months, stress reactivity and regulation were assessed via maternal behavior ratings (Infant Behavior Questionnaire-Revised, IBQ-R) and behavioral (negative mood) and physiological (respiratory sinus arrhythmia, RSA) markers during a laboratory stressor (Still-Face Paradigm). Maternal trauma was directly associated with lower infant physiological regulation and indirectly associated with lower levels of both infant behavioral and physiological regulation via higher maternal anxiety during pregnancy. Maternal trauma was also indirectly associated with higher infant reactivity via higher maternal anxiety during pregnancy. Post hoc analyses indicated differential contributions of maternal prenatal versus postnatal anxiety to infant outcomes. Findings highlight potential contributory mechanisms toward maladaptive child stress response, which has been associated with poor behavioral, cognitive, and academic outcomes.

0437 Psychometric Evaluation of the Insomnia Severity Index in Nurses

Abstract Introduction This secondary analysis was conducted to examine the psychometric properties of the Insomnia Severity Index (ISI) in a sample of non-shift working nurses. Insomnia is a common sleep disorder and has been linked to poor physical, psychological, and cognitive outcomes and increased accidents. Unique features of this sample (e.g., long shifts, patient care, quick emergency response) create a need for population-specific validation of the commonly used ISI. Study I assessed convergent and discriminant validity between the ISI, sleep diary, and other sleep and psychosocial measures. Study II assessed the test-retest validity of the ISI. Methods Participants (N = 289) were nurses from two regional hospitals in north Texas recruited for a parent study (268 females, M age = 40.67 years; SD = 11.03; 79.9% White) who completed daily sleep diaries and sleep and mental health screeners at four timepoints. Shift workers and participants who did not complete the ISI at baseline were excluded from the analysis. Results The ISI had medium to large correlations with measures intended to establish convergent validity including sleep onset latency (r = .41), wake time after sleep onset (r = .40), sleep efficiency (r = -.45), sleep quality (r = .66), and sleep related impairment (r = .67). Examination of ISI items and analogous sleep diary parameters showed small to large correlations (rs = .13-.53). The ISI had small to large correlations with measures intended to establish discriminant validity including nightmares (r = .25), circadian preference (r = -.26), shiftwork-related disorders (r = .09) and PTSD (r = .36), depression (r = .69), anxiety (r = .51), and perceived stress (r = .43). The ISI demonstrated good test-retest reliability from baseline to 1-month (ICC = .88), 6-month (ICC = .77), and 11-month follow up (ICC = .74). Conclusion The ISI demonstrated good psychometric properties and is a psychometrically strong measure for the assessment of insomnia severity in nurses. Overlap with psychological symptoms suggests caution while interpreting these constructs. Support (If Any) This study was supported by a grant from the National Institute of Allergy and Infectious Diseases, Grant/Award Number: R01AI128359-01.

Maternal Social Risk, Gestational Age at Delivery, and Cognitive Outcomes among Adolescents Born Extremely Preterm.

Children born extremely preterm (EP) are at increased risk of cognitive deficits that persist into adulthood. Few large cohort studies have examined differential impairment of cognitive function in EP-born adolescents in relation to early life risk factors, including maternal social disadvantage, gestational age at delivery, and neonatal morbidities prevalent among EP neonates. To assess cognitive abilities in relation to early life risk factors in an EP-born cohort at 15 years of age. 681 of 1198 surviving participants (57%) enrolled from 2002 to 2004 in the Extremely Low Gestational Age Newborn Study returned at age 15 years for an assessment of cognitive abilities with the Wechsler Abbreviated Scale of Intelligence-II and the NIH Toolbox Cognition Battery (NTCB) verbal cognition and fluid processing composites, the latter of which measured executive functions and processing speed. Three cognitive outcomes, WASI-II IQ, NTCB verbal cognition, and NTCB fluid processing, were analyzed for associations with maternal social disadvantage and gestational age. Mediation of maternal social disadvantage by gestational age and mediation of gestational age by neonatal morbidities were also examined. Test scores were lower for NTCB fluid processing relative to IQ and NTCB verbal abilities. Social disadvantage and gestational age were associated with all three cognitive outcomes. Mediation analyses indicated partial mediation of gestational age associations with all three outcomes by neonatal morbidities but did not support mediation by gestational age of social risk associations with cognitive outcomes. Greater maternal social disadvantage and lower gestational age are associated with less favorable cognitive outcomes among EP-born adolescents at 15 years of age. Neonatal morbidities partially mediate associations between lower gestational age and cognitive outcomes. These findings highlight the need for improved medical and remedial interventions to mitigate risk of poor cognitive outcomes among EP-born adolescents.

