Social epidemiology

Social epidemiology is the branch of epidemiology concerned with understanding how social and economic characteristics influence states of health in populations. There has been a resurgence recently in interest among epidemiologists about the roles that social and economic factors play in determining health, leading to valuable synergies with the social sciences. The determinants of health commonly studied in social epidemiology include absolute poverty, income inequality, as well as race and discrimination. Recently, social epidemiologists have been at the forefront of conceptual developments within the discipline that view the determinants of health at different levels of social organization. © 2008 Copyright © 2008 Elsevier Inc. All rights reserved

Precis of neuroconstructivism: how the brain constructs cognition

Neuroconstructivism: How the Brain Constructs Cognition proposes a unifying framework for the study of cognitive development that brings together (1) constructivism (which views development as the progressive elaboration of increasingly complex structures), (2) cognitive neuroscience (which aims to understand the neural mechanisms underlying behavior), and (3) computational modeling (which proposes formal and explicit specifications of information processing). The guiding principle of our approach is context dependence, within and (in contrast to Marr [1982]) between levels of organization. We propose that three mechanisms guide the emergence of representations: competition, cooperation, and chronotopy; which themselves allow for two central processes: proactivity and progressive specialization. We suggest that the main outcome of development is partial representations, distributed across distinct functional circuits. This framework is derived by examining development at the level of single neurons, brain systems, and whole organisms. We use the terms encellment, embrainment, and embodiment to describe the higher-level contextual influences that act at each of these levels of organization. To illustrate these mechanisms in operation we provide case studies in early visual perception, infant habituation, phonological development, and object representations in infancy. Three further case studies are concerned with interactions between levels of explanation: social development, atypical development and within that, developmental dyslexia. We conclude that cognitive development arises from a dynamic, contextual change in embodied neural structures leading to partial representations across multiple brain regions and timescales, in response to proactively specified physical and social environment

The lipidome fingerprint of longevity

Lipids were determinants in the appearance and evolution of life. Recent studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species—humans included—demonstrate that both the cell membrane fatty acid profile and lipidome are a species-specific optimized evolutionary adaptation and traits associated with longevity. All these emerging observations point to lipids as a key target to study the molecular mechanisms underlying differences in longevity and suggest the existence of a lipidome profile of long life.Research by the authors was supported by the Spanish Ministry of Science, Innovation, and Universities (Ministerio de Ciencia, Innovación y Universidades, RTI2018-099200-BI00), and the Generalitat of Catalonia: Agency for Management of University and Research Grants (2017SGR696) and Department of Health (SLT002/16/00250) to RP. This study was co-financed by FEDER funds from the European Union (“A way to build Europe”). IRBLleida is a CERCA Programme/Generalitat of Catalonia

Social Networks, Social Relationships, and Their Effects on the Aging Mind and Brain

Key Points • Increasing evidence shows the behavioral, perceptual, and biological pathways by which social relationships and social networks positively impact health outcomes, including those for the aging mind and brain. •The facilitation of healthy aging, in turn, has been shown to increase social participation among older adults through community-based interventions and contributes to societal well-being

