Proper Cognitive Function Research Articles

Impaired Hippocampal Long-Term Potentiation and Memory Deficits upon Haploinsufficiency of MDGA1 Can Be Rescued by Acute Administration of D-Cycloserine.

The maintenance of proper brain function relies heavily on the balance of excitatory and inhibitory neural circuits, governed in part by synaptic adhesion molecules. Among these, MDGA1 (MAM domain-containing glycosylphosphatidylinositol anchor 1) acts as a suppressor of synapse formation by interfering with Neuroligin-mediated interactions, crucial for maintaining the excitatory-inhibitory (E/I) balance. Mdga1-/- mice exhibit selectively enhanced inhibitory synapse formation in their hippocampal pyramidal neurons, leading to impaired hippocampal long-term potentiation (LTP) and hippocampus-dependent learning and memory function; however, it has not been fully investigated yet if the reduction in MDGA1 protein levels would alter brain function. Here, we examined the behavioral and synaptic consequences of reduced MDGA1 protein levels in Mdga1+/- mice. As observed in Mdga1-/- mice, Mdga1+/- mice exhibited significant deficits in hippocampus-dependent learning and memory tasks, such as the Morris water maze and contextual fear-conditioning tests, along with a significant deficit in the long-term potentiation (LTP) in hippocampal Schaffer collateral CA1 synapses. The acute administration of D-cycloserine, a co-agonist of NMDAR (N-methyl-d-aspartate receptor), significantly ameliorated memory impairments and restored LTP deficits specifically in Mdga1+/- mice, while having no such effect on Mdga1-/- mice. These results highlight the critical role of MDGA1 in regulating inhibitory synapse formation and maintaining the E/I balance for proper cognitive function. These findings may also suggest potential therapeutic strategies targeting the E/I imbalance to alleviate cognitive deficits associated with neuropsychiatric disorders.

Ad libitum dehydration is associated with poorer performance on a sustained attention task but not other measures of cognitive performance among middle-to-older aged community-dwelling adults: A short-term longitudinal study.

Hydration status and water intake are critical to physiological health. Despite a popular narrative that dehydration impairs cognitive performance, results are mixed in the literature. Therefore, we tested how hydration status was associated with cognitive performance in an ad libitum state over the course of 3 months. Data come from a short-term longitudinal study among middle-to-older aged US adults (n = 78) measured three times (207 observations). All participants were scheduled for 8:00 a.m. visits for the baseline, two-week, and 3-month examinations where they completed surveys, neuropsychological tests to measure cognitive performance, anthropometrics, and a blood draw for biomarker analysis. Serum osmolality (Sosm) was measured as a biomarker of hydration status using osmometry. Four cognitive performance tasks were assessed, including inhibition, working memory, cognitive flexibility, and sustained attention. Panel random effects linear regressions demonstrate that there was an inverse association between dehydration and sustained attention, whereas there were no significant relationships between dehydration and inhibition, working memory, and cognitive flexibility. Adults who were dehydrated (defined as Sosm >300 mOsm/kg) performed substantially worse (B = 0.65 z-score; SE = 0.28; p = .020) on the sustained attention task than those who were not dehydrated adjusting for time fixed effects, age, body mass index, sex, and educational attainment. This short-term longitudinal study found that dehydration was only associated with poorer performance on a cognitive performance task that required sustained attention. Maintaining adequate hydration may be increasingly important for middle-to-older aged adults to ensure proper cognitive function, particularly as water needs increase in future climatic scenarios.

Association between Body Iron Status and Cognitive Task Performance in a Nationally Representative Sample of Older Adults.

