Decrements In Cognitive Function Research Articles

Negative Association of Cognitive Performance With Blood Serum Neurotoxicity and Its Modulation by Human Herpes Virus 5 (HHV5) Seropositivity in Healthy Women.

Identification of early influences on cognitive decline is of paramount importance in order to stem the impacts of decrements in cognitive functioning and to potentially intervene. Thus, here we focused on 132 healthy adult women (age range 26-98 years) to (a) determine whether factors circulating in serum may exert neurotoxic effects in vitro, (b) evaluate associations between serum neurotoxicity and cognitive performance, and (c) assess the influence of human herpes virus (HHV) seroprevalence and other factors on apoptosis and cognitive performance. The results documented that the addition of serum from healthy adult women to neural cell cultures resulted in apoptosis, indicating the presence of circulating neurotoxic factors in the serum. Furthermore, apoptosis increased with age, and was associated with decreased cognitive performance. Stepwise regression evaluating the influence of 6 HHVs on apoptosis and cognitive function revealed that only HHV5 (cytomegalovirus; CMV) seropositivity was significantly associated with apoptosis and cognitive decline, controlling for age. These findings document neurotoxic effects of serum from healthy women across the adult lifespan and suggest a unique detrimental influence associated with CMV seropositivity.

Dependence of cognitive ability on synchronous neural interactions determined by magnetoencephalography.

Previous studies have shown that synchronous neural interactions (SNIs) underlying healthy brain function can be readily distinguished from neural anomalies associated with diseases including dementia; however, it is imperative to identify biomarkers that facilitate early identification of individuals at risk for cognitive decline before the onset of clinical symptoms. Here, we evaluated whether variation in brain function, controlling for age, corresponds with subtle decrements in cognitive performance in cognitively healthy women. A total of 251 women (age range 24-102 yr) who performed above established cutoffs on the Montreal cognitive assessment (MoCA) also underwent a task-free magnetoencephalography scan from which SNIs were computed. The results demonstrated that increased SNI was significantly associated with decreased cognitive performance (r2 = 0.923, P = 0.009), controlling for age. Compared with the lowest performers with normal cognition (MoCA = 26), SNI of the highest performers (MoCA = 30) was associated with decorrelation primarily in the right anterior temporal cortex region, with additional (weaker) foci in left anterior temporal cortex, right posterior temporal cortex, and cerebellum. The findings highlight the relevance of neural network decorrelation on cognitive functioning and suggest that subtle increases in SNI may presage future cognitive impairment.NEW & NOTEWORTHY This study in cognitively healthy women showed that decreased cognitive performance is associated with increased neural network correlations, particularly involving the temporal cortices. As healthy brain function relies on dynamic neural network communication, these findings suggest that subtle increases in correlated neural network activity may be a useful early indicator of decrements in cognitive function.

Changes in Subjective Measures of Cognitive Function in Older Adults From the Initiation Through 12 Months After the Receipt of Chemotherapy.

Cognitive impairment has a negative impact on older patients with cancer. The aim of this study was to evaluate for interindividual differences in 2 subjective measures of cognitive function in older patients (n = 112), as well as determine which demographic, clinical, and symptom characteristics, and levels of physical function, were associated with initial levels and with the trajectory of each of these 2 measures. Cognitive function was assessed using the cognitive function scale from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the Attentional Function Index at the initiation of chemotherapy and at 1, 3, 6, 9, and 12 months after its initiation. Hierarchical linear modeling was used to assess for interindividual differences in and characteristics associated with initial levels and changes in cognitive function. Characteristics associated with decreases in Quality of Life Questionnaire Core 30 scores at the initiation of chemotherapy were longer time since the cancer diagnosis and higher depression scores. Characteristics associated with poorer Attentional Function Index scores at enrollment were lower levels of education and higher depression scores. No characteristics were associated with worse trajectories of either cognitive function measure. Some older patients undergoing chemotherapy experience decrements in cognitive function. Our findings suggest that clinicians need to assess for depressive symptoms in older patients before the initiation of chemotherapy. Evidence-based interventions (eg, cognitive stimulation, increased physical activity) can be recommended to maintain and increase cognitive function in older oncology patients.

