Risk Factors For Cognitive Deficits Research Articles

Age-Related Changes in Sleep and Its Implications for Cognitive Decline in Aging Persons With Schizophrenia: A Critical Review.

Cognitive impairment is a core feature of schizophrenia that worsens with aging and interferes with quality of life. Recent work identifies sleep as an actionable target to alleviate cognitive deficits. Cardinal non-rapid eye movement (NREM) sleep oscillations such as sleep spindles and slow oscillations are critical for cognition. People living with schizophrenia (PLWS) and their first-degree relatives have a specific reduction in sleep spindles and an abnormality in their temporal coordination with slow oscillations that predict impaired memory consolidation. While NREM oscillatory activity is reduced in typical aging, it is not known how further disruption in these oscillations contributes to cognitive decline in older PLWS. Another understudied risk factor for cognitive deficits among older PLWS is obstructive sleep apnea (OSA) which may contribute to cognitive decline. We conducted a narrative review to examine the published literature on aging, OSA, and NREM sleep oscillations in PLWS. Spindles are propagated via thalamocortical feedback loops, and this circuitry shows abnormal hyperconnectivity in schizophrenia as revealed by structural and functional MRI studies. While the risk and severity of OSA increase with age, older PLWS are particularly vulnerable to OSA-related cognitive deficits because OSA is often underdiagnosed and undertreated, and OSA adds further damage to the circuitry that generates NREM sleep oscillations. We highlight the critical need to study NREM sleep in older PWLS and propose that identifying and treating OSA in older PLWS will provide an avenue to potentially mitigate and prevent cognitive decline.

Possible mechanisms involved in the neuroprotective effects of chrysin against mild traumatic brain injury-induced spatial cognitive decline: An in vivo study in a rat model

Traumatic brain injury (TBI) is recognized as an important risk factor for cognitive deficits. The present study was designed to determine the potential neuroprotective effects of chrysin, a natural flavonoid compound, against TBI-induced spatial cognitive decline and the possible mechanisms involved. Oral administration of chrysin (25, 50, or 100 mg/kg/day) was initiated in rats immediately following the induction of the diffuse TBI model using the weight-dropping Marmarou model. Spatial cognitive ability, hippocampal synaptic plasticity, blood-brain barrier (BBB) permeability, brain water content, and histological changes were assessed at scheduled time points. The animals subjected to TBI exhibited spatial cognitive decline in the Morris water maze (MWM) test, which was accompanied by inhibition of hippocampal long-term potentiation (LTP) induction at the perforant path-dentate gyrus (PP-DG) synapses. Additionally, TBI caused BBB disruption, brain edema, and neuronal loss. Interestingly, treatment with chrysin (especially in the dose of 100 mg/kg) alleviated all the above-mentioned neuropathological changes related to TBI. The results provide evidence that chrysin improves TBI-induced spatial cognitive decline, which may be partly related to the amelioration of hippocampal synaptic dysfunction, alleviation of BBB disruption, reduction of brain edema, and prevention of neuronal loss.

Use of modified Telephone Interview for Cognitive Status (TICS‐M) for cognitive impairment analysis one year after COVID‐19 hospitalization in Brazil

AbstractBackgroundCOVID‐19 infection primarily affects the respiratory system despite of short and medium‐term cognitive impairment has been increasingly reported. The Modified Telephone Interview for Cognitive Status (TICS‐M), validated for cognitive screening after stroke, assesses domains such as orientation, attention/calculation, language, and immediate and delayed episodic memory. Thus, the TICS‐M might be useful to remotely screen for cognitive impairment in individuals affected by COVID‐19.MethodCross‐sectional multicenter study in Belo Horizonte, Brazil, with participants hospitalized with COVID‐19 confirmed by RT‐PCR or serology. All patients were aged 18+ years. Clinical and sociodemographic data were obtained through electronic medical records and/or interviews. Cognitive impairment screening was performed one year after hospital admission using the TICS‐M, with a cutoff point of 14 out of 39.ResultNinety‐six patients were submitted to the test, of which 50 (52.1%) were women, 72 (75%) were self‐declared non‐white, 59 (64.15%) did not complete elementary school and the median age was 62 years (interquartile range 49‐69). There was no significant association between lower TICS‐M scores and sociodemographic data or previous medical history, except for higher educational level that appears to be a protective factor to lower scores on TICS‐M (OR 0.089, 95% CI:0,01‐0,7, p 0.008), which is demonstrated in Table 1. There was also no association between the scores and the clinical course during hospitalization as displayed in Table 2. Furthermore, length of hospital stay (p = 0.232) and length of stay in Intensive Care Unit (p = 0.565) did not impact the scores.ConclusionIn this study, 15% of the sample had cognitive impairment one year after hospitalization for COVID‐19 according to TICS‐M. The absence of an association between known risk factors for cognitive deficits and worse scores on the TICS‐M might have been influenced by the fact that only 13.5% of our sample did not have comorbidities. Lower education level was the only factor associated with worse scores, which indicates a possible need to adapt the test or the cutoff point for different educational levels.

