Perceived stress modulates the activity between the amygdala and the cortex.

The significant link between stress and psychiatric disorders has prompted research on stress's impact on the brain. Interestingly, previous studies on healthy subjects have demonstrated an association between perceived stress and amygdala volume, although the mechanisms by which perceived stress can affect brain function remain unknown. To better understand what this association entails at a functional level, herein, we explore the association of perceived stress, measured by the PSS10 questionnaire, with disseminated functional connectivity between brain areas. Using resting-state fMRI from 252 healthy subjects spanning a broad age range, we performed both a seed-based amygdala connectivity analysis (static connectivity, with spatial resolution but no temporal definition) and a whole-brain data-driven approach to detect altered patterns of phase interactions between brain areas (dynamic connectivity with spatiotemporal information). Results show that increased perceived stress is directly associated with increased amygdala connectivity with frontal cortical regions, which is driven by a reduced occurrence of an activity pattern where the signals in the amygdala and the hippocampus evolve in opposite directions with respect to the rest of the brain. Overall, these results not only reinforce the pathological effect of in-phase synchronicity between subcortical and cortical brain areas but also demonstrate the protective effect of counterbalanced (i.e., phase-shifted) activity between brain subsystems, which are otherwise missed with correlation-based functional connectivity analysis.

Association of amygdala size with stress perception: Findings of a transversal study across the lifespan.

Daily routines are getting increasingly stressful. Interestingly, associations between stress perception and amygdala volume, a brain region implicated in emotional behaviour, have been observed in both younger and older adults. Life stress, on the other hand, has become pervasive and is no longer restricted to a specific age group or life stage. As a result, it is vital to consider stress as a continuum across the lifespan. In this study, we investigated the relationship between perceived stress and amygdala size in 272 healthy participants with a broad age range. Participants were submitted to a structural magnetic resonance imaging (MRI) to extract amygdala volume, and the Perceived Stress Scale (PSS) scores were used as the independent variable in volumetric regressions. We found that perceived stress is positively associated with the right amygdala volume throughout life.

A novel method for estimating connectivity-based parcellation of the human brain from diffusion MRI: Application to an aging cohort.

Connectivity-based parcellation (CBP) methods are used to define homogenous and biologically meaningful parcels or nodes-the foundations of brain network fingerprinting-by grouping voxels with similar patterns of brain connectivity. However, we still lack a gold standard method and the use of CBPs to study the aging brain remains scarce. Our study proposes a novel CBP method from diffusion MRI data and shows its potential to produce a more accurate characterization of the longitudinal alterations in brain network topology occurring in aging. For this, we constructed whole-brain connectivity maps from diffusion MRI data of two datasets: an aging cohort evaluated at two timepoints (mean interval time: 52.8 ± 7.24 months) and a normative adult cohort-MGH-HCP. State-of-the-art clustering techniques were used to identify the best performing technique. Furthermore, we developed a new metric (connectivity homogeneity fingerprint [CHF]) to evaluate the success of the final CBP in improving regional/global structural connectivity homogeneity. Our results show that our method successfully generates highly homogeneous parcels, as described by the significantly larger CHF score of the resulting parcellation, when compared to the original. Additionally, we demonstrated that the developed parcellation provides a robust anatomical framework to assess longitudinal changes in the aging brain. Our results reveal that aging is characterized by a reorganization of the brain's structural network involving the decrease of intra-hemispheric, increase of inter-hemispheric connectivity, and topological rearrangement. Overall, this study proposes a new methodology to perform accurate and robust evaluations of CBP of the human brain.

Habitual coffee drinkers display a distinct pattern of brain functional connectivity.

Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive effects of this methylxanthine. Interestingly, the effects of its chronic consumption on the brain's intrinsic functional networks are still largely unknown. This study provides the first extended characterization of the effects of chronic coffee consumption on human brain networks. Subjects were recruited and divided into two groups: habitual coffee drinkers (CD) and non-coffee drinkers (NCD). Resting-state functional magnetic resonance imaging (fMRI) was acquired in these volunteers who were also assessed regarding stress, anxiety, and depression scores. In the neuroimaging evaluation, the CD group showed decreased functional connectivity in the somatosensory and limbic networks during resting state as assessed with independent component analysis. The CD group also showed decreased functional connectivity in a network comprising subcortical and posterior brain regions associated with somatosensory, motor, and emotional processing as assessed with network-based statistics; moreover, CD displayed longer lifetime of a functional network involving subcortical regions, the visual network and the cerebellum. Importantly, all these differences were dependent on the frequency of caffeine consumption, and were reproduced after NCD drank coffee. CD showed higher stress levels than NCD, and although no other group effects were observed in this psychological assessment, increased frequency of caffeine consumption was also associated with increased anxiety in males. In conclusion, higher consumption of coffee and caffeinated products has an impact in brain functional connectivity at rest with implications in emotionality, alertness, and readiness to action.