Associations Between Cognitive Functioning and Mortality in a Population-Based Sample of Older United States Adults: Differences by Sex and Education.

Objective: To determine whether cognition is associated with mortality among older US adults. Methods: We studied 5,989 National Health and Nutrition Examination Survey participants age 60+ in years 1999-2014 with mortality follow-up through 2015. Cognitive function was measured in one standard deviation decrements using the Digit Symbol Substitution Test (DSST), Animal Fluency (AnFl), and two Consortium to Establish a Registry for Alzheimer's Disease (CERAD) tests. Results: Each decrement in cognitive function was associated with increased risk of mortality overall (DSST HR: 1.36, 95% CI: 1.25, 1.48), among women only (AnFl: 1.51, 95% CI: 1.02, 2.24), and among those with less than a high school education only (AnFl HR: 1.46, 95% CI: 1.09, 1.97; CERAD-WL HR: 1.34, 95% CI: 1.07, 1.67; and CERAD-DR HR: 1.38, 95% CI: 1.05, 1.82). Discussion: Among US adults, lower cognitive functioning was associated with mortality; associations were stronger among women and those with less education.

The relationship of carotid artery disease with mental and neurocognitive disorders

Carotid stenosis constitutes a common vascular disease that significantly affects cerebral blood flow and thus is associated with patients' cognitive functions. Carotid revascularization techniques [carotid endarterectomy (CEA) and carotid artery stenting (CAS)] may benefit cognition, though there are opposing findings, reporting an apparent decrement in cognitive function, no effect, or an apparent improvement after revascularization. A great number of studies are trying to evaluate the effect of carotid revascularization (CEA, CAS) on patients' cognitive functions, as well as on their psychological condition and quality of life through a baseline and follow-up neuropsychological examination. Recent reviews refer only to the narrow limits of cognitive deficits that may be attributed to carotid stenosis, rather than elucidating the outfit of all aspects of mental and cognitive correlations. Most of those findings depict controversy in current literature as far as the neuropsychological effects of carotid revascularization techniques are concerned, while clinical entities of "vascular dementia" and "vascular depression", as well as intercurrent vascular risk factors are also addressed. This might be taken into consideration, when determining the optimal therapeutic strategy for tackling carotid artery occlusive disease, while best practice clinical decisions should be still focused on stroke prevention and symptoms alleviation, until further research on the field of neuroangiology presents undisputable conclusions regarding the underlying effects of revascularization on mood and cognition. Τhe neurovascular interface, as far as mental and neurocognitive impact of carotid stenosis is concerned, also, comprises, the conceptual pathophysiological entity of "atheroinflammation", underscoring the association of vascular lesions with cognitive impairment, major depressive disorder and bipolar disorder. Chronic recurrent ischemia and chronic low perfusion are also addressed from neurocognitive aspect, regarding therapeutic strategies that might be preferred so as to reduce the burden of chronic cerebrovascular disease in both symptomatic and asymptomatic patients, given the fact that inflammatory processes of vascular complexion underlie both neuroinflammation and atherosclerosis, affecting cerebral perfusion as well as cortical blood flow.

Aberrant inhibitory processing in the somatosensory cortices of cannabis-users

Delta-9 tetrahydrocannabinol (THC) is a major exogenous psychoactive agent, which acts as a partial agonist on cannabinoid (CB1) receptors. THC is known to inhibit presynaptic neurotransmission and has been repeatedly linked to acute decrements in cognitive function across multiple domains. Previous electrophysiological studies of sensory gating have shown specific deficits in inhibitory processing in cannabis-users, but to date these findings have been limited to the auditory cortices, and the degree to which these aberrations extend to other brain regions remains largely unknown. We used magnetoencephalography (MEG) and a paired-pulse somatosensory stimulation paradigm to probe inhibitory processing in 29 cannabis-users (i.e. at least four times per month) and 41 demographically matched non-user controls. MEG responses to each stimulation were imaged in both the oscillatory and time domain, and voxel time-series data were extracted to quantify the dynamics of sensory gating, oscillatory gamma activity, evoked responses, and spontaneous neural activity. We observed robust somatosensory responses following both stimulations, which were used to compute sensory gating ratios. Cannabis-users exhibited significantly impaired gating relative to non-users in somatosensory cortices, as well as decreased spontaneous neural activity. In contrast, oscillatory gamma activity did not appear to be affected by cannabis use. We observed impaired gating of redundant somatosensory information and altered spontaneous activity in the same cortical tissue in cannabis-users compared to non-users. These data suggest that cannabis use is associated with a decline in the brain's ability to properly filter repetitive information and impairments in cortical inhibitory processing.