Iron is an essential micronutrient that is necessary for proper cognitive function. However, the dose-response relationship between body iron status and cognitive function remains unclear. The objective of this study was to investigate the association between serum ferritin concentrations, an indicator of body iron status, and cognitive function in older adults. Based on the National Health and Nutrition Examination Survey (NHANES) 1999 -2002 in the United States, nationally representative data was collected from 2,567 adults aged 60 years and older who had objectively measured serum ferritin levels and cognitive performance. High ferritin levels were defined as a serum ferritin level >200 ng/mL in women and >300 ng/mL in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL. The digit symbol substitution test (DSST) was employed to assess cognitive function. Multivariable logistic regression analyses with survey weights were performed after the DSST was dichotomized at the median score. The weighted prevalence of adults with normal, low, and high serum ferritin levels were 73.98%, 9.12%, and 16.91%, respectively. A U-shaped association between serum ferritin concentrations and cognitive task performance was observed. After adjusting for demographic, socioeconomic, lifestyle, and C-reactive protein factors, the odds ratio (95% confidence intervals) for lower cognitive performance was 1.39 (1.11, 1.74) in adults with high ferritin levels and 1.38 (0.86, 2.22) in adults with low ferritin levels, compared with those with normal ferritin levels. The association between serum ferritin levels and lower cognitive performance was stronger in adults aged 60 to 69 years old than those aged 70 years and older. In conclusion, in a nationally representative sample of older adults in the United States, a high serum ferritin level was significantly associated with worse cognitive task performance. Thus, the relationship between low serum ferritin concentrations and cognitive task performance warrants further investigation.

COGNITIVE AGEING BETWEEN CUMULATIVE EFFECT OF LIFESTYLE AND CATCH-UP COGNITIVE INTERVENTIONS

Normal neurocognitive aging is characterized by its selective effect on the damaged neuronal regions and at the cognitive level. This heterogeneous nature constituted a strong motive for deepening the research on the causes of the emergence of interindividual cognitive differences within the same age group, helped by functional brain imaging techniques. The study starts from this premise and aims to shed light on the concept of "successful aging" from a neurocognitive perspective. This concept is at the center of attention of many researchers in various disciplines as it is related to two basic concepts: The firs concept is "brain reserve." It is related to people’s lifestyle, and is built and accumulated over the course of life through people's behaviours that are neurologically, and cognitively (reserve indicators) stimulated. The second concept is "Overdue reserve”. It is related to intensive cognitive interventions (indicators of Overdue reserve), as a catch-up and efficient mechanism that enables people with low levels of brain reserve to stimulate neuroplasticity, which contributes to enhance their cognitive performance. This study aims to explore the appropriate conditions, and effective ways, to help people develop functional neurological resistance against the decline that characterizes human cognition with advancing age. Hence, maintaining proper cognitive functioning contributes to improving the quality of life of seniors as well as enabling them to age healthily: psychologically, cognitively, and socially.

Decoding Natural Astrocyte Rhythms: Dynamic Actin Waves Result from Environmental Sensing by Primary Rodent Astrocytes.

Astrocytes are key regulators of brain homeostasis, equilibrating ion, water, and neurotransmitter concentrations and maintaining essential conditions for proper cognitive function. Recently, it has been shown that the excitability of the actin cytoskeleton manifests in second-scale dynamic fluctuations and acts as a sensor of chemophysical environmental cues. However, it is not known whether the cytoskeleton is excitable in astrocytes and how the homeostatic function of astrocytes is linked to the dynamics of the cytoskeleton. Here it is shown that homeostatic regulation involves the excitable dynamics of actin in certain subcellular regions of astrocytes, especially near the cell boundary. The results further indicate that actin dynamics concentrate into "hotspot" regions that selectively respond to certain chemophysical stimuli, specifically the homeostatic challenges of ion or water concentration increases. Substrate topography makes the actin dynamics of astrocytes weaker. Super-resolution images demonstrate that surface topography is also associated with the predominant perpendicular alignment of actin filaments near the cell boundary, whereas flat substrates result in an actin cortex mainly parallel to the cell boundary. Additionally, coculture with neurons increases both the probability of actin dynamics and the strength of hotspots. The excitable systems character of actin thus makes astrocytes direct participants in neural cell network dynamics.

Community support and promoting cognitive function for the elderly.