Multimodal magnetic resonance neuroimaging measures characteristic of early cART-treated pediatric HIV: A feature selection approach.

Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV‐related brain alterations can be investigated separately using proton magnetic resonance spectroscopy (1H‐MRS), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI), a set of multimodal MRI measures characteristic of children on cART has not been previously identified. We used the embedded feature selection of a logistic elastic‐net (EN) regularization to select neuroimaging measures that distinguish CPHIV from controls and measured their classification performance via the area under the receiver operating characteristic curve (AUC) using repeated cross validation. We also wished to establish whether combining MRI modalities improved the models. In single modality analysis, sMRI volumes performed best followed by DTI, whereas individual EN models on spectroscopic, gyrification, and cortical thickness measures showed no class discrimination capability. Adding DTI and 1H‐MRS in basal measures to sMRI volumes produced the highest classification performance validation accuracy=85%AUC=0.80. The best multimodal MRI set consisted of 22 DTI and sMRI volume features, which included reduced volumes of the bilateral globus pallidus and amygdala, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the right corticospinal tract in cART‐treated CPHIV. Consistent with previous studies of CPHIV, select subcortical volumes obtained from sMRI provide reasonable discrimination between CPHIV and controls. This may give insight into neuroimaging measures that are relevant in understanding the effects of HIV on the brain, thereby providing a starting point for evaluating their link with cognitive performance in CPHIV.

Predictors of cognitive gains during inpatient rehabilitation for older adults with traumatic brain injury.

Traumatic brain injury (TBI) among older adults is increasing and can affect cognition. To effectively meet the rehabilitation needs of older adults, a clearer picture is needed of patient-, clinical-, and facility-level characteristics that affect cognitive recovery during inpatient rehabilitation facility (IRF) stays. To identify patient, clinical, and facility factors associated with cognitive recovery among older adults with TBI who received IRF care. Secondary data analysis. Uniform Data System for Medical Rehabilitation-participating IRFs in the United States. Patients were 65 to 99 years of age at IRF admission for TBI. Participants received IRF care between 2002 and 2018 (N=137,583); 56.3% were male; 84.2% were white; mean age was 78.7 years. Change in Functional Independence Measure Cognitive Score (FIM-Cognitive) from IRF admission to discharge, categorized as favorable (FIM-cognitive score gains ≥3 points) or poor (FIM-cognitive score gains <3 points) cognitive outcomes. Not applicable. Patients had greater odds of favorable cognitive recovery if they were female (adjusted odds ratio [aOR] 1.05, 95% confidence interval [CI] 1.05-1.08), had higher motor functioning at IRF admission (aOR 1.03, 95% CI 1.03-1.04), longer length of stay (aOR 1.07, 95% CI 1.06-1.07), or received care at a freestanding IRF (vs. hospital rehab unit) (aOR 1.57, 95% CI 1.52-1.61). Patients who were older (aOR 0.99, 95% CI 0.98-0.99), Black (aOR 0.79, 95% CI 0.75-0.83), Hispanic or Latino (aOR 0.97, 95% CI 0.91-1.02), or were part of another racial or ethnic group (aOR 0.85, 95% CI 0.81-0.90) (vs. White), had high-cost comorbid conditions (aOR 0.71, 95% CI 0.65-0.76), or who had higher cognitive functioning at IRF admission (aOR 0.90, 95% CI 0.90-0.91) had lower odds of favorable cognitive recovery. Patient (age, sex, race, ethnicity), clinical (level of functioning at IRF admission, length of stay) and facility (e.g., freestanding IRF) factors contributed to the cognitive recoveries of older adults during IRF stays.

