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.

Preservation of the heart in ancient Egyptian mummies: A computed tomography investigation with focus on the myocardium.

The ancient Egyptians considered the heart to be the most important organ. The belief that the heart remained in the body is widespread in the archeological and paleopathological literature. The purpose of this study was to perform an overview of the preserved intrathoracic structures and thoracic and abdominal cavity filling, and to determine the prevalence and computed tomography (CT) characteristics of the myocardium in the preserved hearts of ancient Egyptian mummies. Whole-body CT examinations of 45 ancient Egyptian mummies (23 mummies from the Ägyptisches Museum und Papyrussammlung, Berlin, Germany, and 22 mummies from the Museo Egizio, Turin, Italy) were systematically assessed for preserved intrathoracic soft tissues including various anatomical components of the heart (pericardium, interventricular septum, four chambers, myocardium, valves). Additionally, evidence of evisceration and cavity filling was documented. In cases with identifiable myocardium, quantitative (measurements of thickness and density) and qualitative (description of the structure) assessment of the myocardial tissue was carried out. Heart structure was identified in 28 mummies (62%). In 33 mummies, CT findings demonstrated evisceration, with subsequent cavity filling in all but one case. Preserved myocardium was identified in nine mummies (five male, four female) as a mostly homogeneous, shrunken structure. The posterior wall of the myocardium had a mean maximum thickness of 3.6 mm (range 1.4-6.6 mm) and a mean minimum thickness of 1.0 mm (range 0.5-1.7 mm). The mean Hounsfield units (HU) of the myocardium at the posterior wall was 61 (range, 185-305). There was a strong correlation between the HU of the posterior wall of the myocardium and the mean HU of the muscles at the dorsal humerus (R = 0.77; p = 0.02). In two cases, there were postmortem changes in the myocardium, most probably due to insect infestation. To our knowledge, this is the first study to investigate the myocardium systematically on CT scans of ancient Egyptian mummies. Strong correlations between the densities of the myocardium and skeletal muscle indicated similar postmortem changes of the respective musculature during the mummification process within individual mummies. The distinct postmortem shrinking of the myocardium and the collapse of the left ventriclular cavity in several cases did not allow for paleopathological diagnoses such as myocardial scarring.

Coronary vascular dysfunction is associated with increased risk of death in patients with peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) and coronary vascular dysfunction are common in patients with cardiometabolic disease. Neither the prevalence of coronary vascular dysfunction among patients with PAD nor the prognostic impact with these two conditions present together has been well studied. METHODS: Consecutive patients who underwent PET MPI were analyzed for presence of coronary vascular dysfunction [myocardial blood flow reserve (MBFR) < 2]. Cox regression was used to examine the association of reduced MBFR with mortality in patients with PAD, as well as the association of comorbid MBFR < 2 and PAD with all-cause death. RESULTS: Among 13,940 patients, 1936 (14%) had PAD, 7782 (56%) had MBFR < 2 and 1346 (10%) had both PAD and MBFR < 2. Reduced MBFR was very common (69.5%) and was associated with increased risk of all-cause death (HR 1.69, 95%CI 1.32, 2.16, p < 0.01) in patients with PAD. Patients with both PAD and MBFR < 2, and those with either PAD or reduced MBFR had increased risk of death compared to those with neither condition: PAD + MBFR < 2 [(HR 95%CI), 2.30; 1.97-2.68], PAD + MBFR ≥ 2 (1.37; (1.08-1.72), PAD - MBFR < 2 (1.98; 1.75-2.25), p < 0.001 for all). CONCLUSION: Coronary vascular dysfunction was common in patients with PAD and was associated with increased risk of death.

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.

Reasons for discordance between positron emission tomography (PET) myocardial perfusion imaging (MPI) results and subsequent management.