Proper cognitive functions are critical to the life of the elderly. With the rapid aging of the population, community support plays an important role in cognitive functioning. This study examines the association between community support and the level of cognitive functioning in the elderly, and the mediating effect of social participation in the relationship. Based on the panel data of China Longitudinal Healthy Longevity Survey (CLHLS) in 2005, 2008, 2011, 2014, and 2018, people aged 65 and over are selected as the research object (N = 35,479). The panel Logit model is used to analyze the influence of community support on their cognitive functioning. In addition, the stepwise regression and KHB decomposition methods are used to test the influence mechanism of community support on their cognitive function. The benchmark regression results show that there is a significant correlation between community support and cognitive function in the elderly (OR: 1.64, 95% CI: 1.41–1.91, p < 0.01). Daily care (OR: 1.75, 95% CI: 1.33–2.29, p < 0.01) has the strongest impact on the cognitive function of the elderly, followed by health care (OR: 1.70, 95% CI: 1.43–2.01, p < 0.01) and legal support (OR: 1.64, 95% CI: 1.37–1.95, p < 0.01), while psychological care (OR: 1.62, 95% CI: 1.31–2.01, p < 0.01) has the weakest impact on the cognitive function of the elderly. The results of the mediation effect test show that social participation plays a significant intermediary role in the impact of community support on the cognitive function of the elderly (mediation percentage: 16.89%), demonstrating that community support can improve the cognitive function of the elderly by promoting the social participation of the elderly. In classified community support, social participation plays a significant intermediary role in the impact of psychological care on cognition (mediation percentage: 46.10%).

Effects of Five Amino Acids (Serine, Alanine, Glutamate, Aspartate, and Tyrosine) on Mental Health in Healthy Office Workers: A Randomized, Double-Blind, Placebo-Controlled Exploratory Trial

Background: The importance of maintaining good mental health with overall well-being has recently drawn attention from various spheres of academics and the working population. Amino acid intake has been reported to reduce depression symptoms and other mental health problems. However, the effectiveness of amino acid intake (i.e., single or combined) remains unknown. In this study, we assessed a combination of five amino acids (serine, alanine, glutamate, aspartate, and tyrosine; SAGAT) reported to regulate mental health. Methods: A randomized, double-blind, placebo-controlled exploratory trial was conducted. Participants, aged between 20 and 65 years with fatigue sensation, were randomized to receive either SAGAT or the placebo and ingested them for four weeks. A transient mental work was loaded at day 0 and after four weeks of intervention. As the primary outcomes, the fatigue sensation was assessed. The mood status, cognitive function, work efficiency, and blood marker were also measured as secondary outcomes. Results: The number of participants analyzed for the efficacy evaluation were 20 in SAGAT and 22 in the placebo. There were no significant differences in the primary outcomes. However, as the secondary outcomes, the SAGAT group showed a significant improvement in motivation and cognitive function in the recovery period after mental work loaded in a four-week intervention compared to the placebo. Conclusion: The current findings suggest that SAGAT contributes to maintaining proper motivation and cognitive function. Clinical Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (ID: UMIN 000041221).

Choline Intake Correlates with Cognitive Performance among Elder Adults in the United States.