Neurocognitive deficits may not resolve following pediatric kidney transplantation.

Pediatric chronic kidney disease (CKD) patients are at risk for cognitive deficits with worsening disease progression. Limited, existing cross-sectional studies suggest that cognitive deficits may improve following kidney transplantation. We sought to assess cognitive performance in relationship to kidney transplantation and kidney-specific medical variables in a sample of pediatric kidney transplant patients who provided cross-sectional and longitudinal observations. A retrospective chart review was conducted in patients who completed pre- and/or post-transplant neurocognitive testing at the University of Iowa from 2015-2021. Cognitive outcomes were investigated with developmentally appropriate, standardized measures. Mixed linear models estimated the impact of transplant status on cognitive function (z-scores). Subsequent post-hoc t-tests on change scores were limited to patients who had provided pre- and post-transplant assessments. Thirty eight patients underwent cognitive assessments: 10 had both pre- and post-transplant cognitive assessments, 11 had pre-transplant assessments only, and 17 had post-transplant data only. Post-transplant status was associated with significantly lower full-scale IQ and slower processing speed compared to pre-transplant status (estimate=-0.32, 95% confidence interval [CI]=-0.52: -0.12; estimate=-0.86, CI=-1.17: -0.55, respectively). Post-hoc analyses confirmed results from the mixed models (FSIQ change score=-0.34, 95% CI=-0.56: -0.12; processing speed change score=-0.98, CI=-1.28: -0.68). Finally, being ≥80months old at transplant was associated with substantially lower FSIQ compared to being <80 months (estimate=-1.25, 95% CI=-1.94: -0.56). Our results highlight the importance of monitoring cognitive function following pediatric kidney transplant and identify older transplant age as a risk factor for cognitive deficits.

Clinical features and cognitive sequelae in COVID-19: a retrospective study on N=152 patients

BackgroundThe novel human coronavirus (SARS-CoV-2) shows neurotropism and systemically affects the central nervous system (CNS). Cognitive deficits have been indeed reported as both short- and long-term sequelae of SARS-CoV-2 infection. However, the association between these disturbances and background/disease-related clinical features remains elusive. This work aimed at exploring how post-infective cognitive status relates to clinical/treatment outcomes by controlling for premorbid/current risk factors for cognitive deficits.MethodsCognitive measures (Mini-Mental State Examination, MMSE) of N=152 COVID-19 patient were retrospectively assessed in relation to disease severity, intensive care unit (ICU) admission, steroidal treatment, and occurrence of other viral/bacterial infections by controlling for remote/recent/COVID-19-related risk factors for cognitive deficits (at-risk vs. not-at-risk: Neuro+ vs. Neuro−).ResultsDescriptively, impaired MMSE performances were highly prevalent in mild-to-moderate patients (26.3%). ICU-admitted patients made less errors (p=.021) on the MMSE than those not admitted when partialling out risk factors and age—the latter negatively influencing performances. When addressing Neuro− patients only, steroidal treatment appears to improve MMSE scores among those suffering from other infections (p=.025).DiscussionCognitive sequelae of COVID-19 are likely to arise from a complex interplay between background/clinical premorbid features and disease-related/interventional procedures and outcomes. Mild-to-moderate patients requiring assistive ventilation who however are not admitted to an ICU are more likely to suffer from cognitive deficits—despite their etiology remaining elusive.

Alcohol, coffee and tea intake and the risk of cognitive deficits: a dose-response meta-analysis.