Post Stroke Delirium Does Not Predict Poor Cognitive Outcome at Discharge in Patients with Acute Ischemic Stroke (P8-10.004)

Post Stroke Delirium Does Not Predict Poor Cognitive Outcome at Discharge in Patients with Acute Ischemic Stroke (P8-10.004)

Are subtypes of affective symptoms differentially associated with change in cognition over time: A latent class analysis

BackgroundIn the absence of disease-modifying treatments, identifying potential psychosocial risk factors for dementia is paramount. Depression and anxiety have been identified as potential risk factors. Studies however have yielded mixed findings, lending possibility to the fact that potential constellations of co-occurring depression and anxiety symptoms may better explain the link between affective symptoms and cognitive decline. MethodsData from participants (aged 50 and above) of the PROTECT study was used. Latent Class Analysis (LCA) was conducted on 21,684 participants with baseline anxiety and depression measures. Multiple linear regressions models, using a subset of these participants (N = 6136) who had complete cognition data at baseline and at 2-year follow-up, were conducted to assess for associations between class membership and longitudinal changes in cognition. ResultsThe LCA identified a 5-class solution: “No Symptoms”, “Sleep”, “Sleep and Worry”, “Sleep and Anhedonia”, and “Co-morbid Depression and Anxiety”. Class membership was significantly associated with longitudinal change in cognition. Furthermore, this association differed across different cognitive measures. LimitationsLimitations included significant attrition and a generally healthy sample which may impact generalisability. ConclusionsSubstantial heterogeneity in affective symptoms could explain previous inconsistent findings concerning the association between affective symptoms and cognition. Clinicians should not focus solely on total symptom scores on a single affective domain, but instead on the presence and patterns of symptoms (even if sub-clinical) on measures across multiple affective domains. Identifying particular subgroups that are at greater risk of poor cognitive outcomes may support targeted prevention work.

Relationships between maternal body mass index and child cognitive outcomes at 3 years of age are buffered by specific early environments in a prospective Canadian birth cohort.

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler's Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother-child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; -2.01 [-3.43, -0.59], p = 0.006), verbal composite (-1.93 [-3.33, -0.53], p = 0.007), and information scale (-0.41 [-0.70, -0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%-41% and 7%-22%, respectively, and accounted for approximately 5%-10% greater variation in male children's cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.

Gestational and Lactational Iron Deficiency Anemia Impairs Myelination and the Neurovascular Unit in Infant Rats.

Iron deficiency anemia is a prevalent health problem among pregnant women and infants, particularly in the developing countries that causes brain development deficits and poor cognitive outcomes. Since tissue iron depletion may impair myelination and trigger cellular hypoxic signaling affecting blood vessels, we studied myelination and the neurovascular unit (NVU) in infant rats born to mothers fed with an iron deficient (ID) or control diet from embryonic day 5 till weaning. Blood samples and brains of rat pups at postnatal day (PND) 14 and 30 were analyzed. PND 14 ID rats had severe microcytic hypochromic anemia that was almost reversed at PND 30 although hypomyelination and astrocyte immature phenotype in the corpus callosum were significant at that age. In CA1 hippocampal region, PND 14 and PND 30 ID rats showed significant reduced expression of the receptor β of the platelet-derived growth factor localized in pericytes and associated to aquaporin 4 (AQP4) immunopositive capillaries. Shorter AQP4 + capillaries and reduced AQP4 expression were also evidenced in PND 14 and PND 30 ID rats. In addition, pericyte membrane permeability through large-pore channels was transiently increased in ID rats at PND 14 but not at PND 30, while the blood-brain barrier permeability was not affected. Remarkably, transient increased pericyte permeability found in PND 14 ID rats was not directlyrelated to iron depletion, suggesting the involvement of other iron deficiency anemia-induced mechanisms. In summary, severe ID during gestation and lactation produces persistent hypomyelination and significantly affects hippocampal pericytes and astrocytes in the NVU which may trigger impaired neurovascular function.