BACKGROUND: Referral patterns to coronary angiography following positron emission tomography (PET) myocardial perfusion imaging (MPI) and reasons for non-referral following abnormal PET MPI are largely unknown. METHODS: Referral rates to coronary angiography within 90 days post PET MPI were determined. A random subset of 100 patients with severe (≥ 10%) ischemia on MPI between 2014-16 who were not referred for angiography were examined to better understand reasons as to why patients with high-risk MPI findings did not undergo coronary angiography. RESULTS: Among 19,282 unique patients, overall rate of 90-day coronary angiography was 18.5% (3574/19282). Among patients with severe ischemia, 64.1% (1930/3011) underwent angiography within 90 days; the rate was lower in those with mild-moderate (20.6% [1010/4898]) and no ischemia (5.6% [634/11373]). In the random sample of 100 patients, the most common physician reasons for non-referral were uncertainty regarding whether the test results were responsible for the patient's presenting symptoms, renal failure, and patient age, frailty, or cognitive status, while patient preference for medical management was by far the most common patient reason. CONCLUSION: Referral rates for coronary angiography after PET correlate with severity of ischemia. However, there appear to be opportunities to reconsider testing for instances when results will not change clinical management.

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.

Stress myocardial perfusion imaging in patients presenting with syncope: Comparison of PET vs. SPECT.

BACKGROUND: The role of myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD) presenting with syncope is controversial. We aimed to determine diagnostic yield of MPI for evaluation of syncope in patients without known CAD, as a function of pre-test patient risk and test modality (PET vs SPECT). METHODS: Between 1/2010 and 12/2016, 1324 consecutive patients presenting with syncope without known CAD underwent MPI with PET (n = 640) or SPECT (n = 684). Rates of abnormal MPI (summed difference score (SDS) > 2 or left ventricular ejection fraction (LVEF) reserve ≤ 0 for PET and SDS > 2 or post-stress LVEF ≤ 45% for SPECT) were determined among patients stratified by pre-test risk. In patients who were referred for coronary angiography, diagnostic yield of obstructive CAD was calculated in the overall cohort as well as in a propensity-matched cohort compared to patients without syncope. RESULTS: Abnormal MPI was noted in 36.5% (201/551) of patients who had PET compared with 13.0% (87/671) who had SPECT (P < 0.001), which is largely related to higher comorbidity burden and greater pre-test CAD risk in the PET population. Among patients who had an abnormal MPI, 8.5% (47/551) with PET and 0.7% (5/671) with SPECT were found to have obstructive CAD if referred for coronary angiography. Patients at intermediate-high pre-test risk had a higher proportion of abnormal MPIs and obstructive CAD as compared to those at low risk in both the PET and SPECT cohorts. The rate of abnormal testing and diagnostic yield of PET MPI was similar and proportionate to pre-test likelihood among matched patients with and without syncope. CONCLUSIONS: Among patients referred for PET MPI with syncope at an intermediate-high pre-test CAD risk, 1 in 3 had an abnormal MPI and 1 in 10 had obstructive CAD. The value of MPI was related to pre-test risk as opposed to the presence of syncope, and MPI testing with PET or SPECT in the low-risk population was low value.

Myocardial blood flow reserve assessed by positron emission tomography myocardial perfusion imaging identifies patients with a survival benefit from early revascularization.

AIMS: Positron emission tomography (PET) myocardial perfusion imaging (MPI) can non-invasively measure myocardial blood flow reserve (MBFR). We aimed to examine whether MBFR identifies patients with a survival benefit after revascularization, helping to guide post-test management. METHODS AND RESULTS: We examined all-cause mortality in 12 594 consecutive patients undergoing Rb82 rest/stress PET MPI from January 2010 to December 2016, after excluding those with cardiomyopathy, prior coronary artery bypass surgery (CABG), and missing MBFR. Myocardial blood flow reserve was calculated as the ratio of stress to rest absolute myocardial blood flow. A Cox model adjusted for patient and test characteristics, early revascularization (percutaneous coronary intervention or CABG ≤90 days of MPI), and the interaction between MBFR and early revascularization was developed to identify predictors of all-cause mortality. After a median follow-up of 3.2 years, 897 patients (7.1%) underwent early revascularization and 1699 patients (13.5%) died. Ischaemia was present in 4051 (32.3%) patients, with 1413 (11.2%) having ≥10% ischaemia. Mean MBFR was 2.0 ± 1.3, with MBFR <1.8 in 4836 (38.5%). After multivariable adjustment, every 0.1 unit decrease in MBFR was associated with 9% greater hazard of all-cause death (hazard ratio 1.09, 95% confidence interval 1.08-1.10; P < 0.001). There was a significant interaction between MBFR and early revascularization (P < 0.001); such that patients with MBFR ≤1.8 had a survival benefit with early revascularization, regardless of type of revascularization or level of ischaemia. CONCLUSION: Myocardial blood flow reserve on PET MPI is associated with all-cause mortality and can identify patients who receive a survival benefit with early revascularization compared to medical therapy. This may be used to guide revascularization, and prospective validation is needed.

