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Trophic factors are secreted proteins that can modulate neuronal integrity, structure, and function. Previous preclinical studies have shown synergistic effects on decreasing apoptosis and improving behavioral performance after stroke when combining two such trophic factors, erythropoietin (EPO) and insulin-like growth factor-1 (IGF-1). However, EPO can elevate the hematocrit level, which can be life-threatening for non-anemic individuals. A chemically engineered derivative of EPO, carbamoylated EPO (CEPO), does not impact hematological parameters but retains neurotrophic effects similar to EPO. To obtain insight into CEPO and IGF-1 combination signaling, we examined immediate early gene (IEG) expression after treatment with CEPO, IGF-1, or CEPO + IGF-1 in rat pheochromocytoma (PC-12) cells and found that combining CEPO and IGF-1 produced a synergistic increase in IEG expression. An in vivo increase in the protein expression of Npas4 and Nptx2 was also observed in the rat hippocampus. We also examined which kinase signaling pathways might be mediating these effects and found that while AKT inhibition did not alter the pattern of IEG expression, both ERK and JAK2 inhibition significantly decreased IEG expression. These results begin to define the molecular effects of combining CEPO and IGF-1 and indicate the potential for these trophic factors to produce positive, synergistic effects. [ABSTRACT FROM AUTHOR]

Physical activity has shown tremendous promise for counteracting cognitive aging, but also tremendous variability in cognitive benefits. We describe evidence for how exercise affects cognitive and brain aging, and whether cardiorespiratory fitness is a key factor. We highlight a brain network framework as a valuable paradigm for the mechanistic insight needed to tailor physical activity for cognitive benefits. [ABSTRACT FROM AUTHOR]

Rationale: MDMA or Ecstasy has made a resurgence in popularity and the majority of users consist of teenagers and adolescents. Therefore, it is important to determine whether MDMA causes long‐term damage and what this damage entails. There is an ongoing debate about possible neurocognitive changes in 3,4‐methylenedioxymethamphetamine (MDMA) users related to MDMA's neurotoxic potential. Multiple neuroimaging studies have shown that Ecstasy use leads to lower serotonin transporter (SERT) availability in multiple brain regions. This may express itself in a loss of cognitive functions like memory, attention and executive function. However, there is increasing evidence reporting that MDMA's induced serotonergic adaptations are reversible over time. The question we thus address is whether the recovery of SERT function predicts a recovery of cognitive function. Objectives: This review aims to investigate MDMA's long‐term effects on SERT availability and cognitive functioning. Methods: A literature search was performed in PubMed. Studies that investigated the effects of MDMA on both SERT availability and cognitive performance were eligible for inclusion. Results: SERT availability positively correlated with time of abstinence, whereas memory performance did not show this correlation, but remained impaired in MDMA users. No significant correlation between SERT availability and memory function was found (r = 0.232, p = 0.581; r = 0.176, p = 0.677). Conclusions: The main findings of this review are that MDMA‐use leads to an acute decrease in SERT availability and causes an impairment in cognitive functions, mostly memory. However, SERT availability recovers with sustained abstinence while memory function does not. This suggests that SERT availability is not a biomarker for MDMA‐induced cognitive impairment and likely also not for MDMA‐induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Associations between cardiorespiratory fitness and brain health in healthy older adults have been reported using a variety of cardiorespiratory fitness estimates (CRFe). Using commonly used methods to determine CRF, we assessed the relationship between CRFe and executive function performance. Healthy older adults (n = 60, mean age 68 years, 77% women), underwent three CRF tests: a Maximal Graded Exercise Test performed on a cycle ergometer, the Rockport Fitness Walking Test, and a Non-Exercise Prediction Equation. Executive function was assessed by a computerized cognitive assessment using an N-Back task (updating cost) and a Stroop task (interference cost, global and local switch cost). Multiple hierarchical regression analyses were conducted to assess the relationship between different CRFe and executive function performance. Regardless of age and education, cardiorespiratory fitness estimated from the Maximal Graded Exercise Test and the Rockport Fitness Walking Test was significantly associated with the global switch cost. All CRFe were associated with the interference cost. No association was observed between CRFe and local switching costs or the updating costs. In the present study, not all subcomponents of executive function were related to CRFe. Interestingly, the executive functions that were associated with CRFe are those that are known to be the most affected by aging. [ABSTRACT FROM AUTHOR]

It is well established that sex differences exist in the manifestation of vascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. Here, we investigated the possible role of sex on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Pseudo-continuous arterial spin labeling (pCASL) data were collected during a hypercapnia challenge. Aortic pulse wave velocity (PWV) data was acquired using cine phase contrast velocity series. Cognitive function was assessed with a comprehensive neuropsychological battery, and a composite score for EF was calculated using four cognitive tests from the neuropsychological battery. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF, but not between CVR and EF. Together, our results indicate that the relationships between central stiffness, cerebral hemodynamics and cognition are in part mediated by sex. [ABSTRACT FROM AUTHOR]

