Early Life Cognition Research Articles

Trajectories of Human Milk Gangliosides during the First Four Hundred Days and Maternal-to-Offspring Transfer of Gangliosides: Results from a Chinese Cohort Study

BackgroundGangliosides are crucial for early-life cognition and immunity development. However, limited data exist on gangliosides within the Chinese population, and maternal-to-fetal/infant ganglioside transport remains unclear. ObjectivesThis study aimed to investigate gangliosides concentrations and trajectories in Chinese human milk during the first 400 d of lactation, and seek to understand gangliosides transmission between mother and offspring. MethodsThis study involved 921 cross-sectional participants providing human milk samples across 0–400 d of lactation and 136 longitudinal participants offering maternal plasma, cord plasma, and human milk samples within the first 45 d postpartum. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used for the quantification of gangliosides. ResultsHuman milk GM3 (Neu5Acα2-3Galβ1-4GlcβCer) concentration increased from 2.29 ± 1.87 to 13.93 ± 4.82 μg/mL, whereas GD3 (Neu5Acα2-8Neu5Acα2-3Galβ1-4GlcβCer) decreased from 17.94 ± 6.41 to 0.30 ± 0.50 μg/mL during the first 400 d postpartum (all P < 0.05). Consistent results were observed in cross-sectional and longitudinal participants. GD3 concentration gradually increased from maternal plasma (1.58 μg/mL) through cord plasma (2.05 μg/mL) to colostrum (21.35 μg/mL). Significant positive correlations were observed between maternal and cord plasma for both GM3 (r = 0.30, P < 0.001) and GD3 (r = 0.35, P < 0.001), and maternal plasma GD3 also correlated positively with colostrum concentrations (r = 0.21, P = 0.015). Additionally, in maternal and cord plasma, gangliosides were mainly linked with 16- and 18-carbon fatty acids. However, human milk GM3 showed a broad spectrum of fatty acid chain lengths, whereas GD3 was primarily tied to very long-chain fatty acids (≥20 carbon). ConclusionsWe identified an increase in GM3 and a decrease in GD3 concentration in human milk, with GD3 notably more concentrated in cord plasma and colostrum. Importantly, ganglioside concentrations in maternal plasma positively correlated with those in cord plasma and colostrum. Our findings contribute to the existing Chinese data on gangliosides and enhance understanding of their transmission patterns from mother to offspring.This trial was registered at chictr.org.cn as ChiCTR1800015387.

EARLY LIFE COGNITION, EDUCATION, AND DEMENTIA RISK

Abstract Educational attainment is one of the strongest predictors of Alzheimer’s and Related Dementias (ADRD). Yet, much remains unknown as to how early life factors, particularly early life cognitive function, and early life environments, such as family environments, help explain why education so robustly protects against later life dementia. Is the influence of educational attainment not so much the additional schooling, but rather antecedent factors, like early life cognition and family environments that both build cognitive reserve and predict subsequent educational attainment? In short, is education merely a proxy for these antecedent influences? Consequently, we use the Wisconsin Longitudinal Study, which includes 80 years of prospectively collected data on a sample of 1 in every 3 high school graduates, and a selected sibling, from the class of 1957. Sibling models, and the inclusion of prospectively collected early life cognitive function and educational histories, allows us to explore the role of these early life conditions and the role they play in shaping the relationship between education and ADRD. We find a robust independent influence of education on ADRD risk, early life family environments had little impact on the relationship. Adolescent cognition, however, which we show is influenced by family environments, does partly explain why educational attainment influences later life ADRD risk, though both adolescent IQ and education independently influence the risk for and resilience against dementia.

Blood pressure change and cognition in childhood and early adulthood: a systematic review.

Introduction:High blood pressure in midlife is an established risk factor for cognitive decline and dementia but less is known about the impact of raised blood pressure on cognition in childhood and early adulthood.Method:We systematically reviewed and quantified the existing evidence base relating to blood pressure in early life and subsequent cognitive performance. Medline, Embase, PsycINFOo, Scopus, and Web of Science were searched from inception to July 2020. We included longitudinal cohort and case–control studies involving participants aged 0–40 years with a baseline and at least one follow-up blood pressure assessment alongside at least one measure of cognition, occurring at the same time as, or subsequent to blood pressure measures. Risk of bias was assessed independently by two reviewers. PROSPERO registration CRD42020214655.Results:Of a total of 5638 records identified, three cohort and two case–control studies were included with ages ranging from 3 to early 30s. Repeated blood pressure measurements averaged over 25 years or cumulative blood pressure in the 25–30 years prior to assessment of cognitive function were associated with poorer cognitive performance in the two largest cohort studies. The smallest cohort study reported no evidence of an association and the results from the two case–control studies were contradictory. All studies were at risk of bias.Conclusion:Overall, the evidence in this area is lacking and study quality is mixed. Our review highlights an urgent need for studies evaluating the potential for a relationship between raised blood pressure and poorer cognition in early life given the potential for possible risk reduction if such a relationship exists.