Reorganization of brain structural networks in aging: A longitudinal study.

Normal aging is characterized by structural and functional changes in the brain contributing to cognitive decline. Structural connectivity (SC) describes the anatomical backbone linking distinct functional subunits of the brain and disruption of this communication is thought to be one of the potential contributors for the age-related deterioration observed in cognition. Several studies already explored brain network's reorganization during aging, but most focused on average connectivity of the whole-brain or in specific networks, such as the resting-state networks. Here, we aimed to characterize longitudinal changes of white matter (WM) structural brain networks, through the identification of sub-networks with significantly altered connectivity along time. Then, we tested associations between longitudinal changes in network connectivity and cognition. We also assessed longitudinal changes in topological properties of the networks. For this, older adults were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24). WM structural networks were derived from diffusion magnetic resonance imaging, and cognitive status from neurocognitive testing. Our results show age-related changes in brain SC, characterized by both decreases and increases in connectivity weight. Interestingly, decreases occur in intra-hemispheric connections formed mainly by association fibers, while increases occur mostly in inter-hemispheric connections and involve association, commissural, and projection fibers, supporting the last-in-first-out hypothesis. Regarding topology, two hubs were lost, alongside with a decrease in connector-hub inter-modular connectivity, reflecting reduced integration. Simultaneously, there was an increase in the number of provincial hubs, suggesting increased segregation. Overall, these results confirm that aging triggers a reorganization of the brain structural network.

Applicability of the Telephone Interview for Cognitive Status (Modified) in a community sample with low education level: association with an extensive neuropsychological battery.

OBJECTIVE: To explore the applicability of a Portuguese (PT) version of the Telephone Interview for Cognitive Status (TICS), with a delayed recall item [modified (M)], here termed TICSM-PT, against an extensive (in-person) battery of neuropsychological instruments, in a sample of older individuals with low educational level and without clinically manifest/diagnosed cognitive impairment. METHODS: Following translation/back-translation and pilot testing in 33 community dwellers, 142 community dwellers aged 52 to 84 years (mean = 67.45, SD = 7.91) were selected from local health care centres for the study (convenience sampling; stratified age and gender). Cronbach's alpha was used to assess internal consistency, and convergent validity was evaluated through the correlation between TICSM-PT and the Mini Mental State Examination (MMSE), as well as with a comprehensive battery of cognitive instruments. Divergent/discriminant validity was assessed through a battery of psychological instruments. The receiver operating curve was determined for TICSM-PT to classify participants with and without possible indication of cognitive impairment. RESULTS: TICSM-PT showed a satisfactory internal consistency (Cronbach's alpha = 0.705), convergent validity and discriminant validity. TICSM-PT presented a positive association with the global cognitive measures Mini Mental State Examination and the Montreal Cognitive Assessment, and also with most neuropsychological parameters. Receiver operating curve curves presented a sensitivity of 90.6% and specificity of 73.7%. The area under the curve statistic yielded a threshold score equal or below 13.5 for cognitive impairment. CONCLUSION: TICSM-PT is a practical tool for rapid cognitive assessment among older individuals with low educational background.

Physiological and behavioral contagion/buffering effects of chronic unpredictable stress in a socially enriched environment: A preliminary study.