Exposure to stress during adolescence is a risk factor for developing several psychiatric disorders, many of which involve prefrontal cortex (PFC) dysfunction. The human PFC and analogous rodent medial prefrontal cortex (mPFC) continue to mature functionally and anatomically during adolescence, and some of these maturational events coincide with pubertal onset. As developing brain regions are more susceptible to the negative effects of stress, this may make puberty especially vulnerable. To test this, we exposed male and female rats to isolation and restraint stress during the onset of puberty or during the post‐pubertal period of adolescence. In young adulthood, both stressed groups and an unstressed control group underwent testing on a battery of tasks to assess emotional and cognitive behaviors, and the volume of the mPFC was quantified postmortem. Factor analysis revealed only subjects stressed peri‐pubertally showed a long‐term deficiency compared to controls in prepulse inhibition. Additionally, both sexes showed volumetric mPFC decreases following adolescent stress, and these losses were most pronounced in females. Our findings suggest that pubertal onset may be a vulnerable window wherein adolescents are most susceptible to the negative consequences of stress exposure. Furthermore, it highlights the importance of accounting for pubertal status when studying adolescents. [ABSTRACT FROM AUTHOR]

Context: Although diabetic peripheral neuropathy (DPN) is predominantly considered a disorder of the peripheral nerves, some evidence for central nervous system involvement has recently emerged. However, whether or to what extent the microstructure of central somatosensory tracts may be injured remains unknown.Objective: This work aimed to detect the microstructure of central somatosensory tracts in type 2 diabetic patients and to correlate it with the severity of DPN.Methods: A case-control study at a tertiary referral hospital took place with 57 individuals with type 2 diabetes (25 with DPN, 32 without DPN) and 33 nondiabetic controls. The fractional anisotropy (FA) values of 2 major somatosensory tracts (the spinothalamic tract and its thalamocortical [spino-thalamo-cortical, STC] pathway, the medial lemniscus and its thalamocortical [medial lemnisco-thalamo-cortical, MLTC] pathway) were assessed based on diffusion tensor tractography. Regression models were further applied to detect the association of FA values with the severity of DPN in diabetic patients.Results: The mean FA values of left STC and left MLTC pathways were significantly lower in patients with DPN than those without DPN and controls. Moreover, FA values of left STC and left MLTC pathways were significantly associated with the severity of DPN (expressed as Toronto Clinical Scoring System values) in patients after adjusting for multiple confounders.Conclusion: Our findings demonstrated the axonal degeneration of central somatosensory tracts in type 2 diabetic patients with DPN. The parallel disease progression of the intracranial and extracranial somatosensory system merits further attention to the central nerves in diabetic patients with DPN. [ABSTRACT FROM AUTHOR]

Sports-related concussion (SRC) is a complex and heterogeneous injury with psychological, cognitive and functional consequences. Advances in diffusion magnetic resonance imaging (dMRI) allow sensitive measurement of white matter pathology post-SRC and may provide insight into injury and recovery. We systematically reviewed and meta-analyzed the literature examining dMRI alongside cognitive, emotional or motor assessments to determine relationships between these analyses. Sixteen studies examining young athletes (n = 6) or retired professionals (n = 10) met the inclusion criteria, with 12 emotional, 10 cognitive and four motor assessments. Studies had heterogeneous methodology, moderate quality and modest sample sizes. Fractional anisotropy (FA) was the most frequent dMRI metric, with SRC-induced changes described most commonly in the frontal lobe and least in the cerebellum and brainstem. There is an emerging complementary role for dMRI as part of a comprehensive assessment battery for SRC. However, larger-scale studies with broader subject populations (specifically, in females and in the 30–45 year age range) are needed to corroborate findings and determine the true diagnostic utility of dMRI post-SRC. [ABSTRACT FROM AUTHOR]

