Increases in regional brain volume across two native South American male populations.

Industrialized environments, despite benefits such as higher levels of formal education and lower rates of infections, can also have pernicious impacts upon brain atrophy. Partly for this reason, comparing age-related brain volume trajectories between industrialized and non-industrialized populations can help to suggest lifestyle correlates of brain health. The Tsimane, indigenous to the Bolivian Amazon, derive their subsistence from foraging and horticulture and are physically active. The Moseten, a mixed-ethnicity farming population, are physically active but less than the Tsimane. Within both populations (N = 1024; age range = 46-83), we calculated regional brain volumes from computed tomography and compared their cross-sectional trends with age to those of UK Biobank (UKBB) participants (N = 19,973; same age range). Surprisingly among Tsimane and Moseten (T/M) males, some parietal and occipital structures mediating visuospatial abilities exhibit small but significant increases in regional volume with age. UKBB males exhibit a steeper negative trend of regional volume with age in frontal and temporal structures compared to T/M males. However, T/M females exhibit significantly steeper rates of brain volume decrease with age compared to UKBB females, particularly for some cerebro-cortical structures (e.g., left subparietal cortex). Across the three populations, observed trends exhibit no interhemispheric asymmetry. In conclusion, the age-related rate of regional brain volume change may differ by lifestyle and sex. The lack of brain volume reduction with age is not known to exist in other human population, highlighting the putative role of lifestyle in constraining regional brain atrophy and promoting elements of non-industrialized lifestyle like higher physical activity.

Poor Oral Health Is Associated With Inflammation, Aortic Valve Calcification, and Brain Volume Among Forager-Farmers.

Poor oral health is associated with cardiovascular disease and dementia. Potential pathways include sepsis from oral bacteria, systemic inflammation, and nutritional deficiencies. However, in post-industrialized populations, links between oral health and chronic disease may be confounded because the lower socioeconomic exposome (poor diet, pollution, and low physical activity) often entails insufficient dental care. We assessed tooth loss, caries, and damaged teeth, in relation to cardiovascular and brain aging among the Tsimane, a subsistence population living a relatively traditional forager-horticulturalist lifestyle with poor dental health, but minimal cardiovascular disease and dementia. Dental health was assessed by a physician in 739 participants aged 40-92 years with cardiac and brain health measured by chest computed tomography (CT; n = 728) and brain CT (n = 605). A subset of 356 individuals aged 60+ were also assessed for dementia and mild cognitive impairment (n = 33 impaired). Tooth loss was highly prevalent, with 2.2 teeth lost per decade and a 2-fold greater loss in women. The number of teeth with exposed pulp was associated with higher inflammation, as measured by cytokine levels and white blood cell counts, and lower body mass index. Coronary artery calcium and thoracic aortic calcium were not associated with tooth loss or damaged teeth. However, aortic valve calcification and brain tissue loss were higher in those who had more teeth with exposed pulp. Overall, these results suggest that dental health is associated with indicators of chronic diseases in the absence of typical confounds, even in a population with low cardiovascular and dementia risk factors.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

Background: In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. Methodology: In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). Results: Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007). Conclusions and Implications: Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.

Adolescence is characterized by more sedentary behaviour and less physical activity even among highly active forager-farmers.

Over 80% of adolescents worldwide are insufficiently active, posing massive public health and economic challenges. Declining physical activity (PA) and sex differences in PA consistently accompany transitions from childhood to adulthood in post-industrialized populations and are attributed to psychosocial and environmental factors. An overarching evolutionary theoretical framework and data from pre-industrialized populations are lacking. This cross-sectional study tests hypotheses from life history theory, that adolescent PA is inversely related to age, but this association is mediated by Tanner stage, reflecting higher and sex-specific energetic demands for growth and reproductive maturation. Detailed measures of PA and pubertal maturation are assessed among Tsimane forager-farmers (age: 7-22 years; 50% female, n = 110). Most Tsimane sampled (71%) meet World Health Organization PA guidelines (greater than or equal to 60 min/day of moderate-to-vigorous PA). Like post-industrialized populations, sex differences and inverse age-activity associations were observed. Tanner stage significantly mediated age-activity associations. Adolescence presents difficulties to PA engagement that warrant further consideration in PA intervention approaches to improve public health.

Metapopulation dynamics of SARS-CoV-2 transmission in a small-scale Amazonian society.

