Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ɛ4 carriers

BackgroundThe possibility that ɛ4 may modulate the effects of fitness in the brain remains controversial. The present exploratory FDG-PET study aimed to better understand the relationship among ɛ4, fitness, and cerebral metabolism in 18 healthy aged women (nine carriers, nine noncarriers) during working memory.MethodsParticipants were evaluated using maximal level of oxygen consumption, California Verbal Learning Test, and FDG-PET, which were collected at rest and during completion of the Sternberg working memory task.ResultsResting FDG-PET did not differ between carriers and noncarriers. Significant effects of fitness on FDG-PET during working memory were noted in the ɛ4 carriers only. High fit ɛ4 carriers had greater glucose uptake in the temporal lobe than the low fit ɛ4 carriers, but low fit ɛ4 carriers had greater glucose uptake in the frontal and parietal lobes.ConclusionsWe demonstrate that fitness differentially affects cerebral metabolism in ɛ4 carriers only, consistent with previous findings that the effects of fitness may be more pronounced in populations genetically at risk for cognitive decline.     

IL-4Rα deletion disrupts psychomotor performance and reference memory in mice while sparing behavioural phenotype associated with spatial learning

Contribution of immune mediators, interleukin-4 and interferon gamma to cognitive functioning is receiving increasing attention. However, the fundamental question about how heterodimeric interleukin-4 receptor alpha– and interferon gamma– producing myeloid cells converge to influence hippocampal–dependent spatial memory tasks through immunomodulation of multisensory inputs from other brain areas remains unexplored. Here, we show that mice lacking interleukin-4 receptor alpha are able to successfully learn spatial tasks, while reference memory is impaired. Moreover, the absence of interleukin-4 receptor alpha leads to simultaneous increase in proportions of CD11b + myeloid cells in the hippocampus and thalamus, but not the brainstem during acquisition. Interleukin-4 receptor alpha deletion significantly decreased expression of myeloid cell–derived interferon gamma in the thalamus during the acquisition phase and simultaneously increased brain-derived neurotrophic factor production in the thalamus and brainstem of trained mice. We provide evidence that interleukin-4 receptor alpha is essential for cognitive performance while training–induced alterations in interferon gamma activity and brain-derived neurotrophic factor signalling may contribute to neuromodulation of learned tasks and consequently affect systems–level memory encoding and consolidation.     

Visuo–spatial working memory is an important source of domain-general vulnerability in the development of arithmetic cognition

The study of developmental disorders can provide a unique window into the role of domain-general cognitive abilities and neural systems in typical and atypical development. Mathematical disabilities (MD) are characterized by marked difficulty in mathematical cognition in the presence of preserved intelligence and verbal ability. Although studies of MD have most often focused on the role of core deficits in numerical processing, domain-general cognitive abilities, in particular working memory (WM), have also been implicated. Here we identify specific WM components that are impaired in children with MD and then examine their role in arithmetic problem solving. Compared to typically developing (TD) children, the MD group demonstrated lower arithmetic performance and lower visuo-spatial working memory (VSWM) scores with preserved abilities on the phonological and central executive components of WM. Whole brain analysis revealed that, during arithmetic problem solving, left posterior parietal cortex, bilateral dorsolateral and ventrolateral prefrontal cortex, cingulate gyrus and precuneus, and fusiform gyrus responses were positively correlated with VSWM ability in TD children, but not in the MD group. Additional analyses using a priori posterior parietal cortex regions previously implicated in WM tasks, demonstrated a convergent pattern of results during arithmetic problem solving. These results suggest that MD is characterized by a common locus of arithmetic and VSWM deficits at both the cognitive and functional neuroanatomical levels. Unlike TD children, children with MD do not use VSWM resources appropriately during arithmetic problem solving. This work advances our understanding of VSWM as an important domain-general cognitive process in both typical and atypical mathematical skill development.     

Altered visual–spatial attention to task-irrelevant information is associated with falls risk in older adults

Executive cognitive functions play a critical role in falls risk—a pressing health care issue in seniors. In particular, intact attentional processing is integral for safe mobility and navigation. However, the specific contribution of impaired visual–spatial attention in falls remains unclear. In this study, we examined the association between visual–spatial attention to task-irrelevant stimuli and falls risk in community-dwelling older adults. Participants completed a visual target discrimination task at fixation while task-irrelevant probes were presented in both visual fields. We assessed attention to left and right peripheral probes using event-related potentials (ERPs). Falls risk was determined using the valid and reliable Physiological Profile Assessment (PPA). We found a significantly positive association between reduced attentional facilitation, as measured by the N1 ERP component, and falls risk. This relationship was specific to probes presented in the left visual field and measured at ipsilateral electrode sites. Our results suggest that fallers exhibit reduced attention to the left side of visual space and provide evidence that impaired right hemispheric function and/or structure may contribute to falls.     