The role of the gut and the gastrointestinal microbiome in Parkinson’s disease

INTRODUCTION: Parkinson’s disease (PD) is a disabling and progressive neurodegenerative disorder that is increasing in prevalence with the aging and urbanisation of the global population. The mechanisms underlying PD pathogenesis and progression are incompletely understood. Improved clinical recognition of early and prodromal non-motor symptoms (NMS), namely gastrointestinal (GI) dysfunction, has focused research over the last two decades on the roles of the gut. More recently, the influences of the microbiota-gut-brain-axis (MGBA) in the development and progression of PD have become an intensive area of research. Studies have demonstrated an association between the GM and a variety of PD-related characteristics, identifying important impacts on levodopa metabolism by certain microbiota. Importantly, the effect of device-assisted therapies (DATs) on the GM and the robustness of microbiota compositional differences between PD patients and household controls (HCs) has not been well defined. The aims of this thesis were to 1) investigate GI dysfunction and nutritional patterns in PD, 2) determine if the GM is a biomarker of PD, and 3) investigate the temporal stability of the GM in PD patients receiving standard therapies and those initiating DATs. METHODS: 103 PD patients and 81 HCs were recruited and participants with PD were considered in two sub-cohorts; 1) PD patients initiating DAT; either Deep Brain Stimulation (DBS) (n=10), or levodopa-carbidopa intestinal gel (LCIG) (n=11), who had GM sampling from stool at -2, 0, 2 and 4 weeks around initiation of DAT and baseline, 6 and 12 months following DAT initiation, 2) 82 PD patients receiving standard PD therapies, who had GM sampling from stool at baseline, 6 and 12 months. Validated PD questionnaire metadata ascertaining motor characteristics and NMS, as well as nutritional data in the form of a Food Frequency Questionnaire, were collected for all participants at baseline, 6 and 12 months. Total DNA was isolated from stool before sequencing the V3-V4 region of 16S rRNA. Relative bacterial abundances, diversity measures, compositional differences and clinical-microbiome associations were determined, as well as developing predictive modelling to identify PD patients and assess disease progression. RESULTS: PD patients reported more prevalent and severe GI dysfunction, especially constipation, which was almost three-times more common compared to HC subjects, (78.6% vs 28.4%, p<0.001). PD patients had a higher intake of total carbohydrates (279 g/day vs 232 g/day; p=0.034), which was largely attributable to an increased daily sugar intake (153 g/day vs 119 g/day; p=0.003), particularly of free sugars (61 g/day vs 41 g/day; p=0.001). Significant GM compositional differences across several taxonomic levels were apparent between PD patients and HCs and associated with a number of PD motor and NMS features, as well as certain therapies. Predictive models to distinguish PD from HCs were developed considering global GM profiles, achieving an area under the curve (AUC) of 0.71, which was improved by addition of data on carbohydrate intake (AUC 0.74). Longitudinal analysis demonstrated persistent underrepresentation of known short-chain fatty acid producing bacteria in PD patients, particularly those concerned with butyrate production; Butyricicoccus, Fusicatenibacter, Lachnospiraceae ND3007 group and Erysipelotrichaceae UCG−003. Taxa differences observed over the short-term (four week) sampling period around DAT (DBS and LCIG) initiation, were not sustained at 6 and 12 months. Despite this, persistent longer-term overrepresentation of Prevotella was observed after DBS initiation, and a trend was found that was suggestive of overrepresentation of Roseburia after LCIG initiation. These results suggest that there may be variable shorter and longer-term DBS and LCIG influences on the GM, which are complex and multifactorial. PD progression analysis did not identify distinct persisting GM compositional differences between faster and slower progressing patients, although predictive modelling was strengthened by the consideration of nutritional data, specifically protein intake, and improved the predictive capacity for PD progression. CONCLUSION: This thesis demonstrates that there are numerous clinically significant associations between the gut, GM and PD. GI dysfunction is common, and carbohydrate nutritional intake appears to be different from the general population in PD. Persistent alterations of GM composition in PD compared to HCs were found. These findings provide support for the existence of disturbances of gut homeostatic pathways, which may disrupt intestinal barrier permeability and lead to gut leakiness, in the pathogenesis of PD. This thesis also highlights the potential to use the GM in the identification of PD and the characterisation of disease progression

What does semantic tiling of the cortex tell us about semantics?

Recent use of voxel-wise modeling in cognitive neuroscience suggests that semantic maps tile the cortex. Although this impressive research establishes distributed cortical areas active during the conceptual processing that underlies semantics, it tells us little about the nature of this processing. While mapping concepts between Marr's computational and implementation levels to support neural encoding and decoding, this approach ignores Marr's algorithmic level, central for understanding the mechanisms that implement cognition, in general, and conceptual processing, in particular. Following decades of research in cognitive science and neuroscience, what do we know so far about the representation and processing mechanisms that implement conceptual abilities? Most basically, much is known about the mechanisms associated with: (1) features and frame representations, (2) grounded, abstract, and linguistic representations, (3) knowledge-based inference, (4) concept composition, and (5) conceptual flexibility. Rather than explaining these fundamental representation and processing mechanisms, semantic tiles simply provide a trace of their activity over a relatively short time period within a specific learning context. Establishing the mechanisms that implement conceptual processing in the brain will require more than mapping it to cortical (and sub-cortical) activity, with process models from cognitive science likely to play central roles in specifying the intervening mechanisms. More generally, neuroscience will not achieve its basic goals until it establishes algorithmic-level mechanisms that contribute essential explanations to how the brain works, going beyond simply establishing the brain areas that respond to various task conditions

The impact of macronutritional composition and ketosis on cognitive health : from normal aging to Alzheimer’s disease