The severity of infectious disease outbreaks is governed by patterns of human contact, which vary by geography, social organization, mobility, access to technology and healthcare, economic development, and culture. Whereas globalized societies and urban centers exhibit characteristics that can heighten vulnerability to pandemics, small-scale subsistence societies occupying remote, rural areas may be buffered. Accordingly, voluntary collective isolation has been proposed as one strategy to mitigate the impacts of COVID-19 and other pandemics on small-scale Indigenous populations with minimal access to healthcare infrastructure. To assess the vulnerability of such populations and the viability of interventions such as voluntary collective isolation, we simulate and analyze the dynamics of SARS-CoV-2 infection among Amazonian forager-horticulturalists in Bolivia using a stochastic network metapopulation model parameterized with high-resolution empirical data on population structure, mobility, and contact networks. Our model suggests that relative isolation offers little protection at the population level (expected approximately 80% cumulative incidence), and more remote communities are not conferred protection via greater distance from outside sources of infection, due to common features of small-scale societies that promote rapid disease transmission such as high rates of travel and dense social networks. Neighborhood density, central household location in villages, and household size greatly increase the individual risk of infection. Simulated interventions further demonstrate that without implausibly high levels of centralized control, collective isolation is unlikely to be effective, especially if it is difficult to restrict visitation between communities as well as travel to outside areas. Finally, comparison of model results to empirical COVID-19 outcomes measured via seroassay suggest that our theoretical model is successful at predicting outbreak severity at both the population and community levels. Taken together, these findings suggest that the social organization and relative isolation from urban centers of many rural Indigenous communities offer little protection from pandemics and that standard control measures, including vaccination, are required to counteract effects of tight-knit social structures characteristic of small-scale populations.

Apolipoprotein-ε4 is associated with higher fecundity in a natural fertility population.

In many populations, the apolipoprotein-ε4 (APOE-ε4) allele increases the risk for several chronic diseases of aging, including dementia and cardiovascular disease; despite these harmful effects at later ages, the APOE-ε4 allele remains prevalent. We assess the impact of APOE-ε4 on fertility and its proximate determinants (age at first reproduction, interbirth interval) among the Tsimane, a natural fertility population of forager-horticulturalists. Among 795 women aged 13 to 90 (20% APOE-ε4 carriers), those with at least one APOE-ε4 allele had 0.3 to 0.5 more children than (ε3/ε3) homozygotes, while those with two APOE-ε4 alleles gave birth to 1.4 to 2.1 more children. APOE-ε4 carriers achieve higher fertility by beginning reproduction 0.8 years earlier and having a 0.23-year shorter interbirth interval. Our findings add to a growing body of literature suggesting a need for studies of populations living in ancestrally relevant environments to assess how alleles that are deleterious in sedentary urban environments may have been maintained by selection throughout human evolutionary history.

Energetic costs of testosterone in two subsistence populations.

OBJECTIVE: Testosterone plays a role in mediating energetic trade-offs between growth, maintenance, and reproduction. Investments in a high testosterone phenotype trade-off against other functions, particularly survival-enhancing immune function and cellular repair; thus only individuals in good condition can maintain both a high testosterone phenotype and somatic maintenance. While these effects are observed in experimental manipulations, they are difficult to demonstrate in free-living animals, particularly in humans. We hypothesize that individuals with higher testosterone will have higher energetic expenditures than those with lower testosterone. METHODS: Total energetic expenditure (TEE) was quantified using doubly labeled water in n = 40 Tsimane forager-horticulturalists (50% male, 18-87 years) and n = 11 Hadza hunter-gatherers (100% male, 18-65 years), two populations living subsistence lifestyles, high levels of physical activity, and high infectious burden. Urinary testosterone, TEE, body composition, and physical activity were measured to assess potential physical and behavioral costs associated with a high testosterone phenotype. RESULTS: Endogenous male testosterone was significantly associated with energetic expenditure, controlling for fat free mass; a one standard deviation increase in testosterone is associated with the expenditure of an additional 96-240 calories per day. DISCUSSION: These results suggest that a high testosterone phenotype, while beneficial for male reproduction, is also energetically expensive and likely only possible to maintain in healthy males in robust condition.

Adolescence is characterized by more sedentary behavior and less physical activity even among highly active forager-farmers.