Objective: To investigate regional white matter fibers loss in Leukoaraiosis (LA) and its relationship with cognitive impairments. Methods: Fifty‐six participants with LA and 38 healthy controls underwent clinical evaluations and MR scans. Participants with LA were classified as cognitively normal (LA‐NC, n = 18), vascular cognitive impairment of none dementia (LA‐VCIND, n = 24), and vascular dementia (LA‐VaD, n = 14) by Mini‐Mental State Examination and Clinical Dementia Rating. Cognitive domains including visual‐spatial, naming, attention, language, abstraction, memory, and orientation were assessed. With the use of Tract‐based spatial statistics, mean fractional anisotropy (FA) of major white matter fiber tracts were compared between LA and controls and among LA groups with varying levels of cognitive impairments. Regression analyses were performed to evaluate relationships between FA values and cognitive performance. Results: Participants showed significant FA reduction in the corpus callosum (CC), bilateral corona radiata, anterior limb of the internal capsule, external capsule, posterior thalamic radiation, and superior longitudinal fasciculus compared to controls and across LA groups. The LA‐VaD group showed consistent damage in the body and genu of CC compared to the LA‐NC and LA‐VCIND groups. A positive correlation between visual‐spatial and FA reduction in right anterior corona radiates in LA‐VCIND and body of CC in LA‐ VaD. Interpretation: We found regional fiber loss in the CC across the cognitive spectrum in patients with LA and correlations between FA and visuospatial impairment in the anterior corona radiata in patients with LA‐VCIND and in the body of CC in patients with LA‐VaD. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer's disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal injury is implicated in disrupting microtubule function, providing the potential context for pathologies of tau and amyloid to develop. The neuropathology of post-traumatic dementias is increasingly well characterised, with recent work focusing on chronic traumatic encephalopathy (CTE). However, clinical diagnosis of post-traumatic dementia is problematic. It is often difficult to disentangle the direct effects of TBI from those produced by progressive neurodegeneration or other post-traumatic sequelae such as psychiatric impairment. CTE can only be confidently identified at postmortem and patients are often confused and anxious about the most likely cause of their post-traumatic problems. A new approach to the assessment of the long-term effects of TBI is needed. Accurate methods are available for the investigation of other neurodegenerative conditions. These should be systematically employed in TBI. MRI and positron emission tomography neuroimaging provide biomarkers of neurodegeneration which may be of particular use in the postinjury setting. Brain atrophy is a key measure of disease progression and can be used to accurately quantify neuronal loss. Fluid biomarkers such as neurofilament light can complement neuroimaging, representing sensitive potential methods to track neurodegenerative processes that develop after TBI. These biomarkers could characterise endophenotypes associated with distinct types of post-traumatic neurodegeneration. In addition, they might profitably be used in clinical trials of neuroprotective and disease-modifying treatments, improving trial design by providing precise and sensitive measures of neuronal loss. [ABSTRACT FROM AUTHOR]

Prognostic modeling in moderate to severe traumatic brain injury (TBI) has historically focused primarily on the projection of crude outcomes such as the risk of mortality and disability. Initial work in this area has perpetuated the notion that prognosis after moderate to severe TBI can be measured as a single, static, and dichotomous outcome. However, more recent conceptualizations describe moderate to severe TBI as the initiation of a chronic disease state with high levels of inter-individual variability in terms of symptom manifestation and disease progression. Unfortunately, existing prognostic models provide limited insight into the extent of chronic cognitive and neurodegenerative changes experienced by moderate to severe TBI survivors. Though prior research has identified a variety of acute factors that appear to influence post-injury cognitive and neuropathological outcomes, an empirically supported framework for prognostic modeling of these injury-distal outcomes does not exist. The current review considers the literature on an expanded array of empirically supported predictors (both premorbid and injury-related) in association with long-term sequelae of moderate to severe TBI. We also provide a theoretical framework and statistical approach for prognostic modeling in moderate to severe TBI in order to unify efforts across research groups and facilitate important progress in this research area. [ABSTRACT FROM AUTHOR]

Background: Exercise helps many aspects of cognition, but at this time no review has summarized the literature on the association of exercise and physical fitness with attention. Method: A systematic search was conducted on PubMed, ISI Web of Knowledge, and Scopus databases. After inclusion criteria assessment, a final pool of 44 articles was included. A number of behavioral and neurophysiological indices of attention were examined. Results: The majority of studies showed an increase in performance of attention. Acute exercise results in greater enhancement of attention in those who are active. There was an association of aerobic fitness and attention in the young and old, but not in young adults. Aerobic exercise training interventions generally resulted in positive changes, while some resistance training studies detected no evidence of an effect. Not all forms of exercise were effective. Shorter interventions were inferior with respect to longer ones. Most studies were rated with a moderate methodological quality. Conclusion: There is an association of aerobic exercise (acute and chronic) and aerobic fitness with attention. Future research should determine the dose and mechanisms by which different forms of physical activity and exercise may influence the development of different components of attention along the lifespan. [ABSTRACT FROM AUTHOR]

Traumatic brain injuries (TBI) have received widespread media attention in recent years as being a risk factor for the development of dementia and chronic traumatic encephalopathy (CTE). This has sparked fears about the potential long-term effects of TBI of any severity on cognitive aging, leading to a public health concern. This article reviews the evidence surrounding TBI as a risk factor for the later development of changes in brain structure and function, and an increased risk of neurodegenerative disorders. A number of studies have shown evidence of long-term brain changes and accumulation of pathological biomarkers (e.g., amyloid and tau proteins) related to a history of moderate-to-severe TBI, and research has also demonstrated that individuals with moderate-to-severe injuries have an increased risk of dementia. While milder injuries have been found to be associated with an increased risk for dementia in some recent studies, reports on long-term brain changes have been mixed and often are complicated by factors related to injury exposure (i.e., number of injuries) and severity/complications, psychiatric conditions, and opioid use disorder. CTE, although often described as a neurodegenerative disorder, remains a neuropathological condition that is poorly understood. Future research is needed to clarify the significance of CTE pathology and determine whether that can explain any clinical symptoms. Overall, it is clear that most individuals who sustain a TBI (particularly milder injuries) do not experience worse outcomes with aging, as the incidence for dementia is found to be less than 7% across the literature. [ABSTRACT FROM AUTHOR]

