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.

Diabetes, Atherosclerosis, and Stenosis by AI.

OBJECTIVE: This study evaluates the relationship between atherosclerotic plaque characteristics (APCs) and angiographic stenosis severity in patients with and without diabetes. Whether APCs differ based on lesion severity and diabetes status is unknown. RESEARCH DESIGN AND METHODS: We retrospectively evaluated 303 subjects from the Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia (CREDENCE) trial referred for invasive coronary angiography with coronary computed tomographic angiography (CCTA) and classified lesions as obstructive (≥50% stenosed) or nonobstructive using blinded core laboratory analysis of quantitative coronary angiography. CCTA quantified APCs, including plaque volume (PV), calcified plaque (CP), noncalcified plaque (NCP), low-density NCP (LD-NCP), lesion length, positive remodeling (PR), high-risk plaque (HRP), and percentage of atheroma volume (PAV; PV normalized for vessel volume). The relationship between APCs, stenosis severity, and diabetes status was assessed. RESULTS: Among the 303 patients, 95 (31.4%) had diabetes. There were 117 lesions in the cohort with diabetes, 58.1% of which were obstructive. Patients with diabetes had greater plaque burden (P = 0.004). Patients with diabetes and nonobstructive disease had greater PV (P = 0.02), PAV (P = 0.02), NCP (P = 0.03), PAV NCP (P = 0.02), diseased vessels (P = 0.03), and maximum stenosis (P = 0.02) than patients without diabetes with nonobstructive disease. APCs were similar between patients with diabetes with nonobstructive disease and patients without diabetes with obstructive disease. Diabetes status did not affect HRP or PR. Patients with diabetes had similar APCs in obstructive and nonobstructive lesions. CONCLUSIONS: Patients with diabetes and nonobstructive stenosis had an association to similar APCs as patients without diabetes who had obstructive stenosis. Among patients with nonobstructive disease, patients with diabetes had more total PV and NCP.

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.

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.

Very Low Prevalence and Incidence of Atrial Fibrillation among Bolivian Forager-Farmers.

Background: Atrial fibrillation is the most common arrhythmia in post-industrialized populations. Older age, hypertension, obesity, chronic inflammation, and diabetes are significant atrial fibrillation risk factors, suggesting that modern urban environments may promote atrial fibrillation. Objective: Here we assess atrial fibrillation prevalence and incidence among tropical horticulturalists of the Bolivian Amazon with high levels of physical activity, a lean diet, and minimal coronary atherosclerosis, but also high infectious disease burden and associated inflammation. Methods: Between 2005-2019, 1314 Tsimane aged 40-94 years (52% female) and 534 Moseten Amerindians aged 40-89 years (50% female) underwent resting 12-lead electrocardiograms to assess atrial fibrillation prevalence. For atrial fibrillation incidence assessment, 1059 (81% of original sample) Tsimane and 310 Moseten (58%) underwent additional ECGs (mean time to follow up 7.0, 1.8 years, respectively). Findings: Only one (male) of 1314 Tsimane (0.076%) and one (male) of 534 Moseten (0.187%) demonstrated atrial fibrillation at baseline. There was one new (female) Tsimane case in 7395 risk years for the 1059 participants with >1 ECG (incidence rate = 0.14 per 1,000 risk years). No new cases were detected among Moseten, based on 542 risk years. Conclusion: Tsimane and Moseten show the lowest levels of atrial fibrillation ever reported, 1/20 to ~1/6 of rates in high-income countries. These findings provide additional evidence that a subsistence lifestyle with high levels of physical activity, and a diet low in processed carbohydrates and fat is cardioprotective, despite frequent infection-induced inflammation. Findings suggest that atrial fibrillation is a modifiable lifestyle disease rather than an inevitable feature of cardiovascular aging.

Voluntary collective isolation as a best response to COVID-19 for indigenous populations? A case study and protocol from the Bolivian Amazon.