Lifestyle interventions are an important and viable approach for preventing cognitive deficits. However, the results of studies on alcohol, coffee and tea consumption in relation to cognitive decline have been divergent, likely due to confounds from dose-response effects. This meta-analysis aimed to find the dose-response relationship between alcohol, coffee or tea consumption and cognitive deficits. Prospective cohort studies or nested case-control studies in a cohort investigating the risk factors of cognitive deficits were searched in PubMed, Embase, the Cochrane and Web of Science up to 4th June 2020. Two authors searched the databases and extracted the data independently. We also assessed the quality of the studies with the Newcastle-Ottawa scale. Stata 15.0 software was used to perform model estimation and plot the linear or nonlinear dose-response relationship graphs. The search identified 29 prospective studies from America, Japan, China and some European countries. The dose-response relationships showed that compared to non-drinkers, low consumption (<11 g/day) of alcohol could reduce the risk of cognitive deficits or only dementias, but there was no significant effect of heavier drinking (>11 g/day). Low consumption of coffee reduced the risk of any cognitive deficit (<2.8 cups/day) or dementia (<2.3 cups/day). Green tea consumption was a significant protective factor for cognitive health (relative risk, 0.94; 95% confidence intervals, 0.92-0.97), with one cup of tea per day brings a 6% reduction in risk of cognitive deficits. Light consumption of alcohol (<11 g/day) and coffee (<2.8 cups/day) was associated with reduced risk of cognitive deficits. Cognitive benefits of green tea consumption increased with the daily consumption.

Neuropsychological correlates of obstructive sleep apnea severity in patients with epilepsy.

Obstructive sleep apnea affects up to 30% of patients with epilepsy. As obstructive sleep apnea represents a clinical risk factor for cognitive deficits, its occurrence in epilepsy patients may exacerbate cognitive deficits associated with this condition. However, the cognitive burden of obstructive sleep apnea in epilepsy remains poorly understood. We conducted a retrospective record review of adults with epilepsy who underwent a polysomnography and a neuropsychological assessment at Brigham and Women's Hospital. We examined the relationship between obstructive sleep apnea severity and cognitive functioning, particularly attention/executive functions, memory, and processing speed in untreated obstructive sleep apnea patients with epilepsy. Twenty patients with epilepsy and mild-to-severe obstructive sleep apnea were included in the analyses. We found significant positive correlations between the oxygen saturation levels during rapid-eye-movement sleep and attention/executive tests (p<0.05), as well as time spent with saturation levels ≤90% and executive functioning (p=0.008). Similarly, worse verbal memory performances were associated with lower oxygen levels (p=0.003). In addition, more severe respiratory events during rapid-eye-movement sleep were associated with worse performances on attention tests (p=0.03). Our findings indicate that more severe obstructive sleep apnea-related hypoxemia during sleep is associated with poorer cognitive performances on tests that assess attention/executive functions and verbal memory in patients with epilepsy. Overall, these results are consistent with the sleep apnea literature, and suggest that patients with epilepsy are also vulnerable to the effects of obstructive sleep apnea. Future prospective studies will help in determining whether treatment of obstructive sleep apnea may help improve cognitive functioning in patients with epilepsy.

Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level

Cognitive deficits are a major complaint in breast cancer patients, even before chemotherapy. Comprehension of the cerebral mechanisms related to cognitive impairment in breast cancer patients remains difficult due to the scarcity of studies investigating both cognitive and anatomical imaging changes. Furthermore, only some of the patients experienced cognitive decline following chemotherapy, yet few studies have identified risk factors for cognitive deficits in these patients. It has been shown that education level could impact cognitive abilities during the recovery phase following chemotherapy. Our main aim was to longitudinally evaluate cognitive and anatomical changes associated with cancer and chemotherapy in breast cancer patients. Our secondary aim was to assess the impact of education level on cognitive performances and gray matter (GM) atrophy in these patients. Twenty patients were included before chemotherapy (T1), 1month (T2) and 1year (T3) after chemotherapy. Twenty-seven controls without a history of cancer were assessed at T1 and T3 only. Cluster groups based on education level were defined for both groups and were further compared. Comparison between patients and controls revealed deficits in patients on verbal episodic memory retrieval at T1 and T3 and on executive functions at T3. After chemotherapy, breast cancer patients had GM atrophy that persisted or recovered 1year after chemotherapy depending on the cortical areas. Increase in GM volumes from T1 to T3 were also found in both groups. At T2, patients with a higher level of education compared to lower level exhibited higher episodic memory retrieval and state anxiety scores, both correlating with cerebellar volume. This higher level of education group exhibited hippocampal atrophy. Our results suggest that, before chemotherapy, cancer-related processes impact cognitive functioning and that this impact seems exacerbated by the effect of chemotherapy on certain brain regions. Increase in GM volumes after chemotherapy were unexpected and warrant further investigations. Higher education level was associated, 1month after the end of chemotherapy, with greater anxiety and hippocampal atrophy despite a lack of cognitive deficits. These results suggest, for the first time, the occurrence of compensation mechanisms that may be linked to cognitive reserve in relationship to state anxiety. This identification of factors, which may compensate cognitive impairment following chemotherapy, is critical for patient care and quality of life.