Rodents are sensitive to the emotional state of conspecifics. While the presence of affiliative social partners mitigates the physiological response to stressors (buffering), the partners of stressed individuals show behavioral and endocrine changes indicating that stress parameters can be transmitted across the group members (contagion). In this study, we investigated the social contagion/buffering phenomena in behavior and neuroendocrine mechanisms after exposure to chronic stress, in groups of rats living in the PhenoWorld (PhW). Three groups were tested (8 stressed rats, 8 unstressed rats, and a mixed group with 4 and 4) and these were analyzed under 4 conditions: stressed (pure stress group, n = 8), unstressed (naive control group, n = 8), stressed from mixed group (stressed companion group, n = 8), unstressed from mixed group (unstressed companion group, n = 8. While naive control animals remained undisturbed, pure stress group animals were all exposed to stress. Half of the animals under the mixed-treatment condition were exposed to stress (stressed companion group) and cohabitated with their unstressed partners (unstressed companion group). We confirmed the well-established chronic unpredictable stress (CUS) effects in physiological, behavioral, and neuroendocrine endpoints; body weight gain, open arm entries and time in EPM, and oxytocin receptor expression levels in the amygdala decreased by stress exposure, whereas adrenal weight was increased by stress. Furthermore, we found that playing, rearing and solitary resting behaviors decreased, whereas huddling behavior increased by CUS. In addition, we detected significant increases (stress-buffering) in body weight gain and huddling behaviors between pure stress and stress companion animals, and significant stress contagion effects in emotional behavior and oxytocin receptor expression levels between naive control and control companion groups. Hence, we demonstrate buffering and contagion effects were evident in physiological parameters, emotional behaviors, and social home-cage behaviors of rats and we suggest a possible mediation of these effects by oxytocin neurotransmission. In conclusion, the results herein suggest that the stress status of animals living in the same housing environment influences the behavior of the group.

Home-cage behavior is impacted by stress exposure in rats.

Being social animals, rats exhibit a range of social behaviors that help them build social bonds and maintain group cohesion. Behavior is influenced by multiple factors, including stress exposure, and the expression of the impact of stress on both social and non-social behaviors may also be affected by the living conditions of rats. In this study, we explored the physiological and behavioral effects of chronic unpredictable stress on group-housed rats in the PhenoWorld (PhW), a socially and physically enriched environment closer to real-life conditions. Two independent experiments were performed: one in the control condition (PhW control, n = 8) and one in the stress condition (PhW stress, n = 8). Control animals remained undisturbed except for cage cleaning and daily handling procedures. Stress group animals were all exposed to chronic unpredictable stress. Data confirm that stress exposure triggers anxiety-like behavior in the PhW. In terms of home-cage behaviors, we found that stress affects social behaviors (by decreased playing and increased huddling behaviors) and non-social behaviors (as shown by the decrease in rearing and walking behaviors). These results are of relevance to expand our knowledge on the influence of stress on social and non-social behaviors, which are of importance to understand better species-typical behaviors.

Coffee consumption decreases the connectivity of the posterior Default Mode Network (DMN) at rest.

Habitual coffee consumers justify their life choices by arguing that they become more alert and increase motor and cognitive performance and efficiency; however, these subjective impressions still do not have a neurobiological correlation. Using functional connectivity approaches to study resting-state fMRI data in a group of habitual coffee drinkers, we herein show that coffee consumption decreased connectivity of the posterior default mode network (DMN) and between the somatosensory/motor networks and the prefrontal cortex, while the connectivity in nodes of the higher visual and the right executive control network (RECN) is increased after drinking coffee; data also show that caffeine intake only replicated the impact of coffee on the posterior DMN, thus disentangling the neurochemical effects of caffeine from the experience of having a coffee.

Shaping social behavior in an enriched environment.

Access to vital needs shapes social orders. In rats, social systems tend to maintain a certain stability, but alterations in the physical environment can change inter-individual relations, which consequently can alter social orders. Principles governing social systems are, however, difficult to study and most analyses have been restricted to dyads of animals over short periods of time, hardly capturing the complexity and temporal dynamics of social interactions. Herein, we studied social interactions in a colony of six rats living in a customized enriched environment (PhenoWorld, PhW), under variable conditions of access/availability to limited resources. Reductions in food accessibility and availability resulted in a marked heterogeneity in sniffing, chasing and fighting/struggling behaviors, and, in the latter condition, an overall increase of these displays. The introduction of the possibility of interaction with a female rat also increased the amount of sniffing and fighting/struggling in a homogeneous manner. Results also showed that individual food retrieval success had no association with fighting/struggling when food pellets are delivered to the animals. However, there was a statistically significant correlation between fighting/struggling and impulsivity as measured by the amount of premature responses in the Variable-to-Signal-Test outside of the PhW providing external validation to our measures. To sum up, through continuous monitoring of a group of rats in the PhW, we demonstrated how variations in access to reinforcers modulate social behavior.

Prevalence and Characterisation of Patients with Asthma According to Disease Severity in Portugal: Findings from the EPI-ASTHMA Pilot Study.