Action fluency identifies different sex,age, global cognition,executive function and brain activation profile in non-demented patients with Parkinson’s disease

Journal of Neurology - Patients with Parkinson’s disease (PD) have difficulties processing action words, which could be related to early cognitive decline. The action fluency test can be used...     

Changes of learning and memory ability associated with neuronal nitric oxide synthase in brain tissues of rats with acute alcoholism

INTRODUCTION The discovery of nitric oxide was the greatest achievement of neuro- biology in late 20th century. The discoverers were awarded the Nobel Prize in Physiology and Medicine. Publications on all aspects of nitric oxide run into thousands. Nevert…     

Sporadic Creutzfeldt–Jakob disease is associated with reorganization of metabolic connectivity in a pathological brain network

Background and purpose

Although sporadic Creutzfeldt–Jakob disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, the metabolic brain network associated with sCJD was investigated and its internal network organization was explored.

Methods

We explored 2-[¹⁸F]fluoro-2-deoxy-d -glucose positron emission tomography (FDG-PET) brain scans of 29 sCJD patients, 56 normal controls (NCs) and 46 other dementia patients from two independent centers. sCJD-related pattern (CJDRP) was identified in a cohort of 16 pathologically proven sCJD patients and 16 age-matched NCs using scaled subprofile modeling/principal component analysis and was prospectively validated in an independent cohort of 13 sCJD patients and 20 NCs. The pattern's specificity was tested on other dementia patients and its clinical relevance by clinical correlations. The pattern's internal organization was further studied using graph theory methods.

Results

The CJDRP was characterized by relative hypometabolism in the bilateral caudate, thalami, middle and superior frontal gyri, parietal lobe and posterior cingulum in association with relative hypermetabolism in the hippocampi, parahippocampal gyri and cerebellum. The pattern's expression significantly discriminated sCJD from NCs and other dementia patients (p < 0.005; receiver operating characteristic analysis CJD vs. NCs area under the curve [AUC] 0.90–0.96, sCJD vs. Alzheimer's disease AUC 0.78, sCJD vs. behavioral variant of frontotemporal dementia AUC 0.84). The pattern's expression significantly correlated with cognitive, functional decline and disease duration. The metabolic connectivity analysis revealed inefficient information transfer with specific network reorganization.

Conclusions

The CJDRP is a robust metabolic biomarker of sCJD. Due to its excellent clinical correlations it has the potential to monitor disease in emerging disease-modifying trials.     

Relationship between baseline brain metabolism measured using [18F]FDG PET and memory and executive function in prodromal and early Alzheimer’s disease

Differences in brain metabolism as measured by FDG-PET in prodromal and early Alzheimer’s disease (AD) have been consistently observed, with a characteristic parietotemporal hypometabolic pattern. However, exploration of brain metabolic correlates of more nuanced measures of cognitive function has been rare, particularly in larger samples. We analyzed the relationship between resting brain metabolism and memory and executive functioning within diagnostic group on a voxel-wise basis in 86 people with AD, 185 people with mild cognitive impairment (MCI), and 86 healthy controls (HC) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We found positive associations within AD and MCI but not in HC. For MCI and AD, impaired executive functioning was associated with reduced parietotemporal metabolism, suggesting a pattern consistent with known AD-related hypometabolism. These associations suggest that decreased metabolic activity in the parietal and temporal lobes may underlie the executive function deficits in AD and MCI. For memory, hypometabolism in similar regions of the parietal and temporal lobes were significantly associated with reduced performance in the MCI group. However, for the AD group, memory performance was significantly associated with metabolism in frontal and orbitofrontal areas, suggesting the possibility of compensatory metabolic activity in these areas. Overall, the associations between brain metabolism and cognition in this study suggest the importance of parietal and temporal lobar regions in memory and executive function in the early stages of disease and an increased importance of frontal regions for memory with increasing impairment.     