Copyright of Revista Neuropsicologia Latinoamericana is the property of Yves Joannette and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Movement & Sport Sciences / Science & Motricité is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Previous studies have found positive associations between cardiorespiratory fitness (CRF) and cognitive performance in older people but data are inconsistent and have methodological limitations.Objective: Our aim was to study the longitudinal associations of CRF with executive functions, processing speed and memory as well as with the overall cognitive function in older people at risk for cognitive impairment.Methods: Participants (n = 421), mean age 69.0, were a sub-sample of The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). To be eligible, individuals were required to be 60-77 years old with a CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. CRF was assessed as peak oxygen uptake (VO2peak, L/min) measured directly in a symptom-limited maximal exercise test on cycle ergometer at baseline and at 24 months. Cognitive performance was assessed using an extensive neuropsychological test battery (NTB) at baseline and at 24 months. NTB data were standardized to Z scores, and analyzed with the linear mixed model.Results: Over two years, VO2peak was associated with NTB total score (β= 0.12, p = 0.01), executive functions (β= 0.16, p = 0.01), and processing speed (β= 0.25, p < 0.001), but not with memory (β= 0.11, p = 0.12).Conclusion: Over two years follow-up, CRF was associated with executive functions and processing speed, and was related also to the overall cognitive function. [ABSTRACT FROM AUTHOR]

Background and objective: Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI. Methods: Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. MHL was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months. Results: There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions. Conclusions: Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity. [ABSTRACT FROM AUTHOR]

Background and objective: Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI. Methods: Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months postinjury. MHL was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months. Results: There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions. Conclusions: Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a leading cause of disability and produces a wide range of cognitive, emotional, and physical consequences. The impact of TBI on cognition is among the most important questions in this field but remains incompletely understood. The immediate cognitive effects of concussion, while usually short-lived, may be profound and lasting in some individuals, and long-term sequelae of TBI may include dementia of several varieties including post-traumatic leukoencephalopathy, chronic traumatic encephalopathy, and Alzheimer's disease. Whereas the etiopathogenesis of cognitive dysfunction after TBI remains uncertain, a reasonable point to begin is a focus on the white matter of the brain, where the neuropathological lesion known as diffuse axonal injury (DAI) is routinely identified. White matter is not typically accorded the significance granted to cortical gray matter in discussions of cognitive dysfunction and dementia, but increasing evidence is accumulating to suggest that cognitive decline after TBI is a direct result of white matter injury, and that lesions in this brain component are crucial in the sequence of events leading ultimately to dementia of several types. In this review, we consider the topic of white matter and cognition in TBI, beginning with DAI and proceeding to the role of inflammation in the pathogenesis of cognitive dysfunction and dementia that can follow. A brief review of possible therapeutic options will also be offered, including the use of anti-inflammatory agents and the exploitation of white matter plasticity, to treat acute and post-acute injuries, and lower the incidence of dementia resulting from TBI. [ABSTRACT FROM AUTHOR]

Background: There is very little evidence available on the effects of yoga-based breathing practices on response inhibition. The current study used stop-signal paradigm to assess the effects of yoga breathing with intermittent breath holding (YBH) on response inhibition among healthy volunteers. Materials and Methods: Thirty-six healthy volunteers (17 males + 19 females), with mean age of 20.31 ± 3.48 years from a university, were recruited in a within-subject repeated measures (RM) design. The recordings for stop signal task were performed on three different days for baseline, post-YBH, and post yogic breath awareness (YBA) sessions. Stop-signal reaction time (SSRT), mean reaction time to go stimuli (go RT), and the probability of responding on-stop signal trials (p [r/s]) were analyzed for 36 volunteers using RM analysis of variance. Results: SSRT reduced significantly in both YBH (218.33 ± 38.38) and YBA (213.15 ± 37.29) groups when compared to baseline (231.98 ± 29.54). No significant changes were observed in go RT and p (r/s). Further, the changes in SSRT were not significantly different among YBH and YBA groups. Conclusion: Both YBH and YBA groups were found to enhance response inhibition in the stop-signal paradigm. YBH could be further evaluated in clinical settings for conditions where response inhibition is altered. [ABSTRACT FROM AUTHOR]

