Role In Process Research Articles

It Is Written in the Eyes: Inferences From Pupil Size and Gaze Orientation Shape Interpersonal Liking

Research has shown that pupil size shapes interpersonal impressions: Individuals with dilated pupils tend to be perceived more positively than those with constricted pupils. Untested so far is the role of cognitive processes in shaping the effects of pupil size. Two preregistered studies investigated whether the effect of pupil size was qualified by partner's attention allocation inferred from gaze orientation. In Experiment 1 (N = 50) partners with dilated pupils were more liked when gazing toward the participant, but less liked when gazing toward a disliked other. Experiment 2 (N = 50) unveiled the underlying mechanism of the pupil-gaze interplay. Pupillary changes led to inferences about the feelings held by the partner toward the gazed target: Larger pupils signaled positive feelings. Crucially, target identity moderated the response of the participants (i.e., liking toward the partner). This work shows the importance of considering the interplay of affective and cognitive eye-signals when studying person perception.

Muscarinic Receptors Expression in the Peripheral Blood Cells Differentiate Dementia with Lewy Bodies from Alzheimer's Disease.

Central nervous system disruption of cholinergic (ACh) signaling, which plays a major role in cognitive processes, is well documented in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The expression of muscarinic ACh receptors type 1 and 4 (CHRM1 and CHRM4) has been reported to be altered in the brain of DLB patients. We aim to assess the peripheral gene expression of CHRM1 and 4 in DLB as a possible marker as compared to AD and healthy control (HC) subjects. Peripheral blood mononuclear cells were collected from 21 DLB, 13 AD, and 8 HC matched subjects. RT-PCR was performed to estimate gene expression of CHRM1 and CHRM4. Peripheral CHRM1 expression was higher and CHRM4 was lower in DLB and AD compared to HC, whereas both CHRM1 and CHRM4 levels were higher in AD compared to DLB patients. Receiver operating characteristics curves, with logistic regression analysis, showed that combining peripheral CHRM1 and CHRM4 levels, DLB and AD subjects were classified with an accuracy of 76.0%. Alterations of peripheral CHRM1 and CHRM4 was found in both AD and DLB patients as compared to HC. CHRM1 and CHRM4 gene expression resulted to be lower in DLB patients compared to AD. In the future, peripheral CHRM expression could be studied as a possible marker of neurodegenerative conditions associated with cholinergic deficit and a possible marker of response to acetylcholinesterase inhibitors.

Changes in ‘ordinary’ life. Covid-19’s effects on young students’ mental and physical well-being

The present paper builds on the topic of ‘disaster studies’, addressing the most crucial theoretical aspects of them: a) the purpose of studying «meaningful interactions» between the social system and the individuals and their actions; b) the conviction that, in cases of a pandemic or natural disasters, pain and tragedy can take on unequalled levels of emergency, generating powerful effects as relates to the rhythms of ‘ordinary’ life; c) the role of cognitive processes in conditioning daily life and determining individual predispositions towards the future. From this perspective, the research explores the results obtained from an online survey conducted in 2021 on all Sapienza’s students, who have spent an academic mobility period outside Italy or inside Rome. The analysis explores variations and influences of the cognitive-emotional dimension (beliefs, desires, opportunities) on the (intention-to-) action dimension (attitudes, actions), especially considering the physical and mental well-being aspects.

Muscarinic receptor expression in the peripheral blood cells differentiates DLB from AD

Central Nervous System (CNS) disruption of cholinergic (Ach) signaling, which plays a major role in cognitive processes, is well documented in Dementia with Lewy Bodies (DLB) and Alzheimer’s disease (AD) (1,2). The expression of muscarinic Ach receptors type 1 and 4 (CHRM1 and CHRM14) have been reported to be altered in the brain of DLB patients (3). The aim of the present study was to assess the peripheral expression of CHRM1 and CHRM4 in DLB as compared to AD subjects.

Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach.