Impact Of Higher Aerobic Fitness On Neurocognitive Function During Simulated Military Operational Stress

Modern warfare involves a greater reliance on executive functions such as memory, recognition, and reasoning. Greater aerobic fitness has been associated with minimizing decrements in cognitive function during physical stress scenarios. PURPOSE: To determine the effect of aerobic fitness on higher order neurocognitive function during simulated military operational stress (SMOS). METHODS: Fifty-four male service members (SMs) (age: 26.4 ± 5.4 years, height: 177.9 ± 6.5 cm, weight: 85.2 ± 14.0 kg) took part in the 5 day/night protocol. After a day of familiarization testing (D0) including a treadmill VO2peak test, SMs completed one day of baseline testing (D1). On D2 and D3, sleep was restricted to 0100-0300 and 0500-0700 and SMs were allotted 50% of caloric needs based on estimated total energy expenditure. SMs were permitted to sleep from 2300-0700 and received 100% of their caloric needs all other days. Each afternoon after completion of a physical testing battery, SMs completed a neurocognitive test battery: Reading the Mind in the Eyes (RME) to measure emotional recognition, Match to Sample (MATCH) to assess short-term spatial memory, and Grammatical Reasoning (GRAM) to evaluate language-based logical reasoning. SMs were split into aerobic fitness tertiles based on VO2peak (LOW: < 45.0; MOD: 45.0-51.54; HIGH: > 51.54 mL·kg·min-1). Two-way mixed ANOVA and Bonferroni correction for multiple comparisons were used to analyze group*day interaction on average reaction time (RT) and accuracy (ACC) for MATCH and GRAM, as well as RME ACC, across D1, D3, and D4 of the SMOS. RESULTS: There were no significant group*day interaction effects. However, a significant main effect of group was observed in both MATCH ACC (p = 0.023, ηp2 = 0.145) and GRAM ACC (p = 0.032, ηp2 = 0.131). On average, HIGH SMs exhibited 20% higher MATCH ACC (p = 0.046) and 25% higher GRAM ACC (p = 0.036) scores compared to LOW SMs. A main effect of time indicated MATCH (p < 0.001, ηp2 = 0.263) and GRAM (p < 0.001, ηp2 = 0.290) RT decreased throughout the SMOS. RME remained stable through the 5-day protocol. CONCLUSION: SMs with high aerobic fitness performed better at logical reasoning and spatial memory tasks. Increased aerobic fitness is influential to maintaining cognitive functions in response to the physical and cognitive stress observed in military operations.

Maternal methylmercury exposure through rice ingestion and child neurodevelopment in the first three years: a prospective cohort study in rural China

BackgroundRice is an important dietary source for methylmercury; however, rice does not contain the same beneficial nutrients as fish. Our main objective was to assess associations of prenatal methylmercury exposure through rice ingestion with child neurodevelopment in rural China.MethodsEligible peripartum women were enrolled (n = 391), provided peripartum hair samples, and children’s neurodevelopment was assessed at 12 months (n = 264, 68%) and 36 months (n = 190, 48%) using the Bayley Scales of Infant Development, 2nd Edition, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). Associations between prenatal methylmercury exposure during the third trimester [log2 maternal hair total mercury (THg)] and child’s neurodevelopment were assessed using linear mixed models for repeated measures.ResultsIn adjusted models, a doubling in maternal hair THg corresponded to a 1.3-point decrement in the MDI score [95% confidence interval (CI): − 2.6, − 0.14], and a 1.2-point decrement in the PDI score (95% CI: − 2.6, 0.14). Overall, adverse associations between maternal hair THg and MDI scores attenuated over time. However, associations were robust and stable over time among children whose primary caregiver was their parent(s). During the study follow-up, an increasing proportion of children were raised by grandparents (12 months: 9% versus 36 months: 27%), a trend associated with rural-to-urban parental migration for work.ConclusionsFor young children living in rural China, a biomarker of prenatal methylmercury exposure was associated with decrements in cognitive function assessed between 12 and 36 months of age. Changes in the family structure over the study follow-up time interval potentially impacted children’s sensitivity to prenatal methylmercury exposure.