Over 80% of adolescents worldwide are insufficiently active, posing massive public health and economic challenges. Declining physical activity (PA) and sex differences in PA consistently accompany transitions from childhood to adulthood in post-industrialized populations and are attributed to psychosocial and environmental factors. An overarching evolutionary theoretical framework and data from pre-industrialized populations are lacking. In this cross-sectional study we test a hypothesis from life history theory, that adolescent PA reductions reflect an evolved strategy to conserve energy, given the increasing sex-specific energetic demands for growth and reproductive maturation. Detailed measures of PA and pubertal maturation are assessed among Tsimane forager-farmers (age: 7-22 yrs.; 50% female, n=110). We find that 71% of Tsimane sampled meet World Health Organization PA guidelines (≥60 minutes/day of moderate-to-vigorous PA). Consistent with post-industrialized populations, we observe sex differences and inverse age-activity associations mediated by Tanner stage. Physical inactivity in adolescence is distinct from other health risk behaviors and also not merely resulting from obesogenic environments.

Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.

Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.

Female cooperative labour networks in hunter-gatherers and horticulturalists.

Cooperation in food acquisition is a hallmark of the human species. Given that costs and benefits of cooperation vary among production regimes and work activities, the transition from hunting-and-gathering to agriculture is likely to have reshaped the structure of cooperative subsistence networks. Hunter-gatherers often forage in groups and are generally more interdependent and experience higher short-term food acquisition risk than horticulturalists, suggesting that cooperative labour should be more widespread and frequent for hunter-gatherers. Here we compare female cooperative labour networks of Batek hunter-gatherers of Peninsular Malaysia and Tsimane forager-horticulturalists of Bolivia. We find that Batek foraging results in high daily variation in labour partnerships, facilitating frequent cooperation in diffuse networks comprised of kin and non-kin. By contrast, Tsimane horticulture involves more restricted giving and receiving of labour, confined mostly to spouses and primary or distant kin. Tsimane women also interact with few individuals in the context of hunting/fishing activities and forage mainly with spouses and primary kin. These differences give rise to camp- or village-level networks that are more modular (have more substructure when partitioned) among Tsimane horticulturalists. Our findings suggest that subsistence activities shape the formation and extent of female social networks, particularly with respect to connections with other women and non-kin. We discuss the implications of restricted female labour networks in the context of gender relations, power dynamics and the adoption of farming in humans. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.

Prevalence of dementia and mild cognitive impairment in indigenous Bolivian forager-horticulturalists.

INTRODUCTION: We evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle. METHODS: Participants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans. RESULTS: Tsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia. DISCUSSION: The prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

Helminth infection is associated with dampened cytokine responses to viral and bacterial stimulations in Tsimane forager-horticulturalists.

BACKGROUND: Soil-transmitted helminths (STHs) and humans share long co-evolutionary histories over which STHs have evolved strategies to permit their persistence by downregulating host immunity. Understanding the interactions between STHs and other pathogens can inform our understanding of human evolution and contemporary disease patterns. METHODOLOGY: We worked with Tsimane forager-horticulturalists in the Bolivian Amazon, where STHs are prevalent. We tested whether STHs and eosinophil levels-likely indicative of infection in this population-are associated with dampened immune responses to in vitro stimulation with H1N1 and lipopolysaccharide (LPS) antigens. Whole blood samples (n = 179) were treated with H1N1 vaccine and LPS and assayed for 13 cytokines (INF-γ, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, GM-CSF and TNF-ɑ). We evaluated how STHs and eosinophil levels affected cytokine responses and T helper (Th) 1 and Th2-cytokine suite responses to stimulation. RESULTS: Infection with Ascaris lumbricoides was significantly (P ≤ 0.05) associated with lower response of some cytokines to H1N1 and LPS in women. Eosinophils were significantly negatively associated with some cytokine responses to H1N1 and LPS, with the strongest effects in women, and associated with a reduced Th1- and Th2-cytokine response to H1N1 and LPS in women and men. CONCLUSIONS AND IMPLICATIONS: Consistent with the 'old friends' and hygiene hypotheses, we find that STHs were associated with dampened cytokine responses to certain viral and bacterial antigens. This suggests that STH infections may play an essential role in immune response regulation and that the lack of STH immune priming in industrialized populations may increase the risk of over-reactive immunity. Lay Summary: Indicators of helminth infection were associated with dampened cytokine immune responses to in vitro stimulation with viral and bacterial antigens in Tsimane forager-horticulturalists in the Bolivian Amazon, consistent with the 'old friends' and hygiene hypotheses.

The Indigenous South American Tsimane Exhibit Relatively Modest Decrease in Brain Volume With Age Despite High Systemic Inflammation.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40-94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate ß^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. ß^T was compared to the corresponding regression coefficient estimate ß^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis ß T = ß R was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.

High prevalence of sternal foramina in indigenous Bolivians compared to Midwest Americans and indigenous North Americans (sternal foramina in indigenous Bolivians).