Background: Greater physical fitness is associated with reduced rates of cognitive decline in older people; however, the mechanisms by which this occurs are still unclear. One potential mechanism is aortic stiffness, with increased stiffness resulting in higher pulsatile pressures reaching the brain and possibly causing progressive micro-damage. There is limited evidence that those who regularly exercise may have lower aortic stiffness.Objective: To investigate whether greater fitness and lower aortic stiffness predict better cognitive performance in older people and, if so, whether aortic stiffness mediates the relationship between fitness and cognition.Methods: Residents of independent living facilities, aged 60-90, participated in the study (N = 102). Primary measures included a computerized cognitive assessment battery, pulse wave velocity analysis to measure aortic stiffness, and the Six-Minute Walk test to assess fitness. Based on hierarchical regression analyses, structural equation modelling was used to test the mediation hypothesis.Results: Both fitness and aortic stiffness independently predicted Spatial Working Memory (SWM) performance, however no mediating relationship was found. Additionally, the derived structural equation model shows that, in conjunction with BMI and sex, fitness and aortic stiffness explain 33% of the overall variation in SWM, with age no longer directly predicting any variation.Conclusions: Greater fitness and lower aortic stiffness both independently predict better SWM in older people. The strong effect of age on cognitive performance is totally mediated by fitness and aortic stiffness. This suggests that addressing both physical fitness and aortic stiffness may be important to reduce the rate of age associated cognitive decline. [ABSTRACT FROM AUTHOR]

Background: We aimed to explore the relation between the microstructural integrity of white matter using the technique of diffusion tensor imaging (DTI) and changes of cognition in leukoaraiosis (LA). Methods: Fifty patients with LA and 50 age- and gender-matched controls were recruited consecutively. The average values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal-appearing white matter (NAWM) from the regions of interest (ROIs). Results: We found significantly decreased FA and increased MD in WMLs at the 5 ROIs than that in NAWM and controls (p < 0.05). The values of FA in NAWM were significantly lower at centrum semiovale and posterior periventricular white matter than those of controls (p < 0.05). The values of MD in NAWM were significantly higher at the anterior periventricular white matter and corpus callosum than those of controls (p < 0.05). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.420, p = 0.028). Conclusions: DTI may provide some important information about the cognitive dysfunction in patients with LA, which may largely attribute to the "disconnection" of cortico-subcortical pathways, with the evidence of reduced FA and increased MD. [ABSTRACT FROM AUTHOR]

Cerebellar volume declines with aging. Few studies have investigated age differences in regional cerebellar volume (RCV) and their association with motor and cognitive function. In 213 healthy older adults, we investigated the association of age with motor skills, cognition and RCV. Subsequently, we studied the association of RCV with motor skills and cognition. RCVs were derived from T1-weighted MRI scans using the automated SUIT segmentation method and clustered using principal component analysis (PCA). Motor skill (manual dexterity, tapping speed, bimanual visuomotor coordination, grip force) and cognition (mental rotation, verbal memory, inhibition, mental flexibility) were assessed. Behavioral measures were clustered into compounds using PCA: left hand motor skill, right hand motor skill, verbal memory and mental flexibility, and mental rotation & inhibition. Volume of the rostral middle frontal gyri (rMFG) and premotor areas (PMA) were related to performance for reference. Analyses were adjusted for age, sex, and education. Volume of the cerebellar anterior lobe and top of the superior posterior lobe were positively associated with motor skill. Volume of the bottom part of the posterior superior lobe and the inferior posterior lobe was positively associated with cognition. PMA volume was associated with cognition and motor skill and rMFG volume with motor skill. Although these results did not survive FDR correction, their effect sizes suggest that regional cerebellar volume selectively contributes to cognitive and motor skill. Effect sizes of cerebellar associations with performance were similar to those of rMFG/PMA and performance suggesting parallel contributions to performance. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the association of chronotropic response (CR) and heart rate (HR) recovery- two indices of cardiovascular function within the context of a graded exercise test- with cognitive performance in a cognitively healthy, late-middle-aged cohort at risk for Alzheimer's disease (AD). Ninety participants (age = 63.52±5.86 years; 65.6% female) from the Wisconsin Registry for Alzheimer's Prevention participated in this study. They underwent graded exercise testing and a comprehensive neuropsychological assessment that assessed the following four cognitive domains: Immediate Memory, Verbal & Learning Memory, Working Memory, and Speed & Flexibility. Regression analyses, adjusted for age, sex, and education, were used to examine the association between CR, HR recovery, and cognition. We found significant associations between CR and cognitive performance in the domains of Immediate Memory, Verbal Learning & Memory, and Speed & Flexibility. In contrast, HR recovery was not significantly associated with cognitive function. The association between CR and cognition persisted even after controlling for HR recovery. Together, these findings indicatethat, in a cognitively normal, late-middle-aged cohort, CR is a stronger correlate of cognitive performance than HR recovery. Overall, this study reinforces the idea that cardiovascular health plays an important role in cognitive function, specifically in a cohort at risk for AD; and that interventions that promote vascular health may be a viable pathway to preventing or slowing cognitive decline due to AD. [ABSTRACT FROM AUTHOR]