Identifying Racial and Rural Disparities of Cognitive Functioning Among Older Adults: The Role of Social Isolation and Social Technology Use.

Social isolation is associated with poorer cognitive outcomes among older adults. The use of online social technology platforms may provide a means to reduce social isolation. However, research examining whether social technology can mitigate the negative effects of social isolation on cognitive functioning is limited. This study investigates the interaction between social isolation and social technology use on cognitive functioning among older adults and seeks to identify racial and rural-urban differences in this relationship. Data were obtained from the Health and Retirement Study 2014-2018 waves (N = 5,358). Participants (aged 50-102) completed self-report measures of social isolation, loneliness, and frequency of online social communication and completed the modified Telephone Interview for Cognitive Status, which assesses cognitive functioning. Examinations of race focused on differences between Black/African American and White/Caucasian groups; rurality was operationalized using Beale Rural-Urban Continuum Codes. Data were analyzed using structural equation models. Social technology use moderated the negative relationship between social isolation and cognitive functioning, controlling for age, education, gender, wealth, and general computer usage. Greater social technology use was associated with better cognitive functioning among socially isolated older adults. Results showed evidence of racial, but not rural-urban, differences in the relationship between social technology use and cognitive functioning. Regardless of the degree of social isolation, frequent social technology use was associated with improved cognitive functioning in Black/African American older adults but not White/Caucasians older adults. Social technology may represent a way to mitigate cognitive decline, particularly among Black/African American older adults.

Spotlight on the March 22 Issue

#### Notable in Neurology This Week This issue features an article that evaluates long-term health care costs of surgery in children with drug-resistant epilepsy; another defines and determines predictability of poor cognitive outcome 1 year after mild traumatic brain injury. A featured Special Article provides a practice advisory update from the American Academy of Neurology for stroke prevention in patients with symptomatic intracranial atherosclerotic arterial stenosis. ### Magnetic Resonance Spectroscopy of Hypoxic-Ischemic Encephalopathy After Cardiac Arrest ![Graphic][1]</img> In this … [1]: /embed/inline-graphic-1.gif

Maternal depressive symptoms and children's cognitive school readiness: the role of gene-environment interplay.

Maternal depressive symptoms are a robust risk factor for poor cognitive outcomes in children, yet the role of gene-environment interplay in this association is not well understood. The objective of this study was to evaluate gene-environment interaction in the association between maternal depressive symptoms and children's cognitive school readiness. Data come from a population-based birth cohort of 538 twin pairs. Maternal depressive symptoms were self-reported (Centre for Epidemiologic Studies Depression Scale) when children were aged 6 and 18 months (a mean score was used). Children's cognitive school readiness was assessed using the Lollipop Test when children were aged 5 years. Analyses were conducted with structural equation modeling. Maternal depressive symptoms were correlated with children's cognitive school readiness (r = -0.10). Shared environmental factors explained most of the variance in children's cognitive school readiness (52%). The remaining variance was accounted for by genetic (30%) and nonshared environmental factors (18%). As the level of maternal depressive symptoms increased, the relative contribution of nonshared environmental factors to the variance in children's cognitive school readiness increased (0.14 [95% CI: 0.04 to 0.24]), whereas the relative contribution of genetic factors decreased (-0.28 [-0.64 to 0.08]). In contexts of elevated maternal depressive symptoms, environmental - and potentially modifiable - factors may be especially important for shaping children's cognitive outcomes. This suggests that interventions to improve the early childhood environment of children exposed to maternal depressive symptoms may improve their cognitive outcomes.