Aberrant Inhibitory Processing in the Somatosensory Cortices of Cannabis Users

Delta-9 tetrahydrocannabinol (THC) is a major exogenous psychoactive agent, which acts as a partial agonist on cannabinoid (CB1) receptors. THC is known to inhibit presynaptic neurotransmission and has been repeatedly linked to acute decrements in cognitive function across multiple domains. Previous electrophysiological studies of sensory gating have shown specific deficits in inhibitory processing in cannabis users, but to date, these findings have been limited to the auditory cortices and the degree to which these aberrations extend to other brain regions remains largely unknown.

Cognitive Impairment, Meditative Movement, and Gene Expression in Breast Cancer Survivors

Breast cancer survivors (BCSs) report decrements in cognitive functioning. A Meditative Movement (MM) program (Qigong/Tai Chi Easy) combines meditation and exercise, practices known to improve cognitive function. Method: Using a single group, pre- to post-intervention assessment design, a pilot study was conducted in BCSs to test the effects of an 8-week MM intervention on cognitive functioning, sleep and mood and to explore changes on selected gene expression factors, BDNF, NF-kB1, and TP53, expected to improve with symptoms. BCSs (n=14; mean age = 61) completed the MM intervention, provided blood samples and answered questionnaires assessing cognitive function using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-COG) and the Wechsler Adult Intelligence Scale (WAIS-III). Sleep and mood were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Profile of Mood States (POMS) subscales for anxiety and depression. Results: Significant improvements were noted in the FACT-COG subscales: Perceived Cognitive Impairments (p = .01), Perceived Cognitive Abilities (p = .03), Perceived Impairments on Quality of Life (p = .04), and Comments from Others (p = .04). The WAIS-III results indicated a significant improvement in Letter-Number sequencing (p-value = .01), but not for Digit Span Forward/Backwards (p-value = .60). The PSQI (p = .03) and the POMS/anxiety subscale (p = .05) showed a significant decrease. Significant changes in POMS/depression, BDNF, NF-kB1, and TP53 were not found. The intervention was shown to improve cognitive functioning, sleep quality and anxiety suggesting that MM may contribute to the recovery of a subset of persistent symptoms among BCSs.

Depression and Cognitive Dysfunction in Older U.S. Military Veterans: Moderating Effects of BDNF Val66Met Polymorphism and Physical Exercise

ObjectiveDepression is associated with increased risk for cognitive dysfunction, yet little is known about genetic and behavioral factors that may moderate this association. Using data from a nationally representative sample of older U.S. military veterans, we examined the direct and interactive effects of depression, brain-derived neurotropic factor (BDNF) Val66Met genotype, and physical exercise on cognitive functioning. MethodsOne thousand three hundred eighty-six older European-American U.S. military veterans (mean age = 63) completed a web-based survey and cognitive assessment. Analyses of covariance were conducted to evaluate the effects of depression, BDNF Met allele carrier status, and physical exercise on these measures. ResultsDepressed veterans scored worse than nondepressed veterans on subjective measures of cognitive functioning (Cohen d's = 0.34–0.57) and objective measures of visual learning (d = 0.39) and working memory (d = 0.28). Among depressed veterans, those who were Met allele carriers scored worse than Val/Val homozygotes on subjective cognitive measures (d's = 0.52–0.97) and an objective measure of visual learning (d = 0.36). Engagement in physical exercise moderated the association between depression and cognitive function, with depressed exercisers scoring better than depressed nonexercisers on a subjective measure of reasoning, and objective measures of processing speed, attention, and visual learning (d = 0.58–0.99): further, in depressed Met allele carriers, exercisers scored better than nonexercisers on subjective cognitive (d's = 0.80–1.92), and objective measures of visual learning (d = 0.8–1.31) and working memory (d = 0.67). ConclusionDepression is associated with moderate decrements in cognitive functioning in older U.S. military veterans, and this association is moderated by BDNF Val66Met genotype and physical exercise. Prevention and treatment efforts designed to promote physical exercise may help preserve cognitive functioning in at-risk veterans.