Importance: Despite its high heritability, few risk genes have been identified for attention-deficit/hyperactivity disorder (ADHD). Brain-based phenotypes could aid gene discovery. There is a myriad of structural and functional connections that support cognition. Disruption of such connectivity is a key pathophysiologic mechanism for ADHD, and identifying heritable phenotypes within these connections could provide candidates for genomic studies.Objective: To identify the structural and functional connections that are heritable and pertinent to ADHD.Design, Setting, and Participants: Members of extended multigenerational families enriched for ADHD were evaluated. Structural connectivity was defined by diffusion tensor imaging (DTI) of white matter tract microstructure and functional connectivity through resting-state functional magnetic resonance imaging (rsfMRI). Heritability and association with ADHD symptoms were estimated in 24 extended multigenerational families enriched for ADHD (305 members with clinical phenotyping, 213 with DTI, and 193 with rsfMRI data). Findings were confirmed in 52 nuclear families (132 members with clinical phenotypes, 119 with DTI, and 84 with rsfMRI). The study and data analysis were conducted from April 1, 2010, to September 1, 2016.Results: In the 52 nuclear families, 86 individuals (65.2%) were male and the mean (SD) age at imaging was 20.9 (15.0) years; in the 24 multigenerational extended families, 145 individuals (47.5%) were male and mean age at imaging was 30.4 (19.7) years. Microstructural properties of white matter tracts connecting ipsilateral cortical regions and the corpus callosum were significantly heritable, ranging from total additive genetic heritability (h2) = 0.69 (SE, 0.13; P = .0000002) for radial diffusivity of the right superior longitudinal fasciculus to h2 = 0.46 (SE, 0.15; P = .0009) for fractional anisotropy of the right inferior fronto-occipital fasciculus. Association with ADHD symptoms was found in several tracts, most strongly for the right superior longitudinal fasciculus (t = -3.05; P = .003). Heritable patterns of functional connectivity were detected within the default mode (h2 = 0.36; SE, 0.16; cluster level significance, P < .002), cognitive control (h2 = 0.32; SE, 0.15; P < .002), and ventral attention networks (h2 = 0.36; SE, 0.16; P < .002). In all cases, subregions within each network showed heritable functional connectivity with the rest of that network. More symptoms of hyperactivity/impulsivity (t = -2.63; P = .008) and inattention (t = -2.34; P = .02) were associated with decreased functional connectivity within the default mode network. Some cross-modal correlations were purely phenotypic, such as that between axial diffusivity of the right superior longitudinal fasciculus and heritable aspects of the default mode network (phenotypic correlation, ρp = -0.12; P = .03). A genetic cross-modal correlation was seen between the ventral attention network and radial diffusivity of the right inferior fronto-occipital fasciculus (genetic correlation, ρg = -0.45, P = .02).Conclusions: Analysis of data on multigenerational extended and nuclear families identified the features of structural and functional connectivity that are both significantly heritable and associated with ADHD. In addition, shared genetic factors account for some phenotypic correlations between functional and structural connections. Such work helps to prioritize the facets of the brain's connectivity for future genomic studies. [ABSTRACT FROM AUTHOR]

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts. [ABSTRACT FROM AUTHOR]

BackgroundCognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the effects of EPO on neural circuitry activity during working memory (WM) performance.MethodPatients with treatment-resistant major depression, who were moderately depressed, or with BD in partial remission, were randomized to eight weekly infusions of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task.ResultsEPO improved WM accuracy compared with saline (p = 0.045). Whole-brain analyses revealed that EPO increased WM load-related activity in the right superior frontal gyrus (SFG) compared with saline (p = 0.01). There was also enhanced WM load-related deactivation of the left hippocampus in EPO-treated compared to saline-treated patients (p = 0.03). Across the entire sample, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28–0.30, p < 0.05). The effects of EPO were not associated with changes in mood or red blood cells (p ⩾0.08).ConclusionsThe present findings associate changes in WM-load related activity in the right SFG and left hippocampus with improved executive function in EPO-treated patients. Clinical trial registration: clinicaltrials.gov: NCT00916552. [ABSTRACT FROM AUTHOR]

Background: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. Methods: Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [123I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n = 13) or zuclopenthixol (n = 9), 22 patients were reexamined. Results: Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P = .003) and planning time (r = -0.436, P = .048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P = .003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P = .016). Conclusions: Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms. [ABSTRACT FROM AUTHOR]

The rising prevalence of type 2 diabetes (T2DM) and hypertension in older adults, and the deleterious effect of these conditions on cerebrovascular and brain health, is creating a growing discrepancy between the "typical" cognitive aging trajectory and a "healthy" cognitive aging trajectory. These changing health demographics make T2DM and hypertension important topics of study in their own right, and warrant attention from the perspective of cognitive aging neuroimaging research. Specifically, interpretation of individual or group differences in blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) or positron emission tomography (PET H2O15) signals as reflective of differences in neural activation underlying a cognitive operation of interest requires assumptions of intact vascular health amongst the study participants. Without adequate screening, inclusion of individuals with T2DM or hypertension in "healthy" samples may introduce unwanted variability and bias to brain and/or cognitive measures, and increase potential for error.We conducted a systematic review of the cognitive aging neuroimaging literature to document the extent to which researchers account for these conditions. Of the 232 studies selected for review, few explicitly excluded individuals with T2DM (9%) or hypertension (13%). A large portion had exclusion criteria that made it difficult to determine whether T2DM or hypertension were excluded (44 and 37%), and many did not mention any selection criteria related to T2DM or hypertension (34 and 22%). Of all the surveyed studies, only 29% acknowledged or addressed the potential influence of intersubject vascular variability on the measured BOLD or PET signals. To reinforce the notion that individuals with T2DM and hypertension should not be overlooked as a potential source of bias, we also provide an overview of metabolic and vascular changes associated with T2DM and hypertension, as they relate to cerebrovascular and brain health. [ABSTRACT FROM AUTHOR]