Objective: To assess the feasibility of the procedures of EPI-ASTHMA. EPI-ASTHMA is a population-based multicentre stepwise study about the prevalence and characterisation of patients with asthma based on disease severity in Portugal. Methods: A pilot study of EPI-ASTHMA was conducted with adults from three primary care centres. We followed a stepwise approach comprising 4 stages: stage 0-invitation phone call (n ~1316); stage 1-telephone interview (n ~658); stage 2-clinical assessment with physical examination, diagnostic tests, and patient-reported outcome measures, to confirm the diagnosis of those with possible asthma at stage 1 (n ~160); stage 3-characterization of a subgroup of asthma patients by collecting data through a telephone interview, patient file review and CARATm app (n ~40), after 3-months. The frequency of asthma was calculated in relation to the entire study population (stage 1) and the frequency of difficult-to-treat/severe asthma in relation to the number of asthma patients (stage 3). Results: From 1305 adults invited, 892 (68%) accepted to participate (stage 0) and 574 (64%; 53[42-67] y; 43% male) were interviewed (stage 1). From those, 148 (26%; 60[46-68] y; 43% male) were assessed at stage 2, and 46 (31%; 51[39-67] y; 44% male) were diagnosed with asthma. Half of these patients (n = 23) accepted to install the app. Stage 3 was completed by 41 (93%) patients, of whom 31 (83%) had asthma confirmed by their file review. A total of 8% of participants had asthma, of those 17% had difficult-to-treat and 5% severe asthma. Conclusion: Attained recruitment rates and the quality of the results confirmed the feasibility of the EPI-ASTHMA stepwise approach. This pilot study provided insight into the improvement of the procedures to be generalized across the country.

EPI-ASTHMA study protocol: a population-based multicentre stepwise study on the prevalence and characterisation of patients with asthma according to disease severity in Portugal.

INTRODUCTION: In Portugal as in other countries, data on the epidemiology of asthma are mainly grounded in questionnaire studies. Additionally, the detailed characterisation of asthma in terms of disease severity, control and phenotypes remain scarce. Studies assessing the prevalence of asthma and its subgroups using accurate methods are needed. This study aims to determine the prevalence of asthma, difficult-to-treat asthma and severe asthma, and to evaluate sociodemographic and clinical characteristics of those patients, in mainland Portugal. METHODS AND ANALYSIS: A population-based nationwide study with a multicentre stepwise approach will be conducted between 2021 and 2023 in 38 primary care centres of the Portuguese National Health Service. The stepwise approach will comprise four stages: Stage 0-telephone call invitation to adult subjects (≥18 years) randomly selected (n~15 000); stage 1-telephone screening interview assessing the participants' respiratory symptoms (n~7500); stage 2-diagnostic visit, including physical examination, diagnostic tests (eg, spirometry, fraction of exhaled nitric oxide, blood eosinophil count) and patient-reported outcome measures for diagnostic confirmation of those identified with possible asthma at stage 1 (n~1800); stage 3-further evaluation of patients with asthma and of patients with difficult-to-treat asthma and severe asthma, after 3 months (n~460). At stage 3, data will be collected from a review of the patient's electronic health records, a follow-up telephone call and the CARATm (Caracteristicas Auto-reportadas de Asma em Tecnologias Móveis) app database. The prevalence of asthma, difficult-to-treat asthma and severe asthma will be determined as the percentage of patients with asthma confirmed from the overall population (stage 1). For the analysis of factors associated with asthma, difficult-to-treat asthma and severe asthma, logistic regression models will be explored. ETHICS AND DISSEMINATION: Ethical approvals for the study were obtained from the ethics committee of the local health unit of Matosinhos, Porto (38/CES/JAS), Alto Minho (38/2021/CES) and the regional health administration of Lisbon-Vale do Tejo (035/CES/INV/2021). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05169619.

Amygdala size varies with stress perception.

Stress is inevitably linked to life. It has many and complex facets. Notably, perception of stressful stimuli is an important factor when mounting stress responses and measuring its impact. Indeed, moved by the increasing number of stress-triggered pathologies, several groups drew on advanced neuroimaging techniques to explore stress effects on the brain. From that, several regions and circuits have been linked to stress, and a comprehensive integration of the distinct findings applied to common individuals is being pursued, but with conflicting results. Herein, we performed a volumetric regression analysis using participants' perceived stress as a variable of interest. Data shows that increased levels of perceived stress positively associate with the right amygdala and anterior hippocampal volumes.