Acute Exercise Impairs Cognitive Function at High Altitude

Ascent to high altitude can impair aspects of cognitive function in an altitude‐dependent manner. Interestingly, a single bout of aerobic exercise transiently improves cognitive function in normobaric hypoxia, suggesting that aerobic exercise may be an effective strategy for improving brain function at altitude, but this phenomenon has yet to be explored. The purpose of this study was to investigate the effect of a single bout of aerobic exercise on cognitive function at low and high altitude in the Nepal Himalaya. Fifteen healthy volunteers (24.1±3.5yrs; 9 females) performed 20 minutes of aerobic exercise at 40–60% of their heart rate (HR) reserve at low (1400m) and high altitude (4370m) after 7 days of incremental ascent. Ascent‐related physiological data were collected in the morning before exercise including arterial blood pressure, HR, peripheral capillary oxygen saturation, hemoglobin concentration, hematocrit, end‐tidal CO2 (PETCO2), and acute mountain sickness (AMS) scores. During exercise, participants wore HR monitors in order to maintain HR within the prescribed intensity zone. Cognitive function was assessed before and 10‐min after exercise using a battery of standardized iPad‐based tests (BrainBaseline, Digital Artefacts). A 2‐factor (Time × Condition) repeated measures analysis of variance was performed to examine differences in cognitive function before and after exercise (Time) at low and high altitude (Condition). Exploratory correlations were performed to investigate the relationship between changes in physiological measures with high‐altitude ascent and during exercise and changes in cognitive function. There was a significant interaction between altitude and exercise on a test of processing speed, working memory, and visuospatial attention, such that performance worsened following exercise at high altitude (P=0.02). In contrast, task‐switching abilities and inhibitory control remained unchanged after exercise. Higher baseline hemoglobin was associated with a decline in cognitive performance following exercise at high altitude (r= −0.58, P=0.01), whereas higher baseline PETCO2 was associated with improved cognitive performance following exercise at high altitude (r=0.54, P=0.03). Interestingly, there was no relationship between AMS scores and changes in cognitive function. In conclusion, acute aerobic exercise performed at high altitude impairs some measures of cognitive function, which may be impacted by physiological acclimatization during ascent. Future work should investigate the persistence of this post‐exercise decrement in cognitive function to help inform recommendations regarding decision‐making behaviors following exercise at high‐altitude.Support or Funding InformationNSERC Discovery, NSERC PGS, and Wilderness Medical Society Research In‐Training AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Strength and Temporal Variance of the Default Mode Network to Investigate Chronic Mild Traumatic Brain Injury in Service Members with Psychological Trauma.

Background:There is a significant number of military personnel with a history of mild traumatic brain injury (mTBI) who suffer from comorbid posttraumatic stress symptoms (PTS). Although there is evidence of disruptions of the default mode network (DMN) associated with PTS and mTBI, previous studies have only studied static connectivity while ignoring temporal variability of connectivity.Objective:To assess DMN disrupted or dysregulated neurocircuitry, cognitive functioning, and psychological health of active-duty military with mTBI and PTS.Method:U.S. Army soldiers with PTS (n = 14), mTBI + PTS (n = 25), and healthy controls (n = 21) voluntarily completed a cognitive and symptom battery. In addition, participants had magnetic resonance imaging (MRI) to assess both static functional connectivity (SFC) and variance of dynamic functional connectivity (vDFC) of the DMN.Results:Both the PTS and mTBI + PTS groups had significant symptoms, but only the comorbid group had significant decrements in cognitive functioning. Both groups showed less stable and disrupted neural signatures of the DMN, mainly constituting the cingulate-frontal-temporal-parietal attention network. Specifically, the PTS group showed a combination of both reduced contralateral strength and reduced unilateral variability of frontal-cingulate-temporal connectivities, as well as increased variability of frontal-parietal connectivities. The mTBI + PTS group had fewer abnormal connectives than the PTS group, all of which included reduced strength of frontal-temporal regions and reduced variability frontal-cingulate-temporal regions. Greater SFC and vDFC connectivity of the left dorsolateral prefrontal cortex (dlPFC) ↔ precuneus was associated with higher cognitive scores and lower symptom scores.Conclusions:Findings suggest that individuals with PTS and mTBI + PTS have a propensity for accentuated generation of thoughts, feelings, sensations, and/or images while in a resting state. Compared with controls, only the PTS group was associated with accentuated variability of the frontal-parietal attention network. While there were no significant differences in DMN connectivity strength between the mTBI + PTS and PTS groups, variability of connectivity was able to distinguish them.