Background: Recent studies have discovered that functional connections are impaired among patients with Alzheimer's disease (AD), even at the preclinical stage. The cerebellum has been implicated as playing a role in cognitive processes. However, functional connectivity (FC) among cognitive sub-regions of the cerebellum in patients with AD and mild cognitive impairment (MCI) remains to be further elucidated.Objective: Our study aims to investigate the FC changes of the cerebellum among patients with AD and MCI, compared to healthy controls (HC). Additionally, we explored the role of cerebellum FC changes in the cognitive performance of all subjects.Materials: Resting-state functional magnetic resonance imaging (rs-fMRI) data from three different groups (28 AD patients, 26 MCI patients, and 30 HC) was collected. We defined cerebellar crus II and lobule IX as seed regions to assess the intragroup differences of cortico-cerebellar connectivity. Bias correlational analysis was performed to investigate the relationship between changes in FC and neuropsychological performance.Results: Compared to HC, AD patients had decreased FC within the caudate, limbic lobe, medial frontal gyrus (MFG), middle temporal gyrus, superior frontal gyrus, parietal lobe/precuneus, inferior temporal gyrus, and posterior cingulate gyrus. Interestingly, MCI patients demonstrated increased FC within inferior parietal lobe, and MFG, while they had decreased FC in the thalamus, inferior frontal gyrus, and superior frontal gyrus. Further analysis indicated that FC changes between the left crus II and the right thalamus, as well as between left lobule IX and the right parietal lobe, were both associated with cognitive decline in AD. Disrupted FC between left crus II and right thalamus, as well as between left lobule IX and right parietal lobe, was associated with attention deficit among subjects with MCI.Conclusion: These findings indicate that cortico-cerebellar FC in MCI and AD patients was significantly disrupted with different distributions, particularly in the default mode networks (DMN) and fronto-parietal networks (FPN) region. Increased activity within the fronto-parietal areas of MCI patients indicated a possible compensatory role for the cerebellum in cognitive impairment. Therefore, alterations in the cortico-cerebellar FC represent a novel approach for early diagnosis and a potential therapeutic target for early intervention.

Reflexive Rejection: Confessions of our first encounters with SenseMaker®, an emerging research methodology for STEM education

Point of view (25-50 words):
 We are four female educational practitioners who engage in varying degrees and forms of teaching, research, and evaluation. And, we have been educated in legacy research methods. We are curious about new approaches to conceptualizing, inquiring into, and doing science, technology, engineering and math (‘STEM’) education that have the potential to disrupt systemic social, economic, and ecological abuse and exploitation.
 
 Value of submission (25-50 words): This autoethnographic analysis of our individual narratives serves as a cautionary tale and emotional sign-posts for those seeking to explore emerging research methodologies, particularly those that are suited for complex, dynamic social systems, such as “engineering education”: expect cognitive and/or emotional dissonance. By definition, alternative approaches to research will occur as new and possibly foreign to those trained in traditional research approaches. Such a reflexive rejection happens unconsciously and undermines the goal of learning--discovery.
 
 
 Abstract
 It is becoming increasingly common to hear engineering education described as a complex system (National Science Foundation, 2018). Such a perspective shifts the focus of analysis from the parts to the whole – from individual elements to the relationships between the elements. Most engineering education researchers, however, are trained in atomistic or reductionist models of inquiry (Borrego, 2007; Laszlo, 1996; Robbins, 2007), which begs the question – how prepared are engineering education researchers to conduct research on, and productively intervene in, complex systems? As four educational practitioners who have previously embraced complex systems thinking, both in our teaching and in our research, we considered ourselves well prepared to explore a new, participatory research methodology, called SenseMaker, which is explicitly designed to understand characterize and facilitate interventions in complex systems. And yet, all four of us independently and reflexively rejected this methodology upon our first encounter with it. In this study, we used collaborative autoethnographic techniques to examine what it is about our shared cultures, experiences, and training as engineering education researchers and practitioners that led us to react in this way. We reflect on how methodologies founded on complex systems theory, like SenseMaker, often sit outside the boundaries of what we are used to and may initially occur to us as “foreign,” or even “wrong.” Further, we explore how our reflexive responses were connected to embodied cognition, that is, a recognition that “[one’s] body, beyond the brain “play[s] a significant causal… role in cognitive processing” (Stanford Encyclopedia of Philosophy, 2011). We offer some suggestions for developing an awareness of both reflexive rejection responses and how to recognize and use our embodied cognition. These perspectives are important for researchers who seek new ways to understand and work with complex, dynamic social systems.

Profile semantyczne przyjaciela i wroga w polsko-, rosyjsko- i niemieckojęzycznym obrazie świata

The article aims at reconstructing and comparing the cultural meanings contained in the concepts friend and enemy. To achieve the objective, the author referred to research methodologies elaborated by cognitive linguists. Particularly useful were those approaches which emphasize the necessity of including both the role of cognitive processes in descriptions of language and its historical, cultural and social underpinnings. In such approaches, questionnaires and surveys are accepted as sources of empirical data. In the current study, an analysis of the specific connotations attached to the concepts friend and enemy in Polish, German and Russian is performed. The obtained results allow for creating a hierarchy of the criteria that speakers of the three languages take into consideration, and for establishing significant similarities and differences between the Polish, German and Russian semantic profiles of the two concepts.