Signatures of white-matter microstructure degradation during aging and its association with cognitive status.

Previous studies have shown an association between cognitive decline and white matter integrity in aging. This led to the formulation of a "disconnection hypothesis" in the aging-brain, which states that the disruption in cortical network communication may explain the cognitive decline during aging. Although some longitudinal studies have already investigated the changes occurring in white matter microstructure, most focused on specific white matter tracts. Our study aims to characterize the longitudinal whole-brain signatures of white matter microstructural change during aging. Furthermore, we assessed the relationship between distinct longitudinal alterations in white matter integrity and cognition. White matter microstructural properties were estimated from diffusion magnetic resonance imaging, and cognitive status characterized from extensive neurocognitive testing. The same individuals were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24) between first and last assessment. Our results show that age is associated with a decline in cognitive performance and a degradation in white matter integrity. Additionally, significant associations were found between diffusion measures and different cognitive dimensions (memory, executive function and general cognition). Overall, these results suggest that age-related cognitive decline is related to white matter alterations, and thus give support to the "disconnected hypothesis" of the aging brain.

The Association of Metabolic Dysfunction and Mood Across Lifespan Interacts With the Default Mode Network Functional Connectivity.

Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study. Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied. Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmetabolism, lipids imbalance, and blood pressure. Using multiple linear regression models, this study observed that metabolic dysfunction, glucose dysmetabolism, and lipids imbalance were linearly associated with depressive mood, and the association with obesity was U-shaped. The association of metabolic dysfunction, obesity, and glucose dysmetabolism with depressive mood is positive for the younger individuals in our sample and vanishes with aging. The FC of the right superior temporal gyrus with the DMN correlated with both obesity and depressive mood. In participants with higher obesity scores, FC increased with higher GDS scores, while in those with lower GDS scores, FC decreased. Age and blood pressure were associated with a more complex pattern of association between FC of the right supramarginal gyrus and GDS score. Conclusion: The association of metabolic dysfunction with depressive mood is influenced by age and relates with differential patterns of DMN-FC. The combination of the effects of age, mood, and metabolic dysfunction is likely to explain the heterogeneity of DMN-FC, which deserves further investigation with larger and longitudinal studies.

Higher Adherence to the Mediterranean Diet Is Associated With Preserved White Matter Integrity and Altered Structural Connectivity.

The Mediterranean diet (MedDiet) has been associated with cognitive performance. Yet, controlled trials have yielded contradictory results. To tackle this controversy, a comprehensive multimodal analysis of the association of the MedDiet with cognitive performance and brain structure in normative aging is still necessary. Here, community dwellers ≥50 years from a cohort study on normative aging (n = 76) underwent a (i) magnetic resonance imaging session with two acquisitions: structural and diffusion-weighted imaging (DWI); (ii) neuropsychological battery of tests focusing on memory and executive functioning; and (iii) dietary assessment through the Mediterranean Diet Assessment Screener (MEDAS, score range: 0-14, scores ≥10 indicate high adherence to the Mediterranean diet) 18 months prior to the brain imaging and neuropsychological assessment. We found that high adherence to the MedDiet (MEDAS ≥10) was associated with higher values of fractional anisotropy and lower diffusivity values in the brain white matter. Similarly, high adherence to the MedDiet was associated with higher structural connectivity between left hemisphere brain regions. Specifically, the amygdala, lingual, olfactory, middle occipital gyrus, and calcarine areas. No association was found between high adherence to the MedDiet and total brain volumes or hypointensities. Higher adherence to the MedDiet was positively associated with executive functioning scores. These results suggest that high adherence to the MedDiet positively associates with brain health, specifically with executive function scores and white matter integrity of bundles related to the processing and integration of taste, reward, and decision making. These findings seem to support the view that the MedDiet should be part of recommendations to promote a healthy brain.

Iron Status is Associated with Mood, Cognition, and Functional Ability in Older Adults: A Cross-Sectional Study.

Several conditions are risk factors for iron deficiency (ID), some of which are highly prevalent in older individuals. Despite the amount of evidence pointing for a role of ID in cognition, mood and physical functional ability, the research addressing these associations in older individuals is still scarce. In the present study, 162 older community-dwelling individuals (29.53% classified as ID) were enrolled in a cross-sectional analysis and characterized regarding cognition, mood, functional ability, general nutritional intake and iron status. Assessment of iron status was performed using several blood biomarkers. Storage and erythropoiesis dimensions were positively associated with memory, along with an interaction (moderator effect) between iron storage and nutritional status. A more depressed mood was negatively associated with (iron) transport, transport saturation and erythropoiesis dimensions, and functional tiredness was positively associated with the erythropoiesis dimension. These observations indicate that lower iron status is associated with depressive mood, functional tiredness and poorer memory ability, with the latter moderated by nutritional status. These findings suggest that using iron as a continuous variable may be useful in finding associations with iron homeostasis, eventually missed when iron levels are considered within the usual classification groups.