Influence of Concussion History and Genetics on Event-Related Potentials in Athletes: Potential Use in Concussion Management.

Sports-related concussions are an increasing public health issue with much concern about the possible long-term decrements in cognitive function and quality of life that may occur in athletes. The measurement of cognitive function is a common component of concussion management protocols due to cognitive impairments that occur after sustaining a concussion; however, the tools that are often used may not be sensitive enough to expose long term problems with cognitive function. The current paper is a brief review, which suggests that measuring cognitive processing through the use of event related potentials (ERPs) may provide a more sensitive assessment of cognitive function, as shown through recent research showing concussion history to influence ERPs components. The potential influence of genetics on cognitive function and ERPs components will also be discussed in relation to future concussion management.

The Femininity–Money Incongruity Hypothesis

Women are often stereotyped as poorly equipped to deal with money matters, compared to men, yet very little research has examined the underpinnings and consequences of such gender stereotypes. Drawing on descriptive and prescriptive elements of women’s social roles, we empirically examined the gendered nature of money stereotypes. Specifically in the current work, we introduced and investigated the femininity–money incongruity hypothesis, which suggests that when the concepts of femininity and money are both cognitively activated, money will become a liability for women, causing decrements in cognitive functioning. We first probed the role of gender identity and benevolent sexism beliefs in women’s endorsement of money–gender stereotypes. In two subsequent experiments, we tested the hypothesis that simultaneously activating money and femininity would lead to decrements in cognitive functioning. Converging results across studies suggest that money is incompatible with the stereotypic female gender identity, and this incongruity has detrimental cognitive costs for women as they navigate gender roles. Implications of societal challenges imposed on women by gender stereotypes regarding money matters at work and in relationship contexts and proposed interventions are discussed. Additional online materials for this article are available on PWQ’s website at http://journals.sagepub.com/doi/suppl/10.1177/0361684317718505

Circulating progenitor cells are positively associated with cognitive function among overweight/obese children

Recent evidence has indicated that overweight/obese children may experience cognitive and immune dysfunction, but the underlying mechanisms responsible for the association between overweight/obesity, immune dysfunction, and cognition have yet to be established. The present study aimed to identify a novel link between obesity-induced immune system dysregulation and cognition in preadolescent children. A total of 27 male children (age: 8–10years) were recruited and separated by body mass index (BMI) into healthy weight (HW: 5th–84.9th percentile, n=16) and overweight/obese (OW: ⩾85th percentile, n=11) groups. Adiposity was assessed using dual energy X-ray absorptiometry (DXA), and aspects of executive function were assessed using the Woodcock-Johnson III Tests of Cognitive Abilities. Monocyte populations (CD14+CD16−, CD14+CD16+) with and without expression of chemokine receptor type 2 (CCR2), and circulating progenitor cells (CPCs: CD34+CD45dim), in peripheral blood were quantified by flow cytometry. CPCs were isolated by flow sorting and cultured for 24h for collection of conditioned media (CM) that was applied to SH-SY5Y neuroblastomas to examine the paracrine effects of CPCs on neurogenesis. OW had significantly higher quantities of both populations of monocytes (CD14+CD16−: 57% increase; CD14+CD16+: 95% increase, both p<0.01), monocytes expressing CCR2 (CD14+CD16−CCR2+: 66% increase; CD14+CD16+CCR2+: 168% increase, both p<0.01), and CPCs (47% increase, p<0.05) than HW. CPCs were positively correlated with abdominal adiposity in OW, and negatively correlated in HW with a significant difference between correlations (p<0.05). CPC content was positively correlated with executive processes in OW, and negatively correlated in HW with a significant difference in the strength of the correlations between groups (p<0.05 for correlation between OW and HW). Finally, CPC-CM from OW trended to increase neuroblast viability in vitro relative to HW (1.79 fold, p=0.07). These novel findings indicate that increased content of CPCs among OW children may play a role in preventing decrements in cognitive function via paracrine mechanisms.