The Role of Intranasal Oxytocin on Social Cognition: An Integrative Human Lifespan Approach.

This narrative review synthesizes research from the last two decades on the modulatory role of intranasal OT administration (IN-OT) on social cognition in early life, young/middle adulthood, and older adulthood. Advances and knowledge gaps are identified, and future research directions are discussed within an integrative human lifespan framework to guide novel research on IN-OT and social cognition. Current evidence regarding IN-OT modulation of social-cognitive processes, behavior, and related neurocircuitry is mixed, with some studies suggesting benefits (e.g., improved social perception/interactions, emotion processing) depending on contextual (e.g., social stimuli) and interindividual factors (e.g., age, sex, clinical status). Current research, however, is limited by a focus on isolated life phases, males, and select clinical populations as well as a lack of standardized protocols. This literature-based reflection proposes that greater generalizability of findings and scientific advancement on social-cognitive modulation via IN-OT require standardized, multi-method, longitudinal, and cross-sequential assessments in well-powered, well-controlled, and representative samples in line with an integrative lifespan approach, which considers development as a lifelong dynamic process involving both change and stability characterized by the interplay between genetic, neurobiological, and socio-behavioral factors.

Importance of Follow-up Studies to Examine Sustained Effects of Early Nutrition Interventions.

With 43% of children <5 years of age worldwide at risk for poor mental development,1 interventions aimed at sustained improvement of cognition are urgently needed. Nutrition has proven to be an important predictor of neurodevelopment, and interventions to address malnutrition in many low- and middle-income countries have improved children’s short-term development.2 The expectation is that the early life neurobehavioral benefits, when the brain is developing rapidly and is most sensitive to interventions, extend beyond childhood. Yet little is known about the consequences of improving cognition in early life on school-aged and adult outcomes, such as school achievement, economic productivity, and overall well-being. Only a handful of nutrition interventions in children <5 years old follow up with the same participants to examine long-term benefits. Consequently, the follow-up study by Kvestad et al3 titled “Vitamin B12, Folate, and Cognition in 6- to 9-Year-Olds: A Randomized Controlled Trial” makes an important contribution to our understanding of the sustainability of early benefits. One of the longest nutrition intervention follow-up studies is the seminal Institute of … Address correspondence to Beverley-Ann Biggs, PhD, MBBS, FRCP, FRACP, Department of Medicine, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Level 5, 792 Elizabeth St, Building 248, Melbourne, VIC 3010, Australia. E-mail: babiggs{at}unimelb.edu.au

Genetic Burden for Late-Life Neurodegenerative Disease and Its Association With Early-Life Lipids, Brain, Behavior, and Cognition.

BackgroundGenetics play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia. Part of the individual differences in risk for these diseases can be traced back decades before the onset of disease symptoms. Previous studies have shown evidence for plausible links of apolipoprotein E (APOE), the most important genetic marker for Alzheimer’s disease, with early-life cognition and neuroimaging markers. We aimed to assess whether genome-wide genetic burden for the aforementioned neurodegenerative diseases plays a role in early-life processes.MethodsWe studied children from the Generation R Study, a prospective birth cohort. APOE genotypes and polygenic genetic burdens for Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia were obtained through genome-wide genotyping. Non-verbal intelligence was assessed through cognitive tests at the research center around the age of 6 years, and educational attainment through a national school performance test around the age of 11 years. The Child Behavior Checklist was administered around the age of 10 years, and data from the anxious/depressed, withdrawn/depressed, and the internalizing behavior problems scales were used. Children participated in a neuroimaging study when they were 10 years old, in which structural brain metrics were obtained. Lipid serum profiles, which may be influenced by APOE genotype, were assessed from venal blood obtained around the age of 6 years. The sample size per analysis varied between 1,641 and 3,650 children due to completeness of data.ResultsWe did not find evidence that APOE genotype or the polygenic scores impact on childhood nonverbal intelligence, educational attainment, internalizing behavior, and global brain structural measures including total brain volume and whole brain fractional anisotropy (all p > 0.05). Carriership of the APOE ε2 allele was associated with lower and APOE ε4 with higher low-density lipoprotein cholesterol concentrations when compared to APOE ε3/ε3 carriers.ConclusionWe found no evidence that genetic burden for late-life neurodegenerative diseases associates with early-life cognition, internalizing behavior, or global brain structure.