Prevalence and determinants of cognitive impairment in the euthymic phase of bipolar disorders: results from the FACE-BD cohort.

Cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, but risk factors associated with cognitive deficits in euthymic BD are still poorly understood. We aimed to validate classification criteria for the identification of clinically significant cognitive impairment, based on psychometric properties, to estimate the prevalence of neuropsychological deficits in euthymic BD, and identify risk factors for cognitive deficits using a multivariate approach. We investigated neuropsychological performance in 476 euthymic patients with BD recruited via the French network of BD expert centres. We used a battery of tests, assessing five domains of cognition. Five criteria for the identification of neuropsychological impairment were tested based on their convergent and concurrent validity. Uni- and multivariate logistic regressions between cognitive impairment and several clinical and demographic variables were performed to identify risk factors for neuropsychological impairment in BD. One cut-off had satisfactory psychometric properties and yielded a prevalence of 12.4% for cognitive deficits in euthymic BD. Antipsychotics use were associated with the presence of a cognitive deficit. This is the first study to validate a criterion for clinically significant cognitive impairment in BD. We report a lower prevalence of cognitive impairment than previous studies, which may have overestimated its prevalence. Patients with euthymic BD and cognitive impairment may benefit from cognitive remediation.

Cognitive and behavioral risk factors for child physical abuse among Chinese children: a multiple-informant study.

BackgroundIt has been well established that child physical abuse is a risk factor for cognitive deficits and behavioral problems. However, the possible link between cognitive deficits and behavioral problems placing children at a higher risk of physical abuse has been overlooked. Using a prospective design, the present study aims to examine whether previously measured cognition indicated by intelligence quotient (IQ), including performance IQ (PIQ) and verbal IQ (VIQ), and behavioral problems reported by multiple informants (i.e. mothers, teachers, and children) predict later child physical abuse (which may include minor and severe forms of abuse inflicted separately by mothers and fathers) in Chinese children.MethodsA school-based survey was conducted to collect data from 265 Chinese children (52.8 % boys, mean age 13.71 ± 0.60 years) in the Wave II of China Jintan Cohort study. When they were in the last year of elementary school, children completed the Chinese version of the Wechsler intelligence scale for children-revised that measured VIQ and PIQ during 2010–2012 when their behaviors were self-assessed. Mothers and teachers of these children used the Chinese versions of the youth self report, the child behavior checklist and the teacher report form, respectively, to assess the children’s behaviors. These children reported minor and severe physical abuse experiences in the previous 12 months from mothers and fathers separately using the Chinese version of parent–child conflict tactics scale in 2013 when children were in grades 7 and 8 of middle school.ResultsThe present study found that after controlling for the sociodemographic and other cognitive and/or behavior variables, high scores of child externalizing behavior rated by their mothers or teachers were associated with increased risks of experiencing maternal and paternal severe physical abuse, while a high score of self-reported externalizing behavior was associated with a decreased risk of paternal severe physical abuse. A high score of mother-rated internalizing behavior was associated with a decreased risk of maternal severe physical abuse. VIQ was associated with maternal minor physical abuse with small effect size. PIQ was not associated with any forms of physical abuse after adjusting for child behavior and sociodemographic variables.ConclusionsIn this community sample of Chinese children, externalizing behavior perceived by mothers and teachers is linked to children being at risk for physical abuse, while internalizing behavior perceived by mothers is associated with a decreased risk of maternal physical abuse. Findings suggest that educating parents and teachers to appropriately perceive children’s externalizing behavior may help prevent the occurrence of physical abuse.Electronic supplementary materialThe online version of this article (doi:10.1186/s13034-016-0124-5) contains supplementary material, which is available to authorized users.