The sternal foramen, usually an asymptomatic osteological defect, can lead to catastrophic consequences if not recognized prior to certain medical procedures. This study reports the prevalence of a sternal foramen in two South Amerindian populations compared with other published populations. We evaluated the presence of sternal foramina using thoracic computed tomography scans of 1334 (48% female) participants from two indigenous populations of Bolivia (n = 900 Tsimane, 434 Moseten). The prevalence of sternal foramina was compared to two U.S. populations of similar sex/age distribution (n = 572 Midwest Americans, 131 self-identified Native North Americans) via similar CT scans. A sternal foramen was significantly more common in the two Bolivian populations (prevalence ranging from 12.8 to 13.4%), compared to 4.4-5.1% in the two U.S. groups, consistent with prior estimates in studies from industrialized populations. Males had higher frequency of a sternal foramen compared to females in each of the four groups (OR = 1.904, 95% CI: 1.418-2.568, p < 0.001). Age was not associated with sternal foramen presence. These data show both a higher rate of sternal foramina in the South Amerindian populations versus comparator populations in North America and the highest rate of any studied living population. Although it is not possible to determine from our data the relative contribution of genetics versus early life or environmental causes to the higher rates of sternal foramen, we note that small prior studies have likewise demonstrated a higher prevalence in lower income countries. Further determination of the contributing factors warrants greater investigation and research.

Relationship of sanitation, water boiling, and mosquito nets to health biomarkers in a rural subsistence population.

OBJECTIVES: Throughout human evolutionary history, parasites and pathogens were a major cause of mortality-modern urban life with public health infrastructure has changed disease exposure. We examine associations between boiling water, using latrines, mosquito net usage, and biomarkers among the Tsimane, a nonindustrial subsistence population with little public health infrastructure. METHODS: We conducted cross sectional surveys on water, latrines, and bed nets among 507 heads of households (aged 18-92 years, median age 41 years). Regression models estimated associations between behaviors and health biomarkers (ie, white blood cell count [WBC], hemoglobin, eosinophil count, and erythrocyte sedimentation rate) adjusting for age, sex, body mass index, wealth, schooling, and distance to the nearby market town. RESULTS: Latrine use is associated with 6.5% lower WBC count (ß = -679.6, P = .031, SE = 314.1), 17.4% lower eosinophil counts (ß = -244.7, P = .023, SE = 107.2), and reduced odds of eosinophilia (adjusted OR = 0.40, P < .019, 95% CI = 0.18-0.86). Boiling water and mosquito net use are not significantly associated with any biomarkers measured. CONCLUSIONS: In a subsistence population currently undergoing epidemiological transition, we find that latrine use was associated with several objective measures of health. This suggests that relatively low cost and low maintenance public health interventions may wish to focus on latrine use, as there is unmet need and potential health benefits for those who use latrines. Additionally, while the cost is higher, public health organizations aimed at improving sanitation may be able to use minimally invasive field-collected biomarkers as a diagnostic to objectively test the efficacy of interventions with greater specificity than anthropometric measurements.

Age-independent increases in male salivary testosterone during horticultural activity among Tsimane forager-farmers.

Testosterone plays an important role in mediating male reproductive trade-offs in many vertebrate species, augmenting muscle and influencing behavior necessary for male-male competition and mating-effort. Among humans, testosterone may also play a key role in facilitating male provisioning of offspring as muscular and neuromuscular performance are deeply influenced by acute changes in testosterone. This study examines acute changes in salivary testosterone among 63 Tsimane men ranging in age from 16-80 (mean 38.2) years during one-hour bouts of tree-chopping while clearing horticultural plots. The Tsimane forager-horticulturalists living in the Bolivian Amazon experience high energy expenditure associated with food production, have high levels of parasites and pathogens, and display significantly lower baseline salivary testosterone than age-matched US males. Mixed-effects models controlling for BMI and time of specimen collection reveal increased salivary testosterone (p<0.001) equivalent to a 48.6% rise, after one hour of tree chopping. Age had no effect on baseline (p=0.656) or change in testosterone (p=0.530); self-reported illness did not modify testosterone change (p=0.488). A comparison of these results to the relative change in testosterone during a competitive soccer tournament in the same population reveals larger relative changes in testosterone following resource production (tree chopping), compared to competition (soccer). These findings highlight the importance of moving beyond a unidimensional focus on changes in testosterone and male-male aggression to investigate the importance of testosterone-behavior interactions across additional male fitness-related activities. Acutely increased testosterone during muscularly intensive horticultural food production may facilitate male productivity and provisioning.