To investigate which neural correlates are associated with successful working memory performance, fMRI was recorded in healthy younger and older adults during performance on an n-back task with varying task demands. To identify functional networks supporting working memory processes, we used independent component analysis (ICA) decomposition of the fMRI data. Compared to younger adults, older adults showed a larger neural (BOLD) response in the more complex (2-back) than in the baseline (0-back) task condition, in the ventral lateral prefrontal cortex (VLPFC) and in the right fronto-parietal network (FPN). Our results indicated that a higher BOLD response in the VLPFC was associated with increased performance accuracy in older adults, in both the baseline and the more complex task condition. This ‘BOLD-performance’ relationship suggests that the neural correlates linked with successful performance in the older adults are not uniquely related to specific working memory processes present in the complex but not in the baseline task condition. Furthermore, the selective presence of this relationship in older but not in younger adults suggests that increased neural activity in the VLPFC serves a compensatory role in the aging brain which benefits task performance in the elderly. [ABSTRACT FROM AUTHOR]

Aerobic fitness is associated with white matter integrity (WMI) in adults as measured by diffusion tensor imaging (DTI). This study examined the effect of an 8-month exercise intervention on WMI in children. Participants were 18 sedentary, overweight (BMI ≥85th percentile) 8- to 11-year-old children (94% Black), randomly assigned to either an aerobic exercise (n = 10) or sedentary attention control group (n = 8). Each group was offered an instructor-led after-school program every school day for approximately 8 months. Before and after the program, all subjects participated in DTI scans. Tractography was conducted to isolate the superior longitudinal fasciculus and investigate whether the exercise intervention affected WMI in this region. There was no group by time interaction for WMI in the superior longitudinal fasciculus. There was a group by time by attendance interaction, however, such that higher attendance at the exercise intervention, but not the control intervention, was associated with increased WMI. Heart rate and the total dose of exercise correlated with WMI changes in the exercise group. In the overall sample, increased WMI was associated with improved scores on a measure of attention and improved teacher ratings of executive function. This study indicates that participating in an exercise intervention improves WMI in children as compared to a sedentary after-school program. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives Executive function impairments are a core feature of bipolar I disorder ( BD-I), not only present during acute episodes but also persisting following remission of mood symptoms. Despite advances in knowledge regarding the neural basis of executive functions in healthy subjects, research into morphological abnormalities underlying the deficits in BD-I is lacking. Methods Patients with BD-I within three months of sustained remission from their first manic episode (n = 41) underwent neuropsychological testing and a 3T magnetic resonance imaging scan and were compared to healthy subjects matched for age, sex, and premorbid IQ (n = 30). Group dorsolateral prefrontal cortex ( DLPFC; Brodmann areas 9 and 46) and caudate volumes were examined and analyzed for relationships with the average score from three computerized tests of executive function: Spatial Working Memory, Stockings of Cambridge, and Intradimensional/Extradimensional Shift. Results Right caudate volumes were enlarged in patients ( z = 3.57, p < 0.05 corrected). No differences in DLPFC volumes were found. Patients showed large deficits in executive function relative to healthy subjects ( d = −0.92, p < 0.001). While in healthy subjects, a larger right ( r = +0.39, p < 0.05) and left ( r = +0.44, p < 0.05) caudate was associated with better executive function score, in patients, larger right ( r = −0.36, p < 0.05) and left ( r = −0.34, p < 0.05) volumes correlated with poorer performance. Conclusions Although the etiology of gray matter changes is unknown, volume increases in the right caudate may be an important factor underlying executive function impairments during remission in patients with BD-I. [ABSTRACT FROM AUTHOR]