Objective This research attempted to explore the neuroprotective effect of choline and establish evidence for future dietary recommendations and nutritional interventions to maintain a proper cognitive function among elders aged >60 years in the US. Method This cross-sectional study retrieved data of 2,393 eligible elderly participants from the 2011-2014 National Health and Nutrition Examination Survey. Combining dietary and supplement choline intake, total choline intake was evaluated using the 24-hour dietary recall method and the dietary supplement questionnaire. Total choline intake was categorized into tertiles, which ranged at <187.60 mg/day (T1), 187.60-399.50 mg/day (T2), and >399.50 mg/day (T3). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, Animal Fluency (AF) test, and Digit Symbol Substitution test (DSST) was used to measure cognitive function. Participants who scored the lowest 25th percentile in each cognitive test were classified in the low cognitive function (LC) group. Logistic regression models were implemented to examine the association between total choline intake and the incidence of LC. Results In the CERAD test, the risk of LC was significantly lower in T2 than T1 (OR: 0.668, 95% CI: 0.493-0.904, and P = 0.006) when adjusted for age, gender, BMI, alcohol consumption, and hypertension. Similarly, T2 was associated with a significantly lower risk of LC when assessed by the AF test (OR: 0.606, 95% CI: 0.580-0.724, and P < 0.001) and DSST (0.584, 95% CI: 0.515-0.661, and P < 0.001). In all three cognitive measures, the T3 of the total choline intake was not associated with cognitive function compared to T1. Conclusion Total choline intake at 187.06-399.50 mg/day reduces the risk of LC by approximately 50% compared to intake at <187.6 mg/day. The findings of this research may be used to establish dietary recommendations and nutritional interventions to optimize the cognitive function among elders.

Working memory, attention and their relationship: A theoretical overview

It is broadly agreed that working memory and attention constitute two significant cognitive skills that are closely related. Their relationship has been proved to be intertwined and has attracted intense research interest. It is worth noting that, due to the growth of cognitive neuroscience and neuroimaging studies, there have been many fruitful steps towards further interpreting this link between working memory and attention. In this article, there has been an attempt to explore the concept of working memory and attention and delineate several theoretical options for conceptualizing their relationship. Furthermore, in this article, many neuroscientific aspects of working memory, attention, and their relationship are presented to inform the readers about these concepts and motivate them to deepen their understanding of working memory and attention. Simultaneously, the present article highlights the importance of working memory, attention, and their relationship for the individuals’ proper cognitive function and, generally, their function and attitude in daily life.

On the relationship between tinnitus distress, cognitive performance and aging.

In this study we analyzed psychometric data of 107 individuals who suffer from chronic subjective tinnitus. In particular, we elucidated the relationship between tinnitus-related distress, psychological comorbidities, age, and hearing, and the performance in cognitive concentration and interference tests. Previous research has provided first evidence that individuals with tinnitus may have deficits in cognitive tasks. The present study aimed at extending former research by investigating the relationship between tinnitus distress and cognition. Statistical analyses comprised correlation and regression approaches. We observed a significant relationship between tinnitus distress (tinnitus score, TQ), age and hearing loss and the performance in tests on selective and sustained attention (d2 test) and cognitive interference (Stroop test). Tinnitus distress was identified as the most important predictor of cognitive performance (additionally age for cognitive interference). For other psychometric variables (perceived stress, PSQ; self-efficacy, optimism and pessimism, SWOP) and hearing loss we could not find any meaningful relationship with cognitive performance. The results clearly point to a (currently non-causal) relationship between cognitive skills and distress of tinnitus-related symptoms. Furthermore, the influence of age is noteworthy as this finding implies that with increasing age an appropriate coping with aversive tinnitus symptoms based on proper cognitive functions and age-related hearing dysfunctions, namely inhibition, may become more difficult. Hence, it is suggested to consider cognitive tests as a supplementary measurement in clinical assessment of tinnitus and to raise awareness for the impairing influence of tinnitus on cognition in daily life.

Evaluation of Cognitive Function in Trials Testing New-Generation Hormonal Therapy in Patients with Prostate Cancer: A Systematic Review.