Diagnosis and Management of Opsoclonus-Myoclonus-Ataxia Syndrome in Children: An International Perspective.

Background and ObjectivesOpsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder of the nervous system that classically presents with a combination of characteristic eye movement disorder and myoclonus, in addition to ataxia, irritability, and sleep disturbance. There is good evidence that OMAS is an immune-mediated condition that may be paraneoplastic in the context of neuroblastoma. This syndrome may be associated with long-term cognitive impairment, yet it remains unclear how this is influenced by disease course and treatment. Treatment is largely predicated on immune suppression, but there is limited evidence to indicate an optimal regimen.MethodsFollowing an international multiprofessional workshop in 2004, a body of clinicians and scientists comprising the International OMS Study group continued to meet biennially in a joint professionals and family workshop focusing on pediatric OMAS. Seventeen years after publication of the first report, a writing group was convened to provide a clinical update on the definitions and clinical presentation of OMAS, biomarkers and the role of investigations in a child presenting with OMAS, treatment and management strategies including identification and support of long-term sequelae.ResultsThe clinical criteria for diagnosis were reviewed, with a proposed approach to laboratory and radiologic investigation of a child presenting with possible OMAS. The evidence for an upfront vs escalating treatment regimen was reviewed, and a treatment algorithm proposed to recognize both these approaches. Importantly, recommendations on monitoring of immunotherapy response and longer-term follow-up based on an expert consensus are provided.DiscussionOMAS is a rare neurologic condition that can be associated with poor cognitive outcomes. This report proposes an approach to investigation and treatment of children presenting with OMAS, based on expert international opinion recognizing the limited data available.

Neurodevelopmental Outcomes following Preterm Birth and the Association with Postmenstrual Age at Discharge.

This study aimed to (1) define the prevalence of motor, cognitive, and language delays in preterm infants born <32 weeks estimated gestational age (EGA); and (2) identify the relationship between the timing of discharge from the neonatal intensive care unit (NICU) and neurodevelopmental outcome in early childhood. This retrospective study of 172 preterm infants born <32 weeks EGA and hospitalized in a level-IV NICU captured medical factors, including timing of discharge, from the NICU stay. Standardized developmental testing at 1 to 2 years corrected age was conducted in the newborn follow-up clinic. At 1 to 2 years corrected age, the sample had an average Bayley Scales of Infant and Toddler Development (Bayley-III) cognitive composite score of 91.5 ± 17.4, language composite score of 84.5 ± 17.3, and motor composite score of 88.9 ± 18.4. Lower EGA at birth, necrotizing enterocolitis, patent ductus arteriosus, and oxygen requirement for >28 days were independently associated with higher postmenstrual age (PMA) at NICU discharge. Higher PMA at discharge was associated with poorer cognitive outcome [p < 0.001, β = -1.1 (-1.6, -0.7)], poorer language outcome [p = 0.049, β = -0.5 (-0.9, -0.003)], and poorer motor outcome [p <0.001, β = -1.0 (-1.5, -0.5)]. For every additional week of hospitalization, scores were an average of 1.1 points lower in cognitive, 1.0 point lower in motor, and 0.5 points lower in language domains of the Bayley-III assessment. Poorer cognitive, language, and motor outcomes were associated with longer hospitalization, even after controlling for medical risk factors known to be associated with poorer outcome. This provides further evidence for the potential role of the environment in impacting developmental outcomes of infants hospitalized in the NICU. · There are high rates of developmental impairment among preterm infants born <32 weeks at 1 year to 2 years.. · The longer the infant is exposed to the NICU environment, the higher the risk of neurodevelopmental challenges.. · These findings provide increased motivation for optimizing the early NICU environment..

Cognitive Outcome 1 Year After Mild Traumatic Brain Injury: Results From the TRACK-TBI Study.