Metabolism in the Diabetic Brain: Neurochemical Profiling by 1H Magnetic Resonance Spectroscopy

Diabetes is associated with decrements in cognitive function and with abnormalities in brain morphology. In addition, alterations of metabolism have been reported in the diabetic brain. Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique that can be employed to determine the concentration of metabolites in a fully non-invasive manner under normal physiological conditions. The present article reviews major findings from 1H MRS studies in the brain of diabetes patients, and of pre-clinical models of both insulin-dependent and insulin-resistant diabetes. Metabolic alterations measured in vivo by MRS are closely associated to events of the neurodegenerative process at cellular level, and thus allow understanding the pathophysiology of diabetes-associated brain complications. Moreover, MRS constitutes an excellent tool for tracking outcomes of therapeutic interventions. However, further studies are required to clearly establish the links between diabetes-induced alterations of metabolism, structure and function in the brain.

Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes.

To ascertain whether hypoglycemia in association with sleep deprivation causes greater cognitive dysfunction than hypoglycemia alone and protracts cognitive recovery after normoglycemia is restored. Fourteen adults with type 1 diabetes underwent a hyperinsulinemic, hypoglycemic clamp on two separate occasions. Before one glucose clamp, the participants stayed awake overnight to induce sleep deprivation. Participants were randomized and counterbalanced to the experimental condition. Cognitive function tests were performed before and during hypoglycemia and for 90 min after restoration of normoglycemia. Cognitive impairment during hypoglycemia did not differ significantly between the sleep-deprived and non-sleep-deprived conditions. However, in the sleep-deprived state, digit symbol substitution scores and choice reaction times were significantly poorer during recovery (P < 0.001) and hypoglycemia symptom scores were significantly higher (P < 0.001), even when symptoms that may have been caused by sleep deprivation, such as tiredness, were removed. Hypoglycemia per se produced a significant decrement in cognitive function; coexisting sleep deprivation did not have an additive effect. However, after restoration of normoglycemia, preceding sleep deprivation was associated with persistence of hypoglycemic symptoms and greater and more prolonged cognitive dysfunction during the recovery period.

Longitudinal Evaluation of Cognitive Functioning in Young Children with Type 1 Diabetes over 18 Months.

Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.

Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin

Recent evidence suggests that inflammation-induced decrements in cognitive function can be mitigated via manipulation of excitatory or inhibitory transmission. We tested the ability of the inverse benzodiazepine agonist, MRK-016 (MRK) to protect against LPS-induced deficits in memory acquisition and consolidation, using a contextual fear conditioning (CFC) paradigm. In Experiment One, mice received lipopolysaccharide (LPS) and/or MRK injections prior to CFC training, and were then tested 24h after training. In Experiment Two, animals received similar treatment injections immediately after training, and were tested 24h later. Additionally, hippocampal samples were collected 4h after LPS injections and immediately after testing, to evaluate brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) mRNA expression. Results indicate that MRK can protect against LPS-induced learning/memory decrements in both paradigms. We also found, in both paradigms, that animals treated with LPS/Saline expressed significantly less BDNF mRNA when compared to Saline/Saline-treated animals 4h after LPS administration, but that MRK did not restore BDNF expression levels. Further, treatment administrations had no effect on IGF-1 mRNA expression at any collection time-point. In summary, MRK-016 can protect against LPS-induced deficits in memory acquisition and consolidation, in this hippocampus-dependent paradigm, though this protection occurs independently of recovery of BDNF expression.