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.

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.

The moderator effect of age in the association between mood and adiposity in the elderly is specific for the subcutaneous adipose compartment: An MRI study.

The positive association between obesity and depressive mood in young- and middle-age individuals is a phenomenon with major clinical implications in public health. Interestingly, the trend of this association in older individuals is not clear, given the conflicting results of multiple studies. Since aging is accompanied by changes in body fat distribution, we questioned whether age is a modulator of such association. This study explores the role of age in the association between mood and general (body mass index [BMI]) and abdominal adiposity (waist circumference [WC]) in older adults characterizing the different abdominal adipose tissue compartments (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]) with magnetic resonance imaging (MRI) techniques. METHODS: One hundred twenty aged community-dwelling individuals (≥50 y of age) were assessed regarding depressive mood (Geriatric Depression Scale) and adiposity (BMI and WC). From these, 96 were assessed for SAT and VAT using MRI. RESULTS: Using multiple linear regression models, depressive mood was positively associated with BMI, WC, and VAT. Age was a significant moderator of the association between depressive mood and BMI, WC, and SAT: positive in younger participants and null or negative in older participants. On the other hand, higher VAT was significantly associated with a more depressive mood, independently of age. CONCLUSIONS: This study identifies age as a relevant moderator in the association between depressive mood and adiposity in the elderlies. Furthermore, the body fat compartment analysis revealed that the effect of age is specific for the SAT, suggesting its protective role in depressive mood.

Discriminant power of socio-demographic characteristics and mood in distinguishing cognitive performance clusters in older individuals: a cross-sectional analysis.

OBJECTIVES: Identification of predictors of cognitive trajectories has been a matter of concern on aging research. For this reason, it is of relevance to infer cognitive profiles based on rapid screening variables in order to determine which individuals will be more predisposed to cognitive decline. METHOD: In this work, a linear discriminant analysis (LDA) was conducted with socio-demographic variables and mood status as predictors of cognitive profiles, computed in a previous sample, based on different cognitive dimensions. Data were randomly split in two samples. Both samples were representative of the Portuguese population in terms of gender, age and education. The LDA was performed with one sample (n = 506, mean age 65.7 ± 8.98 years) and tested in the second sample (n = 548, mean age 68.5 ± 9.3 years). RESULTS: With these variables, we were able to achieve an overall hit rate of 65.9%, which corresponds to a significant increment in comparison to classification by chance. CONCLUSION: Although not ideal, this model may serve as a relevant tool to identify cognitive profiles based on a rapid screening when few variables are available.

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.

The Obsessive-Compulsive Inventory-Revised (OCI-R): Translation and Validation of the European Portuguese Version.

INTRODUCTION: The Obsessive-Compulsive Inventory-Revised has been developed to evaluate the severity of obsessive-compulsive symptoms in both clinical and non-clinical individuals. The aim of this study was to evaluate the psychometric properties of the Portuguese version. MATERIAL AND METHODS: This questionnaire was applied to 90 people with obsessive-compulsive disorder and 246 without a known mental illness. In addition to this clinical evaluation instrument, participants completed other clinical assessment scales that helped characterize the two study groups. RESULTS: Given the objective of this study, to evaluate the structure by six factors, a confirmatory factor analysis was performed [patient group: χ2(120, n = 90) = 205.779, p < 0.01; CFI = 0.916; GFI = 0.814; RMSEA = 0.0890. CONTROL GROUP: χ2(120, n = 246) = 224.762, p < 0.01; CFI = 0.938; GFI = 0.904; RMSEA = 0.060]. To assess the internal consistency of the scale, Cronbach's alpha was determined (patient group: α = 0.913; control group: α = 0.888). Convergent validity was tested by determining the Spearman correlation between the scores obtained in the Obsessive-Compulsive Inventory-Revised and Y-BOCS in the patient group (r = 0.651; p < 0.01). CONCLUSION: Obsessive-Compulsive Inventory-Revised has proved to be a consistent, valid, and reliable instrument with good psychometric properties to determine the severity of obsessive-compulsive symptoms in the Portuguese population.