LDPE/MWCNT and LDPE/MWCNT/UHMWPE self-reinforced fiber-composite foams prepared via supercritical CO2: A microstructure-engineering property perspective

Low-density polyethylene (LDPE)/Multiwall-Carbon-Nanotube (MWCNT) nanocomposites were foamed using supercritical carbon dioxide (CO2). Uniform nanofiller dispersion was assessed by scanning electron microscopy (SEM), rheological measurements, and wide-angle X-ray diffraction (WAXD). By incorporating MWCNTs in the matrix, the average cell size was reduced to less than one-third that of neat foam (from 32.92 to 9.24 µm), and cell density jumped from 0.205 × 109 to 5.26 × 109 cell/cm3. After evaluating the thermal, mechanical, and electrical properties of the nanocomposites and their foams, as well as elucidating the foaming process's role in the crystalline structure, there was a great need to boost the mechanical performance. Hence, ultra-high molecular-weight-polyethylene (UHMWPE) fiber was embedded in the system, which is a reliable reinforcement for, and compatible with, the polyethylene, owing to its basic similarity to the matrix. The electrical conductivity of the solid and foamed materials was greatly improved by the addition of 15 wt% UHMWPE fibers and 1.4 wt% filler.

Executive Functions and Body Weight at Different Ages: A Preliminary Study.

Recently, researchers have focused their attention on the role of cognitive processes on eating habits and body weight changes. Few studies have examined the relationship between the first stages of overweight and executive functions (EFs), excluding obesity conditions. This study is aimed to detect the involvement of the EFs and their predictive role on body mass index (BMI) in a sample of healthy individuals from childhood to young adulthood with a cross-sectional design. One-hundred and sixty-six healthy students were recruited from different Italian public schools: 46 children (age range: 7–11), 50 adolescents (age range: 15–18), 70 young adults (age range: 19–30). BMI was used to evaluate body weight and different EFs tasks were used to assess the EFs domains of inhibition, updating and shifting. After adjusting BMI for age, a hierarchical multiple linear regression was carried out for each EFs task. Pearson’s r correlations were reported for each of the age subgroups. Motor disinhibition was associated with greater BMI in the overall sample. Higher BMI was related to poorer set-shifting in adolescence and poorer motor inhibition in young adulthood, but higher BMI was not associated with EFs in childhood. Differences in the development of EFs over time may influence weight changes over time through different responses to food and eating behavior.

Real-time brain-wide multi-planar microscopy for simultaneous cortex and hippocampus imaging at the cellular resolution in mice.

Interactions between the cerebral cortex and the deep cerebellar nuclei play important roles in cognitive processes. However, conventional microscopes fail to dynamically record cellular structures in distinct brain regions and at different depths, which requires high resolution, large field of view (FOV), and depth of field (DOF). Here we propose a single-photon excited fluorescence microscopy technique that performs simultaneous cortex and hippocampus imaging, enabled by a customized microscope and a chronic optical window. After we implant a glass microwindow above the hippocampus, the surface of the hippocampus is shifted to the superficial plane. We demonstrate that the proposed technique is able to image cellular structures and blood vessel dynamics in the cortex and the hippocampus in in vivo experiments, and is compatible with various mesoscopic systems.

The journey of incumbents’ sustainable business models: unveiling the role of cognitive processes in the evolution process of business models

ABSTRACT There is growing attention in theories and practices to achieve sustainable business models (SBMs). However, achieving SBMs for incumbents is an arduous and challenging process. Based on the literature on SBMs and managerial cognition, we explore how managers use their cognitive processes to adapt business models to environmental changes. Based on the study of a Chinese incumbent, this paper reveals the evolution process of incumbents’ SBMs in the manufacturing sector and indicates managers’ effective cognitive processes under different environmental conditions. This study attempts to open the black box of the link between cognitive processes and SBMs, reveal the role of cognitive heuristics, and provide practice guidance for incumbent firms to achieve sustainable development.

Toward an Embodied, Embedded Predictive Processing Account.