Indigenous communities worldwide share common features that make them especially vulnerable to the complications of and mortality from COVID-19. They also possess resilient attributes that can be leveraged to promote prevention efforts. How can indigenous communities best mitigate potential devastating effects of COVID-19? In Bolivia, where nearly half of all citizens claim indigenous origins, no specific guidelines have been outlined for indigenous communities inhabiting native communal territories. In this Public Health article, we describe collaborative efforts, as anthropologists, physicians, tribal leaders, and local officials, to develop and implement a multiphase COVID-19 prevention and containment plan focused on voluntary collective isolation and contact-tracing among Tsimane forager-horticulturalists in the Bolivian Amazon. Phase 1 involves education, outreach, and preparation, and phase 2 focuses on containment, patient management, and quarantine. Features of this plan might be exported and adapted to local circumstances elsewhere to prevent widespread mortality in indigenous communities.

Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study.

BACKGROUND: Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. METHODS: We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. FINDINGS: Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1-100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. INTERPRETATION: Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. FUNDING: National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

The Tres Ventanas Mummies of Peru.

The Tres Ventanas mummies of Peru are thought to be among the oldest mummies in existence, dating to between 8,000 and 10,000 years ago. A preliminary assessment is made of the potential of these mummies for use in future research on mummified remains. Although the Tres Ventanas cave and the four mummies were explored and then excavated by Frederic Engel in 1966-67, and the project is named in his honor as the "Engel Study Group", the importance of both the physical remains and the context in which they were found has only come to light in the last few years. Most important is the paleopathological examination of these remains, since these mummies are found in a high altitude area of Peru where adaptation to the limited partial pressure of oxygen is perhaps a key component in broadening our understanding of human diversity in past populations.

Computed tomographic evidence of atherosclerosis in the mummified remains of humans from around the world.

Although atherosclerosis is widely thought to be a disease of modernity, computed tomographic evidence of atherosclerosis has been found in the bodies of a large number of mummies. This article reviews the findings of atherosclerotic calcifications in the remains of ancient people-humans who lived across a very wide span of human history and over most of the inhabited globe. These people had a wide range of diets and lifestyles and traditional modern risk factors do not thoroughly explain the presence and easy detectability of this disease. Nontraditional risk factors such as the inhalation of cooking fire smoke and chronic infection or inflammation might have been important atherogenic factors in ancient times. Study of the genetic and environmental risk factors for atherosclerosis in ancient people may offer insights into this common modern disease.

Funerary artifacts, social status, and atherosclerosis in ancient peruvian mummy bundles.

BACKGROUND: Evidence of atherosclerotic plaques in ancient populations has led to the reconsideration of risk factors for heart disease and of the common belief that it is a disease of modern times. METHODS: Fifty-one wrapped mummy bundles excavated from the sites of Huallamarca, Pedreros, and Rinconada La Molina from the Puruchuco Museum collection in Lima, Peru, were scanned using computed tomography to investigate the presence of atherosclerosis. Funerary artifacts contained within the undisturbed mummy bundles were analyzed as an attempt to infer the social status of the individuals to correlate social status with evidence of heart disease in this ancient Peruvian group. This work also provides an inventory of the museum mummy collection to guide and facilitate future research. RESULTS: Statistical analysis concluded that there is little association between the types of grave goods contained within the bundles when the groups are pooled together. However, some patterns of artifact type, material, atherosclerosis, and sex emerge when the 3 excavation sites are analyzed separately. CONCLUSIONS: From the current sample, it would seem that social class is difficult to discern, but those from Huallamarca have the most markers of elite status. We had hypothesized that higher-status individuals may have had lifestyles that would place them at a higher risk for atherogenesis. There seems to be some indication of this within the site of Huallamarca, but it is inconclusive in the other 2 archeological sites. It is possible that a larger sample size in the future could reveal more statistically significant results.

Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

BACKGROUND: Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. METHODS: We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. FINDINGS: Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; p<0·0001) and with the number of arterial beds involved (mean age was 32 [SD 15] years for mummies with no atherosclerosis, 42 [10] years for those with atherosclerosis in one or two beds, and 44 [8] years for those with atherosclerosis in three to five beds; p<0·0001). INTERPRETATION: Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in premodern human beings raises the possibility of a more basic predisposition to the disease. FUNDING: National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Luke's Hospital Foundation of Kansas City.