Introdução: A escala Obsessive-Compulsive Inventory-Revised foi desenvolvida para avaliar a gravidade dos sintomas obsessivo-compulsivos em contexto clínico e não clínico. O objectivo deste estudo foi avaliar as propriedades psicométricas da sua versão portuguesa. Material e Métodos: O questionário em estudo foi aplicado a 90 pessoas com perturbação obsessivo-compulsiva e 246 pessoas sem doença psiquiátrica conhecida. Além deste instrumento de avaliação clínica, os participantes preencheram outras escalas de avaliação clínica que ajudaram a caracterizar os dois grupos de estudo. Resultados: Dado o objetivo deste estudo, para avaliar a estrutura por seis fatores foi realizada uma análise fatorial confirmatória [grupo de doentes: χ2(120, n = 90) = 205,779, p < 0.01; CFI = 0,916; GFI = 0,814; RMSEA = 0,0890. Grupo controlo: χ2(120, n = 246) = 224,762, p < 0,01; CFI = 0,938; GFI = 0,904; RMSEA = 0,060]. Para avaliar a consistência interna da escala foi determinado o alpha de Cronbach (grupo de doentes: α = 0,913. grupo controlo: α = 0,888). A validade convergente foi testada através da determinação da correlação de Spearman entre as pontuações obtidas no Obsessive-Compulsive Inventory-Revised e Y-BOCS no grupo de doentes (r = 0,651; p < 0,01). Conclusão: O Obsessive-Compulsive Inventory-Revised revelou-se um instrumento consistente, válido e fiável com boas propriedades psicométricas para determinar a gravidade dos sintomas obsessivo-compulsivos na população portuguesa.

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.

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.

Applicability and validation of the Reaction to Tests Scale (RTT) in a sample of Portuguese medical students.

BACKGROUND: Test anxiety is a crucial factor in determining academic outcomes, and it may lead to poor cognitive performance, academic underachievement, and psychological distress, interfering specifically with their ability to think and perform during tests. The main objective of this study was to explore the applicability and psychometric properties of a Portuguese version of the Reactions to Tests scale (RTT) in a sample of medical students. METHOD: A sample of 672 medical students completed the RTT. The sample was randomly split in half to allow for independent Exploratory Factor Analysis (EFA) and to test the best fit model-Confirmatory Factor Analysis (CFA). CFA was used to test both the first-order factor structure (four subscales) and second-order factor structure, in which the four subscales relate to a general factor, Test Anxiety. The internal consistency of the RTT was assessed through Cronbach's alpha, Composite reliability (CR) and Average Variance Extracted (AVE) for the total scale and each of the four subscales. Convergent validity was evaluated through the correlation between RTT and the State-Trait Anxiety Inventory (STAI-Y).To explore the comparability of measured attributes across subgroups of respondents, measurement invariance was also studied. RESULTS: Results from exploratory and confirmatory factor analyses showed acceptable fits for the Portuguese RTT version. Concerning internal consistency, results indicate that RTT was found to be reliable to measure test anxiety in this sample. Convergent validity of the RTT with both state and trait anxiety STAI-Y's subscales was also shown. Moreover, multigroup analyses showed metric invariance across gender and curriculum phase. CONCLUSION: Our results suggest that the RTT scale is a valid and reliable instrument for the measurement of test anxiety among Portuguese Medical Students.

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.

25-OH Vitamin D Levels and Cognitive Performance: Longitudinal Assessment in a Healthy Aging Cohort.

Background: Declining serum levels of 25-hydroxyvitamin D [25(OH)D, a biomarker of vitamin D status] with aging is a well-recognized phenomenon. However, scarce information is available on the relation between 25(OH)D levels and cognitive performance over time in older individuals. Our purpose was to evaluate, longitudinally, the association of 25(OH)D with cognitive function in a healthy older adults' cohort. Methods: Sixty-four individuals over 55 years-old with no cognitive impairment, clustered as healthy "Poor" and "Good" cognitive performers, were followed for an average of 18 months. Seasonal-adjusted 25(OH)D serum levels (measured by high-performance liquid chromatography-tandem mass spectrometry) were related, longitudinally, with cognitive (memory and general/executive) composite scores. Results: Overall seasonal-adjusted median serum 25(OH)D level was of 47 nmol/l [interquartile range (IQR), 38-60 nmol/l]. A negative correlation between baseline 25(OH)D and the general/executive composite score was found in the "Poor" cognitive performers (r s = -0.52, p = 0.006), an association lost after adjusting 25(OH)D levels for the season. No effect was found in both groups between seasonal-adjusted 25(OH)D levels and the variation of both memory and general/executive composites during follow-up when adjusted for age, gender and education level. Conclusion: In this healthy older population with no cognitive impairment, lower serum levels of 25(OH)D were not longitudinally associated with poorer cognitive scores.

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.