Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Larger dlPFC and vmPFC grey matter volumes are associated with high adherence to the Mediterranean diet: A cross-sectional study in older adults.

Dietary self-control is associated with inter-individual differences in neuroanatomy. Yet, whether such inter-individual differences are also associated with healthier dietary patterns is yet to be determined. In this cross-sectional study, a total of 100 northern Portuguese older community-dwellers were assessed with regards to i) the adherence to a healthy dietary eating pattern - the Mediterranean diet (MedDiet), and ii) grey matter density (GMD) of brain regions associated with valuation and dietary self-regulation, the ventromedial (vmPFC) and dorsolateral prefrontal cortex (dlPFC), through voxel-based morphometry. Healthy food choices were ascertained through the Mediterranean Diet Adherence Screener (MEDAS) where higher scores indicated greater adherence to the MedDiet. Voxel-based morphometry showed that greater grey matter density in the dlPFC and vmPFC associated with a higher adherence to the MedDiet. These results replicate previous links between dietary decision-making measured under laboratory conditions and the neuroanatomy of the brain's valuation and self-control system. Importantly, they shed new light on the potential relevance of inter-individual differences in the neuroanatomy of these two brain regions for adhering to healthier dietary patterns in everyday life.

Promoting Digital Proficiency and Health Literacy in Middle-aged and Older Adults Through Mobile Devices With the Workshops for Online Technological Inclusion (OITO) Project: Experimental Study.

BACKGROUND: Digital inclusion and literacy facilitate access to health information and can contribute to self-care behaviors and informed decision-making. However, digital literacy is not an innate skill, but rather requires knowledge acquisition. OBJECTIVE: The present study aimed to develop, conduct, and measure the impact, on digital and health literacy, of a digital inclusion program aimed at community dwellers. METHODS: The program targeted the recruitment of people aged 55 and older that owned mobile devices with an internet connection in 3 cities in northern Portugal (Paredes de Coura, Guimarães, and Barcelos). The program was titled the Workshops for Online Technological Inclusion (OITO) project and, in each city, was promoted by the coordinator of municipal projects and organized as an in-person 8-workshop program, using mobile devices, smartphones, or tablets. A quasi-experimental design was used with a nonrandomized allocation of participants in each set of 8 workshops. Sociodemographic, health status, and mobile use information were collected at baseline. Digital and health literacy were measured via the Mobile Device Proficiency Questionnaire and the Health Literacy Scale questionnaires, respectively, at baseline (T1), program completion (T2), and a 1-month follow-up (T3). A self-reported measure of autonomy was evaluated at T1 and T2 using a visual scale. RESULTS: Most participants were women with primary schooling (up to 4 years) aged between 65 and 74 years and retired. The intervention had an 81% (97/120) recruitment rate, 53% (43/81) adherence, and 94% (67/71) satisfaction rate, with 81 participants completing the entire 8-workshop program. Most participants had owned their mobile device for more than one year (64/81, 79%), were frequent daily users (70/81, 86%), and had received their mobile device from someone else (33/64, 52%). Over 80% (71/81) of the participants who completed the intervention used Android smartphones. At baseline, participants had low baseline scores in digital literacy, but medium-high baseline scores in health literacy. They showed significant improvement in digital literacy at T2 and T3 compared to T1, but without a significant difference between T2 and T3, regardless of sex, age, or schooling. A significant improvement in self-reported autonomy was observed at T3 compared with baseline. Regarding health literacy, no significant differences were found at T2 or T3 compared to the baseline. CONCLUSIONS: The feasibility indicators showed that the OITO project methodology had a substantial rate of recruitment and satisfaction. Program participants had significant improvement in digital literacy after 8 workshops and maintained their score 1 month after completing the intervention. There was no significant change in health literacy during the project period.

Knowledge of Nutrition and Physical Activity Guidelines is Not Associated with Physical Function in Dutch Older Adults Attending a Healthy Ageing Public Engagement Event.