Simple SummaryIn patients with prostate cancer, the use of new-generation hormonal therapy, added to androgen deprivation therapy, requires careful evaluation of cognitive function. The aim of this systematic review is to describe the evidence about cognitive function in randomized trials testing new-generation hormonal therapy (abiraterone, enzalutamide, apalutamide, darolutamide). For each trial, we assessed the availability of both investigator-assessed cognitive impairment and disorders and patient-reported evaluation of cognitive function. Out of 19 trials, the investigator-based evaluation of cognitive impairment was available in seven (36.8%), while patient-reported evaluation of cognitive function results was presented only in one trial (5.3%). This analysis shows that, despite cognitive deterioration could be relevant in patients with prostate cancer, clinical development of new-generation hormonal drugs has not included a systematic evaluation of cognitive function.In patients with prostate cancer, earlier use and longer duration of new-generation hormonal therapy (NGHT), added to androgen deprivation therapy, requires careful evaluation of cognitive function. The aim of this systematic review is to describe the evidence about cognitive function in all the randomized trials (RCTs) testing NGHT (abiraterone, enzalutamide, apalutamide, darolutamide). We assessed the availability of both investigator-assessed cognitive impairment and disorders and patient-reported evaluation of cognitive function. Nineteen RCTs (17,617 patients) were included. The investigator-based evaluation of cognitive impairment was available in seven RCTs (36.8%). In total, 19/19 RCTs (100%) included patient-reported outcomes (PROs) collection, but PRO tools adopted allowed evaluation of cognitive function in two RCTs (10.5%). Among them, PRO-based cognitive function results were presented only in one RCT (5.3%): in ENZAMET, mean changes from baseline were worse with enzalutamide than with placebo, but deterioration-free survival favored enzalutamide. Despite cognitive deterioration could be relevant, clinical development of NGHT has not included a systematic evaluation of cognitive function. Assessment by investigators is at risk of underreporting, and commonly used PROs do not allow proper cognitive function analysis. Furthermore, the methodology of analysis can jeopardize the interpretation of results. Although direct comparisons are scanty, there could be differences between different NGHTs.

Rac1 Impairs Forgetting-Induced Cellular Plasticity in Mushroom Body Output Neurons.

Active memory forgetting is a well-regulated biological process thought to be adaptive and to allow proper cognitive functions. Recent efforts have elucidated several molecular players involved in the regulation of olfactory forgetting in Drosophila, including the small G protein Rac1, the dopamine receptor DAMB, and the scaffold protein Scribble. Similarly, we recently reported that dopaminergic neurons mediate both learning- and forgetting-induced plasticity in the mushroom body output neuron MBON-γ2α′1. Two open questions remain: how does forgetting affect plasticity in other, highly plastic, mushroom body compartments and how do genes that regulate forgetting affect this cellular plasticity? Here, we show that forgetting reverses short-term synaptic depression induced by aversive conditioning in the highly plastic mushroom body output neuron MBON-γ1pedc>α/β. In addition, our results indicate that genetic tampering with normal forgetting by inhibition of small G protein Rac1 impairs restoration of depressed odor responses to learned odor by intrinsic forgetting through time passing and forgetting induced acutely by shock stimulation after conditioning or reversal learning. These data further indicate that some forms of forgetting truly erase physiological changes generated by memory encoding.

Electroencephalographic Cross-Frequency Coupling as a Sign of Disease Progression in Patients With Mild Cognitive Impairment: A Pilot Study.

Mild cognitive impairment (MCI) refers to mild objective cognitive deficits and is associated with the later development of Alzheimer’s disease (AD). However, not all patients with MCI convert to AD. EEG spectral power has shown promise as a marker of progression, but brain oscillations in different frequencies are not isolated entities. Coupling between different frequency bands, so-called cross-frequency coupling (CFC), has been associated with memory function and may further contribute to our understanding of what characterizes patients with MCI who progress to AD. In the current study, we wanted to investigate the changes in gamma/theta CFC in patients with AD and MCI compared to HC and in patients with pMCI compared to patients with sMCI. Furthermore, we wanted to investigate the association with cognitive test scores. EEGs were included at baseline for 15 patients with AD, 25 patients with MCI, and 36 older HC, and the participants were followed for up to 3 years. To investigate CFC, we calculated the modulation index (MI), which has been shown to be less affected by noisy data compared to other techniques. We found that patients with pMCI showed a significantly lower global gamma/theta CFC compared to patients with sMCI. In addition, global gamma/theta CFC was significantly correlated with Addenbrooke’s Cognitive Examination (ACE) score (p-value = 0.030, rho = 0.527). Although not significant, patients with AD and MCI showed a lower gamma/theta CFC compared to HC. These findings suggest that gamma/theta CFC is important for proper cognitive functioning and that a decrease in gamma/theta CFC in patients with MCI may be a sign of progression. Gamma/theta CFC may therefore serve as a progression marker in MCI, but larger studies are needed to validate these findings.