In this paper, I argue for an embodied, embedded approach to predictive processing and thus align the framework with situated cognition. The recent popularity of theories conceiving of the brain as a predictive organ has given rise to two broad camps in the literature that I call free energy enactivism and cognitivist predictive processing. The two approaches vary in scope and methodology. The scope of cognitivist predictive processing is narrow and restricts cognition to brain processes and structures; it does not consider the body-beyond-brain and the environment as constituents of cognitive processes. Free energy enactivism, on the other hand, includes all self-organizing systems that minimize free energy (including non-living systems) and thus does not offer any unique explanations for more complex cognitive phenomena that are unique to human cognition. Furthermore, because of its strong commitment to the mind-life continuity thesis, it does not provide an explanation of what distinguishes more sophisticated cognitive systems from simple systems. The account that I develop in this paper rejects both of these radical extremes. Instead, I propose a compromise that highlights the necessary components of predictive processing by making use of a mechanistic methodology of explanation. The starting point of the argument in this paper is that despite the interchangeable use of the terms, prediction error minimization and the free energy principle are not identical. But this distinction does not need to disrupt the status quo of the literature if we consider an alternative approach: Embodied, Embedded Predictive Processing (EEPP). EEPP accommodates the free energy principle, as argued for by free energy enactivism, but it also allows for mental representations in its explanation of cognition. Furthermore, EEPP explains how prediction error minimization is realized but, unlike cognitivist PP, it allocates a constitutive role to the body in cognition. Despite highlighting concerns regarding cognitivist PP, I do not wish to discredit the role of the neural domain or representations as free energy enactivism does. Neural structures and processes undeniably contribute to the minimization of prediction error but the role of the body is equally important. On my account, prediction error minimization and free energy minimization are deeply dependent on the body of an agent, such that the body-beyond-brain plays a constitutive role in cognitive processing. I suggest that the body plays three constitutive roles in prediction error minimization: The body regulates cognitive activity, ensuring that cognition and action are intricately linked. The body acts as distributor in the sense that it carries some of the cognitive load by fulfilling the function of minimizing prediction error. Finally, the body serves to constrain the information that is processed by an agent. In fulfilling these three roles, the agent and environment enter into a bidirectional relation through influencing and modeling the structure of the other. This connects EEPP to the free energy principle because the whole embodied agent minimizes free energy in virtue of being a model of its econiche. This grants the body a constitutive role as part of the collection of mechanisms that minimize prediction error and free energy. The body can only fulfill its role when embedded in an environment, of which it is a model. In this sense, EEPP offers the most promising alternative to cognitivist predictive processing and free energy enactivism.

Glutamate and Gamma-Aminobutyric Acid Abnormalities in Antipsychotic-Naïve Patients With Schizophrenia: Evidence From Empirical and Meta-analytic Studies Using Magnetic Resonance Spectroscopy

Glutamate and GABA (gamma-aminobutyric acid), the major excitatory and inhibitory neurotransmitters, respectively, play key roles in cognitive processes. Converging evidence from preclinical, postmortem, and human neuroimaging studies indicates that glutamate and GABA are involved in the pathophysiology of psychosis and schizophrenia. Antipsychotic medications used to treat schizophrenia are primarily dopamine antagonists and generally treat the positive symptoms with little effect on cognitive deficits, which can be especially debilitating and lead to poor functional outcomes.

Individual mechanisms underlying peripheral nerve damage when exposed to metallic mercury