Preconditioning with sevoflurane ameliorates spatial learning and memory deficit after focal cerebral ischemia–reperfusion in rats

Previous studies have demonstrated that sevoflurane could attenuate cerebral neuron necrosis and apoptosis in ischemia–reperfusion models in rats. The aim of our study was to investigate the effect of preconditioning with sevoflurane on spatial learning and memory ability after focal cerebral ischemia–reperfusion injury in rats and its potential mechanisms. Focal cerebral ischemia was performed via 1 h of middle cerebral artery occlusion (MCAO) followed by reperfusion. Before ischemia, rats were subjected to preconditioning with inhalation of 2.4% sevoflurane for 1 h. The spatial learning and memory ability of rats was measured by the Morris water maze. The activity of choline acetyltransferase (ChAT) in hippocampus CA1 region was observed by immunohistochemistry method. We found MCAO elicited a significant decrease of the ability of spatial learning and memory in contrast to the sham surgery controls. However, preconditioning with sevoflurane resulted in significantly ameliorates spatial learning and memory deficit induced by MCAO. Furthermore, the number of ChAT positive cells in hippocampus CA1 region in sevoflurane preconditioning group was striking more than that of ischemia–reperfusion group. All results suggested that preconditioning with 2.4% sevoflurane could ameliorate the ability of spatial learning and memory after focal cerebral ischemia–reperfusion in rats via protecting the cholinergic neurons in hippocampal CA1 region.     

Can memory and executive functions in patients with obsessive–compulsive disorder predict outcome of cognitive behavioural therapy?

Background: Most studies find that patients with obsessive–compulsive disorder (OCD) have impaired memory and executive functions. Cognitive behavioural therapy (CBT) is the recommended psychotherapeutic treatment of patients with OCD. We hypothesized that impairments in memory and executive functions would predict poor outcome of CBT. Aim: To investigate whether memory and executive functions in patients with OCD could predict outcome of CBT. Methods: We assessed 39 patients with OCD before CBT with neuropsychological tests of memory and executive functions, the Hamilton Depression Rating Scale, and the Global Assessment of Functioning Scale. Furthermore, we assessed severity of OCD symptoms before and after CBT using the Yale–Brown Obsessive Compulsive Scale. Results: There were no statistically significant differences between recovered (41%) and non-recovered patients (59%) on any neuropsychological test variables or on any baseline demographic variables. Furthermore, change in OCD symptoms was not predicted by neuropsychological test performances or baseline severity of OCD symptoms. The only statistically significant finding was that non-recovered patients had lower social functioning before CBT than recovered patients (p = 0.018, d = 0.797). Conclusions: Memory and executive functions in patients with OCD could not predict outcome of CBT, but level of social functioning may be a predictor of CBT outcome. Some of the main clinical implications are that we cannot use memory and executive functions, or baseline severity of OCD symptoms to determine which patients should be offered CBT.     

Dysregulation of the sympathetic nervous system,hypothalamic–pituitary–adrenal axis and executive function in individuals at risk for suicide

Background

Suicidal behaviour aggregates in families, and the hypothalamic–pituitary–adrenal (HPA) axis and noradrenergic dysregulation may play a role in suicide risk. It is unclear whether stress dysregulation is a heritable trait of suicide or how it might increase risk. We investigated stress reactivity of the autonomic nervous system and the HPA axis in suicide predisposition and characterized the effect of this dysregulation on neuropsychologic function.

Methods

In this family-based study of first-degree relatives (n = 14) of suicide completers and matched controls with no family or personal history of suicidal behaviour (n = 14), participants underwent the Trier Social Stress Test (TSST). We used salivary α-amylase and cortisol levels to characterize stress reactivity and diurnal variation. We administered a series of neuropsychologic and executive function tests before and after the TSST.

Results

Despite normal diurnal variation, relatives of suicide completers exhibited blunted cortisol and α-amylase TSST reactivity. Although there were no baseline differences in conceptual reasoning, sustained attention or executive function, the relatives of suicide completers did not improve on measures of inhibition upon repeated testing after TSST. Secondary analyses suggested that these effects were related to suicide vulnerability independent of major depression.

Limitations

The sample size was small, and the design prevents us from disentangling our findings from the possible traumatic consequences of losing a relative by suicide.

Conclusions

Blunted stress response may be a trait of suicide risk, and impairment of stress-induced executive function may contribute to suicide vulnerability.