Plasma soluble CD36, carotid intima-media thickness and cognitive function in patients with type 2 diabetes.

IntroductionDiabetes and atherosclerosis are both risk factors of cognitive deficits. Scavenger receptor CD36 is associated with increasing risk of diabetes and atherosclerosis, and may play a role in cognitive deficits. The aim of this study is to determine the correlations of plasma soluble CD36 concentrations with carotid intima-media thickness (IMT) and cognitive function in patients with type 2 diabetes.Material and methodsWe determined the levels of soluble CD36 (sCD36), blood lipids, fasting blood glucose, glycosylated hemoglobin, carotid atherosclerosis as IMT, cognitive function by the Montreal Cognitive Assessment (MoCA) scoring system, and other clinical characteristics in 357 patients with type 2 diabetes.ResultsDiabetic patients with the lowest quartile of IMT (Q1) had lower sCD36 concentrations (ANOVA, ptrend < 0.05) and higher MoCA scores than upper ones (Q2–Q4) (ptrend < 0.05), and those with the highest quartile of sCD36(Q4) had higher FBG, LDL-C and carotid IMT than lower ones (Q1–Q3) (ptrend < 0.05 for all). Plasma log10(sCD36) was significantly correlated with carotid IMT (r = 0.202, p < 0.001) after adjustment for age, gender, and education level. Carotid IMT was significantly associated with MoCA scores (r = 0.284, p < 0.001) after adjustment for, age, gender, education level, duration of DM and hypertension. There were no correlations between sCD36 and MoCA scores (r = –0.038, p = 0.470).ConclusionsOur study shows that sCD36 is associated with carotid IMT, and carotid IMT is inversely correlated with cognitive function in type 2 diabetic patients. Nevertheless, no cross-sectional association between sCD36 and MoCA scores was detected in this study.

Examining the effects of adjuvant chemotherapy on cognition and the impact of any cognitive impairment on quality of life in colorectal cancer patients: study protocol.

BackgroundResearch suggests that chemotherapy can cause deficits in both patients’ objectively measured and self-reported cognitive abilities which can in turn affect their quality of life (QoL). The majority of research studies have used post-treatment retrospective designs or have not included a control group in prospective cohorts. This has limited the conclusions that can be drawn from the results. There have also been a disproportionate number of studies focussed on women with breast cancer, which has limited the generalisability of the results to other cancer populations.AimThis study aims to identify the extent and impact of chemotherapy-induced cognitive decline in colorectal cancer patients. Possible associations with poorer QoL will also be explored.DesignThis will be a longitudinal controlled cohort study. Questionnaires measuring subjective cognitive functioning, QoL, fatigue and mood, and neuropsychological assessments of objective cognitive function will be collected pre-, mid- and post- chemotherapy treatment from a consecutive sample of 78 colorectal cancer patients from five London NHS Trusts. A further 78 colorectal cancer surgery only patients will be assessed at equivalent time points; this will allow the researchers to compare the results of patients undergoing surgery, but not chemotherapy against those receiving both treatments.Pre- and post-chemotherapy difference scores will be calculated to detect subtle changes in cognitive function as measured by the objective neuropsychological assessments and the self-reported questionnaires. A standardised z-score will be computed for every patient on each neuropsychological test, and for each test at each time point. The post-chemotherapy score will then be subtracted from the pre-chemotherapy score to produce a relative difference score for each patient.ANCOVA will be used to compare mean difference z-scores between the chemotherapy and surgery-only groups while controlling for the effects of gender, age, depression, anxiety, fatigue and education.DiscussionThe result from this study will indicate whether a decline in cognitive functioning can be attributed to chemotherapy or to disease, surgical or some other confounding factor. Identification of risk factors for cognitive deficits may be used to inform targeted interventions, in order to improve QoL and help patients’ cope.

Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24months) and young (4months) male Wistar rats were intracerebroventricularly injected with insulin (20mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-β, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

Performance of a computer‐based assessment of cognitive function measures in two cohorts of seniors

Computer-administered assessment of cognitive function is being increasingly incorporated in clinical trials; however, its performance in these settings has not been systematically evaluated. The Seniors Health and Activity Research Program pilot trial (N = 73) developed a computer-based tool for assessing memory performance and executive functioning. The Lifestyle Interventions and Independence for Elders investigators incorporated this battery in a full-scale multicenter clinical trial (N = 1635). We describe relationships that test scores have with those from interviewer-administered cognitive function tests and risk factors for cognitive deficits and describe performance measures (completeness, intraclass correlations [ICC]). Computer-based assessments of cognitive function had consistent relationships across the pilot and full-scale trial cohorts with interviewer-administered assessments of cognitive function, age, and a measure of physical function. In the Lifestyle Interventions and Independence for Elders cohort, their external validity was further demonstrated by associations with other risk factors for cognitive dysfunction: education, hypertension, diabetes, and physical function. Acceptable levels of data completeness (>83%) were achieved on all computer-based measures; however, rates of missing data were higher among older participants (odds ratio = 1.06 for each additional year; p < 0.001) and those who reported no current computer use (odds ratio = 2.71; p < 0.001). ICCs among clinics were at least as low (ICC < 0.013) as for interviewer measures (ICC < 0.023), reflecting good standardization. All cognitive measures loaded onto the first principal component (global cognitive function), which accounted for 40% of the overall variance. Our results support the use of computer-based tools for assessing cognitive function in multicenter clinical trials of older individuals.

Influence of Type 2 Diabetes on Brain Volumes and Changes in Brain Volumes

OBJECTIVETo study how type 2 diabetes adversely affects brain volumes, changes in volume, and cognitive function.RESEARCH DESIGN AND METHODSRegional brain volumes and ischemic lesion volumes in 1,366 women, aged 72–89 years, were measured with structural brain magnetic resonance imaging (MRI). Repeat scans were collected an average of 4.7 years later in 698 women. Cross-sectional differences and changes with time between women with and without diabetes were compared. Relationships that cognitive function test scores had with these measures and diabetes were examined.RESULTSThe 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01) but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in gray matter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits.CONCLUSIONSDiabetes is associated with smaller brain volumes in gray but not white matter and increasing ischemic lesion volumes throughout the brain. These markers are associated with but do not fully account for diabetes-related deficits in cognitive function.

Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults

The objective of the study was to asses the possible influence of hypothalamo-pituitary deficiencies, and growth hormone (GH) deficiency in particular, on cognition in adult patients with traumatic brain injury (TBI). TBI is a recently identified risk factor for cognitive deficits and hypopituitarism. Even the patients with favorable outcome after TBI may present with persistent bodily, psychosocial, and cognitive impairments, resembling patients with untreated partial or complete pituitary insufficiency. We performed retrospective and cross-sectional study of endocrine and cognitive function in TBI in 61 patients (aged 37.7 +/- 1.7 years) of both sexes (44 m,17 f), at least 1 year after TBI (3.9 +/- 0.6 years). Serum insulin-like growth factor 1 (IGF-I), thyroxin, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (in men), prolactin, and cortisol were measured, and GH secretion was assessed by growth hormone releasing hormone (GHRH) + growth hormone releasing peptide-6 (GHRP-6) test. Cognitive function was assessed by using a standard neuropsychological battery. GH deficiency (GHD) and GH insufficiency (GHI) were found in 20 patients (32.8%). After adjustment for confounders [age, body mass index (BMI), education level, time elapsed from TBI], there were no significant differences in results of neuropsychological tests between patients with TBI with GHD, GHI, and normal GH secretion. There were no correlations of neuropsychological variables with stimulated peak GH secretion or IGF-I level. GHD persists long after the TBI, independently of trauma severity and age at traumatic event. GH secretion is more sensitive to TBI than other pituitary hormones. No evidence is found for an association of cognitive function impairment and somatotropic axis impairment in adult patients tested more than 1 year after the TBI.