IGFBP2 Plays an Essential Role in Cognitive Development during Early Life.

Identifying the mechanisms underlying cognitive development in early life is a critical objective. The expression of insulin‐like growth factor binding protein 2 (IGFBP2) in the hippocampus increases during neonatal development and is associated with learning and memory, but a causal connection has not been established. Here, it is reported that neurons and astrocytes expressing IGFBP2 are distributed throughout the hippocampus. IGFBP2 enhances excitatory inputs onto CA1 pyramidal neurons, facilitating intrinsic excitability and spike transmission, and regulates plasticity at excitatory synapses in a cell‐type specific manner. It facilitates long‐term potentiation (LTP) by enhancing N‐methyl‐d‐aspartate (NMDA) receptor‐dependent excitatory postsynaptic current (EPSC), and enhances neurite proliferation and elongation. Knockout of igfbp2 reduces the numbers of pyramidal cells and interneurons, impairs LTP and cognitive performance, and reduces tonic excitation of pyramidal neurons that are all rescued by IGFBP2. The results provide insight into the requirement for IGFBP2 in cognition in early life.

The effect of mid-life insulin resistance and type 2 diabetes on older-age cognitive state: the explanatory role of early-life advantage

Aims/hypothesisType 2 diabetes, hyperglycaemia and insulin resistance are associated with cognitive impairment and dementia, but causal inference studies using Mendelian randomisation do not confirm this. We hypothesised that early-life cognition and social/educational advantage may confound the relationship.MethodsFrom the population-based British 1946 birth cohort, a maximum number of 1780 participants had metabolic variables (type 2 diabetes, insulin resistance [HOMA2-IR] and HbA1c) assessed at age 60–64 years, and cognitive state (Addenbrooke’s Cognitive Examination III [ACE-III]) and verbal memory assessed at age 69 years. Earlier-life measures included socioeconomic position (SEP), cognition at age 8 years and educational attainment. Polygenic risk scores (PRSs) for type 2 diabetes were calculated. We first used a PRS approach with multivariable linear regression to estimate associations between PRSs and metabolic traits and later-life cognitive state. Second, using a path model approach, we estimated the interrelationships between earlier-life measures, features of mid-life type 2 diabetes and cognitive state at age 69 years. All models were adjusted for sex.ResultsThe externally weighted PRS for type 2 diabetes was associated with mid-life metabolic traits (e.g. HOMA2-IR β = 0.08 [95% CI 0.02, 0.16]), but not with ACE-III (β = 0.04 [−0.02, 0.90]) or other cognitive outcomes. While there was an association between HOMA2-IR and subsequent ACE-III (β = −0.09 [−0.15, −0.03]), path modelling showed no direct effect (β = −0.01 [−0.06, 0.03]) after accounting for the association between childhood SEP and education with HOMA2-IR. The same pattern was observed for later-life verbal memory.Conclusions/interpretationAssociations between type 2 diabetes and mid-life metabolic traits with subsequent cognitive state do not appear causal, and instead they may be explained by SEP in early life, childhood cognition and educational attainment. Therefore, glucose-lowering medication may be unlikely to combat cognitive impairment in older age.

APOE effects on cognition from childhood to adolescence

The ε4 allele of APOE is a well-established genetic risk factor for cognitive aging and dementia, but its influence on early life cognition is unknown. Consequently, we assessed associations of APOE genotypes with cognitive performance during 7, 12, and 16 year-assessments in our ongoing Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). In general, APOE ε4 was associated with lower Verbal, Performance, and Full Scale IQ scores during childhood and adolescence (e.g., Full Scale IQ was lower by 1.91 points per ε4 allele, d = −0.13), with larger effects in females (e.g., average Full Scale IQ scores were 3.41 points lower in females per each ε4 allele vs. 0.33 points lower in males). Thus, these results suggest that deleterious effects of the APOE ε4 allele are manifested before adulthood, especially in females, and support both early origin theories and differential life-course vulnerabilities for later cognitive impairment.

Socioeconomic Attainment of Extremely Low Birth Weight Survivors: The Role of Early Cognition.