Ketogenic diets (KD) are increasingly investigated for the prevention of cognitive decline and Alzheimer’s disease (AD). Without explicitly investigating a KD, this thesis disentangles two of its hallmarks: a reduced dietary carbohydrate/fat-ratio (CFr) and the metabolic state ketosis. Whether health effects from KD are primarily driven by ketosis or from other pathways related macronutritional changes, is not fully understood. Beyond CFr, KD may optionally be modified regarding protein, fat-subtypes, plant/animal-based food proportions, the timing of nutrient intake, and ketogenic supplements. Strategies to induce ketosis in the absence of a carbohydrate restricted diet (Study I) and subsequent associations between induced ketosis and a biomarker essential for brain function (Study II) was investigated in a randomized clinical trial planned and performed within this doctoral project: In a 6-arm cross-over design, 15 healthy older adults (age 65-73, following their usual diet) were exposed to intake of oils with various composition of medium-chain triglycerides (MCT), with and without glucose. Blood levels of ketones (β-hydroxybutyrate, BHB) and brain-derived neurotrophic factor (BDNF) were thereafter monitored for 4 hours. Mature BDNF (mBDNF) and its precursor proBDNF are essential for brain plasticity, and their concentrations in serum have been associated with cognitive health. A methods comparison for measuring blood ketones (Study III) supports the internal validity of Study I and II. The impact of self-reported CFr—in the non-ketogenic range—on cognitive performance (Study IV/V) was investigated by panel analyses on data (year 0, 1, and 2) from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). The sample (n=1259, age 60–77, 47% females) had no substantial cognitive impairment but had risk factors for developing dementia, and cognition at mean level or slightly lower than expected in screening test. Study V added stratified analyses based on genetics (APOE) and insulin status. Study I: A 16-hour non-carbohydrate window and intake of 20 g caprylic acid (C8) contributed roughly equally to induce transient ketosis (0.45 mmol/L, AUC/time venous BHB hour 0-4, when combining the strategies). Coconut oil (which has a ≈7% fraction constituted by C8 and is dominated by lauric acid) did not share the ketogenic properties of purified C8 (difference –0.22 mmol/L, p<0.001). Study II: Contrary to our expectations, change in mBDNF was lower (z-score: β=–0.88, p<0.001) after intake of C8 (higher ketosis) compared to sunflower oil (lower ketosis). Since associations between BHB and mBDNF appeared unrelated (p=0.43) on the individual level, alternative explanations to ketosis as a driver were discussed. In contrast, proBDNF increased more ( β=0.25, p=0.007) after intake of C8 compared to sunflower oil, and individual associations between BHB and proBDNF ( β=0.40, p=0.006) supported ketosis as a mechanistic link. Study III: A handheld ketone meter correlated well with the laboratory method (r=0.91) and agreement was high when applied to venous whole blood (which was our primary outcome). However, absolute values were systematically higher in capillary blood, which should be considered in comparisons between studies. Study IV: A lower CFr (log, z-score) estimated a higher composite z-score on a Neuropsychological Test Battery ( β=–0.022, p=0.011) in linear mixed regression. Methodological advantages of analyzing intake of carbohydrates and fat as a ratio compared to single variables were discussed. No significant associations were found for protein, and the saturated/total fat ratio had non-linear associations with cognitive performance. Study V: APOE (-2/3/4), which is the most important AD risk gene, modified estimates between diet parameters (CFr, protein, saturated/total fat ratio, fiber, composite score) and cognitive performance in a sub-sample with insulin data, excluding diabetics (n=676). By increasing values of a continuous APOE-gradient [–1 (-23), –0.5 (-24), 0 (-33), 1 (-34), 2 (-44)], a less favorable estimate (p<0.0001 for interaction) was found for a Higher-carbohydrates-fiber-Lower-fat-protein composite score. Estimates for -33 were relatively close to zero whereas -44 (with some ambiguity for females) typically had an antagonistic estimate to -23. Relative hypo- and hyper-insulinemia significantly magnified several estimates diet ->cognition in a dose dependent manner, primarily among -34/44. The plant/animal-based proportion of macronutrients was discussed as a potential unmeasured confounder. Conclusions: Macronutritional changes may be an alternative explanation to ketosis for what may drive potential cognitive effects from KD. Time-restricted carbohydrate intake may be considered as an alternative, or a complement, to C8-enriched MCT-oils for achieving mild ketosis. Signaling functions of ketones may be at work in transient mild/moderate ketosis, but whether our BDNF results have any cognitive implications requires further studies. To guide further research, our diet ->cognition analyses have strengthened the case for: (1) a precision nutrition approach based on APOE-genotype and insulin status; (2) not limiting interventions on carbohydrate restriction to the ketogenic range of CFr; (3) considering both ends of the insulin spectrum as representing distinct at-risk types susceptible to diet modifications. APOE-34/44 carriers may be optimal targets for studying potential benefits on brain health from CFr-reduction, and higher protein intake. The concept of universal macronutrient targets may be questioned, and stratified analyses may be encouraged in further studies