The protective effect of alpha lipoic acid (ALA) on social interaction memory, but not passive avoidance in sleep-deprived rats.

Sleep is involved in maintaining energy, regulating heat, and recovering tissues. Furthermore, proper cognitive functions need sufficient sleep. Many studies have revealed the impairment effect of sleep deprivation (SD) on cognitive functions including learning and memory. Alpha lipoic acid (ALA) is a potent free radical scavenger, biological antioxidant, and neuroprotective agent. Furthermore, ALA improves learning and memory performance, decreases oxidative stress, and enhances antioxidant biomarkers. In this study, we aimed to investigate the effect of ALA on social interaction and passive avoidance memories in sleep-deprived rats. Total sleep deprivation (TSD) apparatus was used to induce SD (for 24h). Three-chamber paradigm test and shuttle box apparatus were used to evaluate social interaction and passive avoidance memory, respectively. Rats' locomotor apparatus was used to assess locomotion. ALA was administered intraperitoneally at doses of 17 and 35mg/kg for 3 consecutive days. The results showed SD impaired both types of memories. ALA at the dose of 35mg/kg restored social interaction memory in sleep-deprived rats; while, at the dose of 17mg/kg attenuated impairment effect of SD. Moreover, ALA at the dose of 35mg/kg impaired passive avoidance memory in sham-SD rats and at both doses did not rescue passive avoidance memory in sleep-deprived rats. In conclusion, ALA showed impairment effect on passive avoidance memory, while improved social interaction memory in sleep-deprived rats.

Activation and Inactivation of Nicotinic Receptnors in the Dorsal Hippocampal Region Restored Negative Effects of Total (TSD) and REM Sleep Deprivation (RSD) on Memory Acquisition, Locomotor Activity and Pain Perception

Sleep deprivation (SD) is a common issue in today’s society. Sleep is essential for proper cognitive functions, including learning and memory. Furthermore, sleep disorders can alter pain information processing. Meanwhile, hippocampal nicotinic receptors have a role in modulating pain and memory. The goal of this study is to investigate the effect of dorsal hippocampal (CA1) nicotinic receptors on behavioral changes induced by Total (TSD) and REM Sleep Deprivation (RSD). A modified water box and multi-platform apparatus were used to induce TSD and RSD, respectively. To investigate the interaction between nicotinic receptors and hippocampus-dependent memory, nicotinic receptor agonist (nicotine) or antagonist (mecamylamine) was injected into the CA1 region. The results showed, nicotine at the doses of 0.001 and 0.1 µg/rat and mecamylamine at the doses of 0.01 and 0.1 µg/rat decreased memory acquisition, while both at the doses of 0.01 and 0.1 µg/rat enhanced locomotor activity. Additionally, all doses used for both drugs did not alter pain perception. Also, 24 h TSD or RSD attenuated memory acquisition with no effect on locomotor activity and only TSD induced an analgesic effect. Intra-CA1 administration of subthreshold dose of nicotine (0.0001 µg/rat) and mecamylamine (0.001 µg/rat) did not alter memory acquisition, pain perception and locomotor activity in sham of TSD/RSD rats. Both drugs reversed all behavioral changes induced by TSD. Furthermore, both drugs reversed the effect of RSD on memory acquisition, while only mecamylamine reversed the effect of RSD on locomotor activity. In conclusion, CA1 nicotinic receptors play a significant role in TSD/RSD-induced behavioral changes.