The objectives of this study were to develop and establish concurrent validity of a clinically relevant definition of poor cognitive outcome 1 year after mild traumatic brain injury (mTBI), to compare baseline characteristics across cognitive outcome groups, and to determine whether poor 1-year cognitive outcome can be predicted by routinely available baseline clinical variables. Prospective cohort study included 656 participants ≥17 years of age presenting to level 1 trauma centers within 24 hours of mTBI (Glasgow Coma Scale score 13-15) and 156 demographically similar healthy controls enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Poor 1-year cognitive outcome was defined as cognitive impairment (below the ninth percentile of normative data on ≥2 cognitive tests), cognitive decline (change score [1-year score minus best 2-week or 6-month score] exceeding the 90% reliable change index on ≥2 cognitive tests), or both. Associations of poor 1-year cognitive outcome with 1-year neurobehavioral outcomes were performed to establish concurrent validity. Baseline characteristics were compared across cognitive outcome groups, and backward elimination logistic regression was used to build a prediction model. Mean age of participants with mTBI was 40.2 years; 36.6% were female; 76.6% were White. Poor 1-year cognitive outcome was associated with worse 1-year functional outcome, more neurobehavioral symptoms, greater psychological distress, and lower satisfaction with life (all p < 0.05), establishing concurrent validity. At 1 year, 13.5% of participants with mTBI had a poor cognitive outcome vs 4.5% of controls (p = 0.003). In univariable analyses, poor 1-year cognitive outcome was associated with non-White race, lower education, lower income, lack of health insurance, hyperglycemia, preinjury depression, and greater injury severity (all p < 0.05). The final multivariable prediction model included education, health insurance, preinjury depression, hyperglycemia, and Rotterdam CT score ≥3 and achieved an area under the curve of 0.69 (95% CI 0.62-0.75) for the prediction of a poor 1-year cognitive outcome, with each variable associated with >2-fold increased odds of poor 1-year cognitive outcome. Poor 1-year cognitive outcome is common, affecting 13.5% of patients with mTBI vs 4.5% of controls. These results highlight the need for better understanding of mechanisms underlying poor cognitive outcome after mTBI to inform interventions to optimize cognitive recovery.

Personalized Prediction of Postconcussive Working Memory Decline: A Feasibility Study

Concussion, also known as mild traumatic brain injury (mTBI), commonly causes transient neurocognitive symptoms, but in some cases, it causes cognitive impairment, including working memory (WM) deficit, which can be long-lasting and impede a patient’s return to work. The predictors of long-term cognitive outcomes following mTBI remain unclear, because abnormality is often absent in structural imaging findings. Previous studies have demonstrated that WM functional activity estimated from functional magnetic resonance imaging (fMRI) has a high sensitivity to postconcussion WM deficits and may be used to not only evaluate but guide treatment strategies, especially targeting brain areas involved in postconcussion cognitive decline. The purpose of the study was to determine whether machine learning-based models using fMRI biomarkers and demographic or neuropsychological measures at the baseline could effectively predict the 1-year cognitive outcomes of concussion. We conducted a prospective, observational study of patients with mTBI who were compared with demographically matched healthy controls enrolled between September 2015 and August 2020. Baseline assessments were collected within the first week of injury, and follow-ups were conducted at 6 weeks, 3 months, 6 months, and 1 year. Potential demographic, neuropsychological, and fMRI features were selected according to their significance of correlation with the estimated changes in WM ability. The support vector machine classifier was trained using these potential features and estimated changes in WM between the predefined time periods. Patients demonstrated significant cognitive recovery at the third month, followed by worsened performance after 6 months, which persisted until 1 year after a concussion. Approximately half of the patients experienced prolonged cognitive impairment at the 1-year follow up. Satisfactory predictions were achieved for patients whose WM function did not recover at 3 months (accuracy = 87.5%), 6 months (accuracy = 83.3%), and 1 year (accuracy = 83.3%) and performed worse at the 1-year follow-up compared to the baseline assessment (accuracy = 83.3%). This study demonstrated the feasibility of personalized prediction for long-term postconcussive WM outcomes based on baseline fMRI and demographic features, opening a new avenue for early rehabilitation intervention in selected individuals with possible poor long-term cognitive outcomes.