Background. Attention deficit hyperactivity disorder (ADHD) is recognized as an early-onset neuropsychiatric disorder with executive dysfunctions and neurobiological deficits. The authors compared executive functions and microstructural integrity of the frontostriatal circuit in children with ADHD and typically developing children. Method. We assessed 25 children with ADHD and 25 age-, sex-, handedness- and intelligence-matched typically developing children by using psychiatric interviews, the Wechsler Intelligence Scale for Children - third edition, and the tasks involving executive functions in the Cambridge Neuropsychological Test Automated Battery. The frontostriatal tracts were reconstructed by diffusion spectrum imaging tractography and were subdivided into four functionally distinct segments, including dorsolateral, medial prefrontal, orbitofrontal and ventrolateral tracts. Tract- specific and matched case-control analyses were used and generalized fractional anisotropy values were computed. Results. Children with ADHD had lower generalized fractional anisotropy of all the bilateral frontostriatal fiber tracts and poorer performance in verbal and spatial working memory, set-shifting, sustained attention, cognitive inhibition and visuospatial planning. The symptom severity of ADHD and the executive functioning performance significantly correlated with integrity of the frontostriatal tracts, particularly the left orbitofrontal and ventrolateral tracts. Children with ADHD also demonstrated loss of the leftward asymmetry in the dorsolateral and medial prefrontal tracts that was present in typically developing children. Conclusions. Our findings demonstrate disturbed structural connectivity of the frontostriatal circuitry in children with ADHD and add new evidence of associations between integrity of the frontostriatal tracts and measures of core symptoms of ADHD and a wide range of executive dysfunctions in both groups. [ABSTRACT FROM AUTHOR]

Vascular factors play a role in the etiology of Alzheimer's disease (AD), presumably due to emergence of white matter lesions. However, important white matter structures involved in the etiology of AD, including the corpus callosum (CC), remain invariably free from macroscopical white matter lesions, although loss of microstructural integrity assessed with diffusion tensor imaging (DTI) has been described in the CC. Vascular factors have been related to these microstructural white matter changes too, but little is known about their effect on the CC. In 499 subjects with cerebral small vessel disease, aged 50-85 years, we cross-sectionally investigated the relation between hypertension, hypertension treatment status, the microstructural integrity of the CC using DTI, and the attendant cognitive performance. Fractional anisotropy and mean diffusivity were calculated in four substructures of the CC (genu, anterior body, posterior body, and splenium). Differences between groups were calculated with analysis of variance, adjusted for age, gender, and cardiovascular risk factors. Compared with normotensive subjects, hypertensive subjects had a lower fractional anisotropy in the splenium and a significant higher mean diffusivity in both the anterior body and the splenium; this was most noticeable in treated uncontrolled hypertensive subjects. Furthermore we found that microstructural integrity of the CC was related to global cognition. Of this relation, 14 to 60% was explained by the mediating effect of small vessel disease elsewhere in the white matter. Our findings indicate that adequate blood pressure treatment might postpone these changes and the attendant cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion: Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions: We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted. [ABSTRACT FROM AUTHOR]

Objective: To study the relationship between thalamic glucose metabolism and neurological outcome after severe traumatic brain injury (TBI). Methods: Forty-nine patients with severe and closed TBI and 10 healthy control subjects with 18F-FDG PET were studied. Patients were divided into three groups: MCS&VS group ( n = 17), patients in a vegetative or a minimally conscious state; In-PTA group ( n = 12), patients in a state of post-traumatic amnesia (PTA); and Out-PTA group ( n = 20), patients who had emerged from PTA. SPM5 software implemented in MATLAB 7 was used to determine the quantitative differences between patients and controls. FDG-PET images were spatially normalized and an automated thalamic ROI mask was generated. Group differences were analysed with two sample voxel-wise t-tests. Results: Thalamic hypometabolism was the most prominent in patients with low consciousness (MCS&VS group) and the thalamic hypometabolism in the In-PTA group was more prominent than that in the Out-PTA group. Healthy control subjects showed the greatest thalamic metabolism. These differences in metabolism were more pronounced in the internal regions of the thalamus. Conclusions: The results confirm the vulnerability of the thalamus to suffer the effect of the dynamic forces generated during a TBI. Patients with thalamic hypometabolism could represent a sub-set of subjects that are highly vulnerable to neurological disability after TBI. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular reactivity (CVR) refers to the responsiveness of cerebral vasculature to vasoactive stimuli. CVR is an indicator of brain health and can be assessed using vasodilatory techniques and magnetic resonance imaging (MRI). Using such approaches, some researchers have explored the relationship between CVR and cognition; here we systematically review this work.Results: We extracted information pertaining to: (1) study location and design, participant characteristics, sample sizes, (2) design of vascular challenge, end-tidal CO 2 (etCO 2 ) concentrations (if applicable), (3) MRI protocol, (4) cognitive assessment, (5) CVR values, and outcomes of statistical analyses with cognitive tests. Five studies assessed participants with cognitive impairment compared to controls, one studied patients with multiple sclerosis with or without cognitive impairment compared to controls, one examined patients with moyamoya disease with or without cognitive impairment, two investigated patients with Type 2 diabetes mellitus (T2DM), and one was a cross-sectional study with younger and older healthy adults. Cognition was typically probed using the MMSE and tests of executive function, while a number of vasodilatory techniques were employed.Conclusion: CVR was associated with cognition in six of ten studies, but heterogeneity of study samples, designs and vasodilatory methods may have a role in the inconsistent findings. We make recommendations for future research that includes use of a multi-domain cognitive assessment and standardised hypercapnic challenge with MRI. [ABSTRACT FROM AUTHOR]