Purpose: Evidence-based guidelines on nutrition and physical activity are used to increase knowledge in order to promote a healthy lifestyle. However, actual knowledge of guidelines is limited and whether it is associated with health outcomes is unclear. Participants and Methods: This inception cohort study aimed to investigate the association of knowledge of nutrition and physical activity guidelines with objective measures of physical function and physical activity in community-dwelling older adults attending a public engagement event in Amsterdam, The Netherlands. Knowledge of nutrition and physical activity according to Dutch guidelines was assessed using customized questionnaires. Gait speed and handgrip strength were proxies of physical function and the Minnesota Leisure Time Physical Activity Questionnaire was used to assess physical activity in minutes/week. Linear regression analysis, stratified by gender and adjusted for age, was used to study the association between continuous and categorical knowledge scores with outcomes. Results: In 106 older adults (mean age=70.1 SD=6.6, years) who were highly educated, well-functioning, and generally healthy, there were distinct knowledge gaps in nutrition and physical activity which did not correlate with one another (R2=0.013, p=0.245). Knowledge of nutrition or physical activity guidelines was not associated with physical function or physical activity. However, before age-adjustment nutrition knowledge was positively associated with HGS in males (B= 0.64 (95% CI: 0.05, 1.22)) and having knowledge above the median was associated with faster gait speed in females (B=0.10 (95% CI: 0.01, 0.19)). Conclusion: Our findings may represent a ceiling effect of the impact knowledge has on physical function and activity in the this high performing and educated population and that there may be other determinants of behavior leading to health status such as attitude and perception to consider in future studies.

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.

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.

The Physical Activity and Nutritional INfluences in Ageing (PANINI) Toolkit: A Standardized Approach towards Physical Activity and Nutritional Assessment of Older Adults.

Assessing multiple domains of health in older adults requires multidimensional and large datasets. Consensus on definitions, measurement protocols and outcome measures is a prerequisite. The Physical Activity and Nutritional INfluences In Ageing (PANINI) Toolkit aims to provide a standardized toolkit of best-practice measures for assessing health domains of older adults with an emphasis on nutrition and physical activity. The toolkit was drafted by consensus of multidisciplinary and pan-European experts on ageing to standardize research initiatives in diverse populations within the PANINI consortium. Domains within the PANINI Toolkit include socio-demographics, general health, nutrition, physical activity and physical performance and psychological and cognitive health. Implementation across various countries, settings and ageing populations has proven the feasibility of its use in research. This multidimensional and standardized approach supports interoperability and re-use of data, which is needed to optimize the coordination of research efforts, increase generalizability of findings and ultimately address the challenges of ageing.

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.

Iodine supplementation: compliance and association with adverse obstetric and neonatal outcomes.

Objectives: Over 1.9 billion people worldwide are living in areas estimated to be iodine insufficient. Strategies for iodine supplementation include campaigns targeting vulnerable groups, such as women in pre-conception, pregnancy and lactation. Portuguese women of childbearing age and pregnant women were shown to be mildly-to-moderately iodine deficient. As a response, in 2013, the National Health Authority (NHA) issued a recommendation that all women considering pregnancy, pregnant or breastfeeding, take a daily supplement of 150-200 µg iodine. This study explored how the iodine supplementation recommendation has been fulfilled among pregnant and lactating women in Portugal, and whether the reported iodine supplements intake impacted on adverse obstetric and neonatal outcomes. Design and methods: Observational retrospective study on pregnant women who delivered or had a fetal loss in the Braga Hospital and had their pregnancies followed in Family Health Units. Results: The use of iodine supplements increased from 25% before the recommendation to 81% after the recommendation. This was mostly due to an increase in the use of supplements containing iodine only. Iodine supplementation was protective for the number of adverse obstetric outcomes (odds ratio (OR) = 0.791, P = 0.018) and for neonatal morbidities (OR = 0.528, P = 0.024) after controlling for relevant confounding variables. Conclusion: The recommendation seems to have succeeded in implementing iodine supplementation during pregnancy. National prospective studies are now needed to evaluate the impact of iodine supplementation on maternal thyroid homeostasis and offspring psychomotor development and on whether the time of the beginning of iodine supplementation (how early during preconception or pregnancy) is relevant to consider.

Usability, Acceptability, and Satisfaction of a Wearable Activity Tracker in Older Adults: Observational Study in a Real-Life Context in Northern Portugal.