De la telaraña a la web: Artefactos cognitivos en animales no-humanos

We examine the notion of cognitive artifact and its possible application to the animal technic. Although the issue of animal technic is not very much discussed, the case studies focused on the capacity of using and manufacturing tools suggest that some animals deploy cognitive skills. Could the tools employed by animals be considered genuine cases of cognitive artifacts? In this paper we propose a definition of “cognitive artifact” based on the notion of “proper function,” which allows us to develop a gradual scale where we place different kinds of artifacts according to the prevalence of the cognitive function (in opposition to the practical one). Applying this scale to the non-human sphere, we defend the idea that there exists a range of non-human technical phenomena of use and artifacts and tools manufacturing, and that some of this artifacts have an incipient proper cognitive function. In order to defend these theses, we examine the examples of the cobwebs, the nests and the honeycombs.

The dopaminergic receptors control the availability of the NMDA receptor co-agonist d-serine to enable proper synaptic activity and cognitive function

The dopaminergic receptors control the availability of the NMDA receptor co-agonist d-serine to enable proper synaptic activity and cognitive function

Self efficacy in sleep disorder patients

Sleep, a complex biologic process controlled by the nervous system and is important for proper cognitive, immune and metabolic function. As the aging occurs, it leads to changes in sleep, and the prevalence of sleep disorders increases with age, having a negative impact on the quality of life and well being in older adults.The present study was aimed to examine the effect of sleep disorder on self efficacy of adults. The sample consisted of 240 patients, 120 sleep disorder and 120 non-sleep disorder patients. Test of sleep disorder screening questionnaire by Emory Health Care Centre and Academic Medical College Atlanta, Georgia and self efficacy by Pareek (1988) were used. For analysis of data Mean, SD and t test were used. Results revealed that patients with sleep disorder have poor self efficacy in comparison to normal adults. Patients with Insomnia sleep disorder have better self efficacy in comparison to other types of sleep disorder patients.

Medical and Research Consent Decision-Making Capacity in Patients with Alzheimer's Disease: A Systematic Review.

The capacity to make decisions is an important feature of daily living, which is closely linked to proper cognitive functioning. In conditions in which cognitive functioning becomes compromised, such as in Alzheimer's disease (AD), decision-making capacity can also get affected. Especially in AD, this has important implications, since over the course of the condition many important clinical decisions have to be made. For caregivers as well as physicians, it is sometimes difficult to determine how and when to intervene in the decision-making process. The aim of this systematic literature review was to identify studies that have evaluated medical and research consent decision-making capacity in patients with AD. Studies consistently show that decision-making capabilities are impaired in patients with AD. The cognitive and neuronal correlates of this process are, however, poorly studied. The few studies that investigated correlations have shown worse cognitive performance, mainly on the MMSE, to be related to poorer decision-making capacity. As most of these correlations have been performed in groups combining patients and controls, it remains unknown if these associations are disease specific. There is a need to study more systematically the decision-making process in relation to cognitive functioning and neural correlates to be able to develop a framework of decision-making capacity in AD, ultimately aiding clinicians and caregivers to understand and evaluate those capabilities in patients.

Molecular profiling of reticular gigantocellularis neurons indicates that eNOS modulates environmentally dependent levels of arousal

Neurons of the medullary reticular nucleus gigantocellularis (NGC) and their targets have recently been a focus of research on mechanisms supporting generalized CNS arousal (GA) required for proper cognitive functions. Using the retro-TRAP method, we characterized transcripts enriched in NGC neurons which have projections to the thalamus. The unique expression and activation of the endothelial nitric oxide (eNOS) signaling pathway in these cells and their intimate connections with blood vessels indicate that these neurons exert direct neurovascular coupling. Production of nitric oxide (NO) within eNOS-positive NGC neurons increases after environmental perturbations, indicating a role for eNOS/NO in modulating environmentally appropriate levels of GA. Inhibition of NO production causes dysregulated behavioral arousal after exposure to environmental perturbation. Further, our findings suggest interpretations for associations between psychiatric disorders and mutations in the eNOS locus.