To determine: (1) if childhood cognitive and academic abilities mediate the association between being born at extremely low birth weight (ELBW) and socioeconomic attainment at age 29 to 36 years; (2) which cognitive abilities (IQ, verbal abilities, fluid intelligence, mathematical abilities, or academic achievement) most strongly mediate this association; and (3) if the mediating role of cognition is different in ELBW survivors with significant neurosensory impairment (NSI). A prospective, longitudinal cohort of 100 Canadian ELBW survivors born between 1977 and 1982 and 89 normal birth weight comparison participants were used to examine the mediating role of childhood cognition by using 5 cognitive mediators assessed at age 8 years (overall IQ, verbal IQ, performance IQ, quantitative ability, and academic achievement) on socioeconomic attainment at adulthood. Socioeconomic attainment was defined as personal annual earnings and full-time employment assessed via self-report at age 29 to 36 years. Mediation models revealed that childhood cognition mediated the association between ELBW status and income attainment, with mathematical abilities and overall IQ each accounting for 26% of the direct effect. Mediated effects were not statistically significant in full-time employment models. For both outcomes, the mediating effect of cognition was stronger for ELBW survivors with NSI. Childhood cognitive abilities partially mediate associations between ELBW status and adult income attainment. Early life cognition is a critical predictor of socioeconomic attainment in ELBW survivors, particularly in those born with NSI. Interventions aimed at enhancing early cognition in ELBW survivors may help optimize their later socioeconomic attainment.

Educational Inequalities in Health Behaviors at Midlife: Is There a Role for Early-life Cognition?

Education is a fundamental cause of social inequalities in health because it influences the distribution of resources, including money, knowledge, power, prestige, and beneficial social connections, that can be used in situ to influence health. Recent studies have highlighted early-life cognition as commonly indicating the propensity for educational attainment and determining health and age of mortality. Health behaviors provide a plausible mechanism linking both education and cognition to later-life health and mortality. We examine the role of education and cognition in predicting smoking, heavy drinking, and physical inactivity at midlife using data from the Wisconsin Longitudinal Study (N = 10,317), National Survey of Health and Development (N = 5,362), and National Childhood Development Study (N = 16,782). Adolescent cognition was associated with education but was inconsistently associated with health behaviors. Education, however, was robustly associated with improved health behaviors after adjusting for cognition. Analyses highlight structural inequalities over individual capabilities when studying health behaviors.

Can we understand why cognitive function predicts mortality? Results from the Caerphilly Prospective Study (CaPS)

The association between cognitive function and mortality is of increasing interest. We followed 1870 men aged 55–69 years at cognitive assessment for 16 years to establish associations with all case and cause specific mortality. Cognitive assessment included AH4, 4 choice reaction time (used as estimates of mid-life cognition) and the National Adult Reading Test (used as an estimate of early-life cognition). Causal models were tested for the effects of a) early-life cognition, b) confounding through mid-life disease, and c) the effects of sociodemographic and lifestyle factors. A fully adjusted model was also tested. Age adjusted associations with mid-life cognitive function were found with mortality from circulatory, coronary, respiratory and digestive disease but not from cancer mortality. Age adjusted associations were attenuated and in some cases nullified by further adjustment for each of early-life cognition, mid-life disease risk and sociodemographic and lifestyle factors. These associations cannot be assumed to be unbiased estimates of effect due to the complex confounding structures that exist in these data. Future studies should explore natural experiments, use different populations where the confounding structures may be different and evaluate more complex methods that may be able to deal with the inherent complexities of a life course perspective.

PL-04-01: Early life cognition and experience and late-life dementia

PL-04-01: Early life cognition and experience and late-life dementia

Childhood and current cognitive function in healthy 80-year-olds: a DT-MRI study.

Diffusion tensor MR imaging (DT-MRI) yields information on early pathological changes in white matter of the ageing brain which may correlate with cognitive function. However, because individuals vary in their cognitive ability, a measurement of prior cognition from youth is required to understand fully the significance of MR imaging changes associated with ageing. Here, diffusion tensor parameters and cognitive function were measured in a cohort of 30 older subjects whose cognitive ability was measured at age 11 and 80. There was a significant correlation between diffusion anisotropy measured in the centrum semiovale at age 80 and mental ability determined at age 11 and 80. These novel results suggest, that MR imaging studies of white matter structure and its relationship to mental ability in ageing should control for early life cognition.

Grounded in the World: Developmental Origins of the Embodied Mind.

Piaget's (1952) question of how the adult mind emerges from the sensorimotor infant is still the framing issue for developmental psychology. Here I suggest that real-life skill is better understood if the sensorimotor origins of cognition are not abandoned. Skilled people are not only better at both abstract and logical thinking but also at processing the world "online" and, most important, seamlessly and rapidly shifting between the two modes. I illustrate the tight coupling between action, perception, and cognition in early life and propose that this coupling remains but becomes more flexibly adaptive. Further, I show that the language of dynamics is appropriate to capture these mind-body-world interconnections.