BACKGROUND: The use of activity trackers has significantly increased over the last few years. This technology has the potential to improve the levels of physical activity and health-related behaviors in older adults. However, despite the potential benefits, the rate of adoption remains low among older adults. Therefore, understanding how technology is perceived may potentially offer insight to promote its use. OBJECTIVE: This study aimed to (1) assess acceptability, usability, and user satisfaction with the Xiaomi Mi Band 2 in Portuguese community-dwelling older adults in a real-world context; (2) explore the mediating effect of the usability on the relationship between user characteristics and satisfaction; and (3) examine the moderating effect of user characteristics on the relationship between usability and user satisfaction. METHODS: Older adults used the Xiaomi Mi Band 2 over 15 days. The user experience was evaluated through the Technology Acceptance Model 3, System Usability Scale, and User Satisfaction Evaluation Questionnaire. An integrated framework for usability and user satisfaction was used to explore user experience. Statistical data analysis included descriptive data analysis, reliability analysis, confirmatory factor analysis, and mediation and moderation analyses. RESULTS: A sample of 110 older adults with an average age of 68.41 years (SD 3.11) completed the user experience questionnaires. Mean user acceptance was very high-perceived ease of use: 6.45 (SD 0.78); perceptions of external control: 6.74 (SD 0.55); computer anxiety: 6.85 (SD 0.47); and behavioral intention: 6.60 (SD 0.97). The usability was excellent with an average score of 92.70 (SD 10.73), and user satisfaction was classified as a good experience 23.30 (SD 2.40). The mediation analysis confirmed the direct positive effect of usability on satisfaction (ß=.530; P<.01) and the direct negative effect of depression on usability (ß=-.369; P<.01). Lastly, the indirect effect of usability on user satisfaction was higher in individuals with lower Geriatric Depression Scale levels. CONCLUSIONS: Findings demonstrate that the Xiaomi Mi Band 2 is suitable for older adults. Furthermore, the results confirmed usability as a determinant of satisfaction with the technology and extended the existing knowledge about wearable activity trackers in older adults.

Free-Living Physical Activity Measured With a Wearable Device Is Associated With Larger Hippocampus Volume and Greater Functional Connectivity in Healthy Older Adults: An Observational, Cross-Sectional Study in Northern Portugal.

Several studies using neuroimaging techniques have established a positive relationship between physical activity (PA) and brain structure and function in older populations. However, the use of subjective measures of PA and the lack of multimodal neuroimaging approaches have limited the understanding of this association. This study aims to explore the associations between PA and brain structure and function by objectively evaluating PA. Community-dwelling cognitively healthy older adults (without diagnosed cognitive, neurological or degenerative disease) were recruited from local health centers and local gyms. In a cross-sectional design, participants were evaluated regarding cognitive, clinical, anthropometric, physical performance, and lifestyle characteristics. A 3 T magnetic resonance imaging (MRI) was performed for structural and functional brain measures. PA time and level was assessed via a Xiaomi Mi Band 2® worn for 15 consecutive days. Participants (n = 110, after inclusion/exclusion criteria and completion of all evaluations) were 58 females (56%), with an average age of 68.42 years old (SD = 3.12), most were active. Multiple regression analysis revealed that higher time spent in vigorous PA associated with larger left parahippocampal gyrus and right hippocampus volumes. Furthermore, the analysis of the functional connectome indicated a greater functional connectivity (FC) between the frontal gyrus, cingulate gyrus, occipital inferior lobe for light, moderate, and total PA time, and sedentary time associated with lower FC in the same networks. Overall, the structural and functional findings may provide evidence on the relevant association between PA and brain health in aging.

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.

European Portuguese Version of the User Satisfaction Evaluation Questionnaire (USEQ): Transcultural Adaptation and Validation Study.

BACKGROUND: Wearable activity trackers have the potential to encourage users to adopt healthier lifestyles by tracking daily health information. However, usability is a critical factor in technology adoption. Older adults may be more resistant to accepting novel technologies. Understanding the difficulties that older adults face when using activity trackers may be useful for implementing strategies to promote their use. OBJECTIVE: The purpose of this study was to conduct a transcultural adaptation of the User Satisfaction Evaluation Questionnaire (USEQ) into European Portuguese and validate the adapted questionnaire. Additionally, we aimed to provide information about older adults' satisfaction regarding the use of an activity tracker (Xiaomi Mi Band 2). METHODS: The USEQ was translated following internationally accepted guidelines. The psychometric evaluation of the final version of the translated USEQ was assessed based on structural validity using exploratory and confirmatory factor analyses. Construct validity was examined using divergent and discriminant validity analysis, and internal consistency was evaluated using Cronbach α and McDonald ω coefficients. RESULTS: A total of 110 older adults completed the questionnaire. Confirmatory factor analysis supported the conceptual unidimensionality of the USEQ (χ24=7.313, P=.12, comparative fit index=0.973, Tucker-Lewis index=0.931, goodness of fit index=0.977, root mean square error of approximation=0.087, standardized root mean square residual=0.038). The internal consistency showed acceptable reliability (Cronbach α=.677, McDonald ω=0.722). Overall, 90% of the participants reported excellent satisfaction with the Xiaomi Mi Band 2. CONCLUSIONS: The findings support the use of this translated USEQ as a valid and reliable tool for measuring user satisfaction with wearable activity trackers in older adults, with psychometric properties consistent with the original version.

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.

MADRID+90 study on factors associated with longevity: Study design and preliminary data.