Asymmetrical subcortical plasticity entails cognitive progression in older individuals.

Structural brain asymmetries have been associated with cognition. However, it is not known to what extent neuropsychological parameters and structural laterality covary with aging. Seventy-five subjects drawn from a larger normal aging cohort were evaluated in terms of MRI and neuropsychological parameters at two moments (M1 and M2), 18 months apart. In this time frame, asymmetry as measured by structural laterality index (ΔLI) was stable regarding both direction and magnitude in all areas. However, a significantly higher dispersion for this variation was observed in subcortical over cortical areas. Subjects with extreme increase in rightward lateralization of the caudate revealed increased M1 to M2 Stroop interference scores, but also a worsening of general cognition (MMSE). In contrast, subjects showing extreme increase in leftward lateralization of the thalamus presented higher increase in Stroop interference scores. In conclusion, while a decline in cognitive function was observed in the entire sample, regional brain asymmetries were relatively stable. Neuropsychological trajectories were associated with laterality changes in subcortical regions.

Longitudinal measurement invariance of memory performance and executive functioning in healthy aging.

In this work, we examined the longitudinal measurement invariance of a battery composed of distinct cognitive parameters. A sample of 86 individuals (53.5% females; mean age = 65.73), representative of the Portuguese older population, with respect to sex, age and level of education was assessed twice over an average of two years. By means of a confirmatory factor analysis approach, we tested whether a two-factor solution [corresponding to measures of memory performance (MEM) and executive functioning (EXEC)] was reliable over time. Nested models of longitudinal invariance demonstrated the existence of partial strong invariance over time. In other words, this indicates that there is an equivalence of the factorial structure and factor loadings for all items; this was also observed for the item intercepts for all the items, except for one of the items from the EXEC dimension. Stability coefficients revealed high associations between the dimensions over time and that, whereas there was a significant decline of the MEM across time, this was not observed for the EXEC dimension. These findings reveal that changes in MEM and EXEC scores can be attributed to true changes on these constructs, enabling the use of this battery as a reliable method to study cognitive aging.

Poor Sleep Quality Associates With Decreased Functional and Structural Brain Connectivity in Normative Aging: A MRI Multimodal Approach.

Sleep is a ubiquitous phenomenon, essential to the organism homeostasis. Notwithstanding, there has been an increasing concern with its disruption, not only within the context of pathological conditions, such as neurologic and psychiatric diseases, but also in health. In fact, sleep complaints are becoming particularly common, especially in middle-aged and older adults, which may suggest an underlying susceptibility to sleep quality loss and/or its consequences. Thus, a whole-brain modeling approach to study the shifts in the system can cast broader light on sleep quality mechanisms and its associated morbidities. Following this line, we sought to determine the association between the standard self-reported measure of sleep quality, the Pittsburgh Sleep Quality Index (PSQI) and brain correlates in a normative aging cohort. To this purpose, 86 participants (age range 52-87 years) provided information regarding sociodemographic parameters, subjective sleep quality and associated psychological variables. A multimodal magnetic resonance imaging (MRI) approach was used, with whole-brain functional and structural connectomes being derived from resting-state functional connectivity (FC) and probabilistic white matter tractography (structural connectivity, SC). Brain regional volumes and white matter properties associations were also explored. Results show that poor sleep quality was associated with a decrease in FC and SC of distinct networks, overlapping in right superior temporal pole, left middle temporal and left inferior occipital regions. Age displayed important associations with volumetric changes in the cerebellum cortex and white matter, thalamus, hippocampus, right putamen, left supramarginal and left lingual regions. Overall, results suggest that not only the PSQI global score may act as a proxy of changes in FC/SC in middle-aged and older individuals, but also that the age-related regional volumetric changes may be associated to an adjustment of brain connectivity. These findings may also represent a step further in the comprehension of the role of sleep disturbance in disease, since the networks found share regions that have been shown to be affected in pathologies, such as depression and Alzheimer's disease.