Introduction. There is a lack of knowledge of the pathophysiological mechanisms that form peripheral nerve disorders in mercury lesions of professional origin. The study aims to reveal the mechanisms underlying peripheral nerve damage in the long-term post-contact period of chronic mercury intoxication (CMI). Materials and methods. Fifty-one people had the diagnosis of a long-term period of CMI. The post-contact period was 8.5±2.6 years. The authors compared the results with a control group of 26 healthy men who had no contact with toxic substances. Stimulating electroneuromyography was performed. We studied the body systems that could contribute to the formation of disorders in the peripheral nerves. Changes in peripheral hemodynamics were studied using reovasography. The content of autoantibodies, neuron-specific enolase, serotonin, histamine, catecholamines (epinephrine, dopamine), metanephrine, and neurotrophin-3 was reviewed. The content of ceruloplasmin, secondary products of lipid peroxidation processes, reduced glutathione, the activity of superoxide dismutase and the content of nitric oxide levels were determined. Results. The study established pathogenetic structural links of peripheral nerve disorders. The autoimmune process's role was to increase the range of antibodies to the MAG protein and increase the level of antibodies to DNA. Violations of elastic-tonic properties of peripheral vessels could be associated with the functional state of motor axons. The increased content of neurotransmitters is related to the state of peripheral blood circulation; the most pronounced changes were on the legs, which could contribute to the occurrence and maintenance of vasoconstriction. The role of oxidative stress in the formation of demyelinating disorders in patients' peripheral nerves in the long-term period of CRI is possible. Conclusion. Neuroimmunological processes has an essential role in the development of peripheral nerve demyelination was shown, which consists in an increase in the content of antibodies to the MAG protein expressed on Schwann cells of peripheral nerves and in an increase in the level of antibodies to DNA involved in the formation of demyelinating changes when exposed to metallic mercury. The revealed pathological changes in the state of the peripheral blood circulation, characterized by a violation of the vessels' elastic-tonic properties, leading to demyelination of motor axons in patients in the long-term period of CMI. The increased content of neurotransmitters in the examined is of great importance in the state of peripheral circulation. Pronounced changes in blood circulation are established on the lower extremities, which may be associated with the predominance of α-adrenergic receptors in the arterial bed and may contribute to the occurrence and maintenance of vasoconstriction in the legs. The relationship between changes in indicators of oxidative stress, consisting of a decrease in the value of superoxide dismutase and reduced glutathione, and the formation of demyelinating disorders of peripheral nerves in patients in the long-term period of CMI has been proved.

Does cognitive inflexibility predict violent extremist behaviour intentions? A registered direct replication report of Zmigrod, Rentfrow, & Robbins, 2019

PurposeResearch assessing violent extremist risk factors thus far largely ignored the role of cognitive processes. Zmigrod and colleagues (2019a) addressed this gap and presented first systematic evidence that lower levels of cognitive flexibility predict a higher willingness to fight and, ultimately, die for a national ingroup. This finding has important theoretical and practical implications. In order to strengthen the potential contribution of Zmigrod et al.’s work, we will conduct a registered direct replication of Study 1. Extending the original study, we further examine whether the documented relationship still holds when a self‐report measure for cognitive flexibility is introduced and when analyses control for identity fusion. We also investigate if cognitive inflexibility solely predicts violent or also normative pro‐group behaviour intentions.MethodsFollowing Zmigrod, Rentfrow, and Robbins (2019a), we will administer a cross‐sectional survey study. Participants (N = 1,378) report their willingness to fight, die, and sacrifice themselves for the ingroup and complete the Remote Associates as well as Wisconsin Card Sorting tests. Afterwards, additional measures of self‐reported cognitive flexibility, identity fusion, and normative pro‐group behaviour are assessed.ResultsTo be completed.ConclusionsTo be completed.

Modeling Therapeutic Alliance in the Age of Telepsychiatry.

Increasingly, online platforms are being used to deliver psychotherapy. This, along with the growth in computational psychiatry, provides scientists with new opportunities to quantify how patient-therapist relationships relate to treatment outcomes. We argue that it is necessary to investigate markers and mechanisms that enable successful psychotherapy, and the establishment of therapeutic alliance in particular, using computational tools.

Correlates of intelligence via resting-state functional connectivity of the amygdala in healthy adults

Intelligence is a form of advanced cognition that includes reasoning, problem solving, pattern recognition, and establishing relationships among items. The amygdala plays an important role in cognitive processing, but the relationship between amygdalar function and intelligence has rarely been explored directly. Here, we investigated the relationship between resting-state functional connectivity (RSFC) of the amygdala and intelligence test performance in a large sample of healthy adults (N = 197). We found that two pairs of RSFCs were significantly increased in the high IQ group compared with that of the general IQ group. One of these RSFCs consisted of the right amygdala and the right superior parietal lobule, whereas the other RSFC consisted of the right amygdala and the left middle cingulum. In addition, we found that the brain regions in which the strength of RSFC significantly correlated with full IQ (FIQ) were mainly distributed in the parietal and limbic lobes. What’s more, a further mediation analysis indicated that the functional connectivity of the right amygdala and the right superior parietal lobule significantly mediated the correlation between comprehension and object assembly, whereas the functional connectivity of the right amygdala and the left middle cingulum mediated the association between similarities and digit symbol. These findings suggest that amygdalar RSFC may reflect individual differences in intelligence and mediate specific relationships among different intellectual abilities.

The Role of Sleep Quality, Trait Anxiety and Hypothalamic-Pituitary-Adrenal Axis Measures in Cognitive Abilities of Healthy Individuals.