Rural/urban dwelling across the life-course and late-life cognitive ability in Mexico

BackgroundUrban advantages in older adults’ cognitive function have been observed. Less is known about early-life urban dwelling and late-life cognition. We evaluate how rural/urban dwelling throughout life and rural to urban shifts in life relate with cognition in Mexico, a country experiencing aging and urbanization. MethodsData came from the 2003 and 2012 Mexican Health and Aging Study (n = 12,238 adults age 50+). Early-life urban dwelling was self-reported. Late-life urban dwelling was based on population size of respondents’ community of residence (community 2500+ people) at the time of survey. Cognitive function was measured across several cognitive tasks. We assess differences in baseline cognitive function and nine-year decline across groups using a latent change score model. ResultsCross-sectionally, compared to always rural dwellers, rural-urban transitions were associated with cognitive benefits, though individuals residing in urban areas continuously through life exhibited the highest levels of cognitive function (β = 0.89, 95% CI: 0.83, 0.96) even after adjusting for SES, health, and health behaviors (β = 0.28, 95% CI: 0.22, 0.35). Longitudinally, always urban dwellers exhibited slower decline than always rural dwellers when adjusting for baseline cognition (β = 0.11, 95% CI: 0.03, 0.18), though faster decline when baseline cognition was not adjusted (β = −0.11, 95% CI: -0.18, −0.04). No differences were observed for cognitive change across comparison groups after adjusting for potential mechanisms. ConclusionsEarly- and late-life urban dwelling may result in cognitive advantages for older Mexican adults. Clinicians should consider where individuals resided throughout life to better understand a patient's likelihood of experiencing poor cognitive outcomes.

Handgrip strength and risk of cognitive outcomes: new prospective study and meta-analysis of 16 observational cohort studies

Handgrip strength (HGS), a measure of muscular strength, might be a risk indicator for cognitive functioning, but the evidence is not consistent. Using a new prospective study and meta-analysis of published observational cohort studies, we aimed to evaluate the prospective associations of HGS with poor cognitive outcomes including cognitive impairment, dementia and Alzheimer’s disease (AD). Handgrip strength, measured using a Martin-Balloon-Vigorimeter, was assessed at baseline in a population-based sample of 852 men and women with good cognitive function in the Kuopio Ischemic Heart Disease cohort. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for cognitive outcomes. Relevant published studies were sought in MEDLINE, Embase and Web of Science from inception until October 2021 and pooled using random effects meta-analysis. During a median follow-up of 16.6 years, 229 dementia cases were recorded. Comparing extreme tertiles of HGS, the multivariable adjusted HR (95% CI) for dementia, AD and vascular dementia was 0.77 (0.55–1.07), 0.75 (0.52–1.10) and 0.49 (0.16–1.48), respectively. In a meta-analysis of 16 population-based prospective cohort studies (including the current study) comprising 180,920 participants, the pooled multivariable adjusted relative risks (95% CIs) comparing the top vs bottom thirds of HGS levels were as follows: 0.58 (0.52–0.65) for cognitive impairment; 0.37 (0.07–1.85) for cognitive decline; 0.73 (0.62–0.86) for dementia; 0.68 (0.53–0.87) for AD; and 0.48 (0.32–0.73) for vascular dementia. GRADE quality of evidence ranged from low to very low. Meta-analysis of aggregate prospective data suggests that HGS may be a risk indicator for poor cognitive outcomes such as cognitive impairment, dementia and AD. Systematic review registration: PROSPERO 2021: CRD42021237750.