The progressive aging of the population represents a challenge for society. In particular, a strong increase in the number of people over 90 is expected in the next two decades. As this phenomenon will lead to an increase in illness and age-related dependency, the study of long-lived people represents an opportunity to explore which lifestyle factors are associated with healthy aging and which with the emergence of age-related diseases, especially Alzheimer's type dementia. The project "Factors associated with healthy and pathologically aging in a sample of elderly people over 90 in the city of Madrid" (MADRID+90) brings together a multidisciplinary research team in neurodegenerative diseases that includes experts in epidemiology, neurology, neuropsychology, neuroimaging and computational neuroscience. In the first phase of the project, a stratified random sampling was carried out according to the census of the city of Madrid followed by a survey conducted on 191 people aged 90 and over. This survey gathered information on demographics, clinical data, lifestyles and cognitive status. Here, the main results of that survey are showed. The second phase of the project aims to characterize individual trajectories in the course of either healthy and pathological aging, from a group of 50 subjects over 90 who will undergo a comprehensive clinical examination comprised of neurological and cognitive testing, MRI and EEG. The ultimate goal of the project is to characterize the biophysical and clinical profiles of a population that tends to receive little attention in the literature. A better understanding of the rapidly increasing group of nonagenarians will also help to design new policies that minimize the impact and future social and economic consequences of rapidly aging societies.

Association between Self-Reported and Accelerometer-Based Estimates of Physical Activity in Portuguese Older Adults.

Accurate assessment of physical activity (PA) is crucial in interventions promoting it and in studies exploring its association with health status. Currently, there is a wide range of assessment tools available, including subjective and objective measures. This study compared accelerometer-based estimates of PA with self-report PA data in older adults. Additionally, the associations between PA and health outcomes and PA profiles were analyzed. Participants (n = 110) wore a Xiaomi Mi Band 2® for fifteen consecutive days. Self-reported PA was assessed using the International Physical Activity Questionnaire (IPAQ) and the Yale Physical Activity Survey (YPAS). The Spearman correlation coefficient was used to compare self-reported and accelerometer-measured PA and associations between PA and health. Bland-Altman plots were performed to assess the agreement between methods. Results highlight a large variation between self-reported and Xiaomi Mi Band 2® estimates, with poor general agreement. The highest difference was found for sedentary time. Low positive correlations were observed for IPAQ estimates (sedentary, vigorous, and total PA) and moderate for YPAS vigorous estimates. Finally, self-reported and objectively measured PA associated differently with health outcomes. Summarily, although accelerometry has the advantage of being an accurate method, self-report questionnaires could provide valuable information about the context of the activity.

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.

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.

Impact of iodine supplementation during preconception, pregnancy and lactation on maternal thyroid homeostasis and offspring psychomotor development: protocol of the IodineMinho prospective study.

BACKGROUND: Iodine deficiency is the most common cause of preventable brain harm and cognitive impairment in children. Portuguese women of childbearing age, pregnant women and their progeny were shown to have inadequate iodine intake. Consequently, the Portuguese Health Authorities have recommended a daily supplementation with 150-200 µg iodine in preconception, pregnancy, and lactation. The IodineMinho study intends to evaluate whether (i) this recommendation impacted on the prevalence of iodine deficiency in pregnant women from the Minho region of Portugal, (ii) the time of initiation of iodine supplementation (if any) influences the serum levels of thyroid hormones at several intervals during pregnancy and (iii) there are serum thyroid-hormone parameters in the 1st trimester of pregnancy that predict psychomotor development of the child at 18 months of age. METHODS: Most Portuguese women are followed throughout pregnancy in community Family Health Units, where family physicians may choose to follow the National recommendation or other, concerning iodine sufficiency. This study will recruit women (N = 304) who intend to become pregnant or are already pregnant from 10 representative Units. Physician's approach and prescriptions, sociodemographic, nutrition and clinical information will be obtained at baseline and throughout pregnancy. To evaluate endocrine function, blood and urine samples will be collected at recruitment, once in each trimester of pregnancy, at delivery and 3 months after delivery. Breastmilk samples will be collected for iodine and energy content analysis. Children will be evaluated for psychomotor development at 18 months. Maternal thyroid volume will be evaluated by ultrasound scan at baseline, in the 3rd trimester and at 3 months after delivery. DISCUSSION: Iodine deficiency early during development precludes children from achieving full intellectual capabilities. This protocol describes a study that is innovative and unique in its detailed and comprehensive evaluation of maternal and child endocrine and psychomotor parameters. By evaluating the effectiveness of the iodine supplementation recommendation, it will contribute to the public health systems' efforts to provide excellence in maternal and infant care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04288531 . Registered 28 February 2020-Retrospectively registered.