Sleep plays a crucial role in cognitive processes. Sleep and wake memory consolidation seem to be regulated by glucocorticoids, pointing out the potential role of the hypothalamic-pituitary-adrenal (HPA) axis in the relationship between sleep quality and cognitive abilities. Trait anxiety is another factor that is likely to moderate the relationship between sleep and cognition, because poorer sleep quality and subtle HPA axis abnormalities have been reported in people with high trait anxiety. The current study aimed to explore whether HPA axis activity or trait anxiety moderate the relationship between sleep quality and cognitive abilities in healthy individuals. We studied 203 healthy individuals. We measured verbal and visual memory, working memory, processing speed, attention and executive function. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. Trait anxiety was assessed with the State-Trait Anxiety Inventory. HPA axis measures included the cortisol awakening response (CAR), diurnal cortisol slope and cortisol levels during the day. Multiple linear regression analyses explored the relationship between sleep quality and cognition and tested potential moderating effects by HPA axis measures and trait anxiety. Poor sleep quality was associated with poorer performance in memory, processing speed and executive function tasks. In people with poorer sleep quality, a blunted CAR was associated with poorer verbal and visual memory and executive functions, and higher cortisol levels during the day were associated with poorer processing speed. Trait anxiety was a moderator of visual memory and executive functioning. These results suggest that subtle abnormalities in the HPA axis and higher trait anxiety contribute to the relationship between lower sleep quality and poorer cognitive functioning in healthy individuals.

Ghrelin Signaling Affects Feeding Behavior, Metabolism, and Memory through the Vagus Nerve

Vagal afferent neuron (VAN) signaling sends information from the gut to the brain and is fundamental in the control of feeding behavior and metabolism [1]. Recent findings reveal that VAN signaling also plays a critical role in cognitive processes, including affective motivational behaviors and hippocampus (HPC)-dependent memory [2-5]. VANs, located in nodose ganglia, express receptors for various gut-derived peptide signals; however, the function of these receptors with regard to feeding behavior, metabolism, and memory control is poorly understood. We hypothesized that VAN-mediated processes are influenced by ghrelin, a stomach-derived orexigenic hormone, via communication to its receptor (GHSR) expressed on gut-innervating VANs. To examine this hypothesis, rats received nodose ganglia injections of an adeno-associated virus (AAV) expressing short hairpin RNAs targeting GHSR (or a control AAV) for RNAi-mediated VAN-specific GHSR knockdown. Results reveal that VAN GHSR knockdown induced various feeding and metabolic disturbances, including increased meal frequency, impaired glucose tolerance, delayed gastric emptying, and increased body weight compared to controls. Additionally, VAN-specific GHSR knockdown impaired HPC-dependent contextual episodic memory and reduced HPC brain-derived neurotrophic factor expression, but did not affect anxiety-like behavior or general activity levels. A functional role for endogenous VAN GHSR signaling was further confirmed by results revealing that VAN signaling is required for the hyperphagic effects of ghrelin administered at dark onset, and that gut-restricted ghrelin-induced increases in VAN firing rate require intact VAN GHSR expression. Collective results reveal that VAN GHSR signaling is required for both normal feeding and metabolic function as well as HPC-dependent memory.

Amyloidosis increase is not attenuated by long-term calorie restriction or related to neuron density in the prefrontal cortex of extremely aged rhesus macaques.

As human lifespan increases and the population ages, diseases of aging such as Alzheimer's disease (AD) are a major cause for concern. Although calorie restriction (CR) as an intervention has been shown to increase healthspan in many species, few studies have examined the effects of CR on brain aging in primates. Using postmortem tissue from a cohort of extremely aged rhesus monkeys (22-44years old, average age 31.8years) from a longitudinal CR study, we measured immunohistochemically labeled amyloid beta plaques in Brodmann areas 32 and 46 of the prefrontal cortex, areas that play key roles in cognitive processing, are sensitive to aging and, in humans, are also susceptible to AD pathogenesis. We also evaluated these areas for cortical neuron loss, which has not been observed in younger cohorts of aged monkeys. We found a significant increase in plaque density with age, but this was unaffected by diet. Moreover, there was no change in neuron density with age or treatment. These data suggest that even in the oldest-old rhesus macaques, amyloid beta plaques do not lead to overt neuron loss. Hence, the rhesus macaque serves as a pragmatic animal model for normative human aging but is not a complete model of the neurodegeneration of AD. This model of aging may instead prove most useful for determining how even the oldest monkeys are protected from AD, and this information may therefore yield valuable information for clinical AD treatments.