Teaching the Teachers: Data to Benefit School Systems and Doctors about Children with Newly Diagnosed Epilepsy

Neuropsychological Status at Seizure Onset in Children: Risk Factors for Early Cognitive Deficits. Fastenau PS, Johnson CS, Perkins SM, Byars AW, deGrauw TJ, Austin JK, Dunn DW. Neurology 2009;73(7):526–534. OBJECTIVE: This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for cognitive deficits. METHODS: We compared 282 children (ages 6–14 years, IQ ≥ 70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables. RESULTS: In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio [OR] = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00). CONCLUSIONS: A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition.

Sex Differences in High‐fat Diet‐induced Obesity, Metabolic Alterations and Learning, and Synaptic Plasticity Deficits in Mice

Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9-12 months) gained significantly more weights than the sex-specific control groups. Compared with the obese female mice, the obese males had similar energy intake but developed more weight gains. The obese male mice developed hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia, but not hypertriglyceridemia. The obese females had less hyperinsulinemia and hypercholesterolemia than the obese males, and no hyperglycemia and hypertriglyceridemia. In the contextual fear conditioning and step-down passive avoidance tasks, the obese male, but not female, mice showed poorer learning performance than their normal counterparts. These learning deficits were not due to sensorimotor impairment as verified by the open-field and hot-plate tests. Although, basal synaptic transmission characteristics (input-output transfer and paired-pulse facilitation (PPF) ratio) were not significantly different between normal and HFD groups, the magnitudes of synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)) were lower at the Schaffer collateral-CA1 synapses of the hippocampal slices isolated from the obese male, but not female, mice, as compared with their sex-specific controls. Our results suggest that male mice are more vulnerable than the females to the impacts of HFD on weight gains, metabolic alterations and deficits of learning, and hippocampal synaptic plasticity.

Neuropsychological status at seizure onset in children

This large, prospective, community-based study characterized neuropsychological functioning and academic achievement at the time of the first recognized seizure and identified risk factors for cognitive deficits. We compared 282 children (ages 6-14 years, IQ > or =70) with a first recognized seizure to 147 healthy siblings on a battery of well-standardized and widely used neuropsychological and academic achievement tests and examined relationships with demographic and clinical variables. In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychological deficits at or near onset. Risk factors associated with neuropsychological deficits included multiple seizures (i.e., second unprovoked seizure; odds ratio [OR] = 1.96), use of antiepileptic drugs (OR = 2.27), symptomatic/cryptogenic etiology (OR = 2.15), and epileptiform activity on the initial EEG (OR = 1.90); a child with all 4 risks is 3.00 times more likely than healthy siblings to experience neuropsychological deficits by the first clinic visit. Absence epilepsy carried increased odds for neuropsychological impairment (OR = 2.00). A subgroup of intellectually normal children with seizures showed neuropsychological deficits at onset. Academic achievement was unaffected, suggesting that there is a window early in the disorder for intervention to ameliorate the impact on school performance. Therefore, the risk factors identified here (especially if multiple risks are present) warrant swift referral for neuropsychological evaluation early in the course of the condition.

The effect of maternal smoking during pregnancy on intellectual disabilities among 8‐year‐old children

Prenatal tobacco smoke exposure has been implicated as a risk factor for cognitive deficits in children. The purpose of this study is to examine the association between prenatal tobacco smoke exposure and diagnosis of intellectual disabilities (ID) among 8-year-old children living in Arkansas, Georgia, North Carolina and Utah. In 2002 and 2004, 965 ID case children were identified through a surveillance network and compared with the population of children born in the surveillance region during the same period (n = 104 607). Prenatal tobacco smoke exposure was determined from birth certificates. We estimated the effect of prenatal tobacco smoke exposure (none, <10, 10-19 and > or =20 cigarettes per day) on ID using logistic regression. Generally, the risk of ID was mildly elevated among children whose mothers smoked > or =20 cigarettes per day during pregnancy [RR 1.34; 95% (confidence interval) CI 0.96, 1.87] after adjustment for maternal education, maternal race, maternal age, marital status, child sex, birth year and study site. However, the effect of exposure to > or =20 cigarettes per day significantly differed for males [RR 1.77, 95% CI 1.20, 2.62] compared with females [RR 0.81, 95% CI 0.44, 1.50]. Supplemental analyses reveal substantial confounding of this relationship by socio-economic indicators. A differential effect of tobacco smoke exposure on the risk of ID is suggested for males and females and deserves further investigation; however, the interpretation is tempered by the potential for residual confounding.