Technetium pyrophosphate nuclear scintigraphy for cardiac amyloidosis: Imaging at 1 vs 3 hours and planar vs SPECT/CT.

BACKGROUND: Multi-societal consensus recommendations endorse both planar and single photon emission tomographic (SPECT) image acquisitions for the evaluation of cardiac amyloidosis. However, the correlation between planar and SPECT findings and the optimal timing of image acquisitions remain uncertain. METHODS: This is an analysis of 109 consecutive patients who underwent technetium pyrophosphate nuclear scintigraphy for the evaluation of cardiac amyloidosis. Patients were imaged at 1 and 3 hours after radiotracer injection using both planar and SPECT/CT, and the correlations between imaging protocols were compared. RESULTS: In the overall cohort (median age 77 years, 75% male), 33 patients had radiotracer localized to the myocardium on SPECT/CT images. There was strong correlation between 1- and 3-hour planar heart-to-contralateral lung ratios (mean difference 0.07, r = 0.94). However, there was discordance between planar image interpretation (based upon semiquantitative score and H/CL ratio) and myocardial localization of radiotracer on SPECT/CT in 17 patients (16%). The pattern of SPECT/CT uptake was identical at 1 and 3 hours in all cases (32 diffuse, 1 focal). CONCLUSION: These data support the recommendation that SPECT/CT should be obtained in addition to planar images when performing nuclear scintigraphy for the detection of cardiac amyloidosis. A 1-hour planar and SPECT/CT protocol appears optimal.

Drivers of radiation dose reduction with myocardial perfusion imaging: A large health system experience.

BACKGROUND: Despite increasing emphasis on reducing radiation exposure from myocardial perfusion imaging (MPI), the use of radiation-sparing practices (RSP) at nuclear laboratories remains limited. Defining real-world impact of RSPs on effective radiation dose (E) can potentially further motivate their adoption. METHODS: MPI studies performed between 1/2010 and 12/2016 within a single health system were included. Mean E was compared between sites with 'basic' RSP (defined as elimination of thallium-based protocols and use of stress-only (SO) imaging on conventional single photon emission computed tomography (SPECT) cameras) and those with 'advanced' capabilities (sites that additionally used solid-state detector (SSD) SPECT cameras, advanced post-processing software (APPS) or positron emission tomography (PET) imaging), after matching patients by age, gender, and weight. Contributions of individual RSP to E reduction were determined using multiple linear regression after adjusting for factors affecting tracer dose. RESULTS: Among 55,930 MPI studies performed, the use of advanced RSP was associated with significantly lower mean E compared to basic RSP (7 ± 5.6 mSv and 16 ± 5.4 mSv, respectively; P < 0.001), with a greater likelihood of achieving E < 9 mSv (65.7% vs. 10.8%, respectively; OR 15.8 [95% CI 14 to 17.8]; P < 0.0001). Main driver of E reduction was SO-SSD SPECT (mean reduction = 11.5 mSv), followed by use of SO-SPECT + APPS (mean reduction = 10.1 mSv), ;ET (mean reduction = 9.7 mSv); and elimination of thallium protocols (mean reduction = 9.1 mSv); P < 0.0001 for all comparisons. CONCLUSION: In a natural experiment with implementation of radiation-saving practices at a large health system, stress-only protocols used in conjunction with modern SPECT technologies, the use of PET and elimination of thallium-based protocols were associated with greatest reductions in radiation dose. Availability of several approaches to dose reduction within a health system can facilitate achievement of targeted radiation benchmarks in a greater number of performed studies.

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.

Is coronary calcium scoring too late? Total body arterial calcium burden in patients without known CAD and normal MPI.

BACKGROUND: Patients with normal myocardial perfusion imaging (MPI) have a good prognosis. However, pre-clinical coronary and extracoronary atherosclerosis may exist in the absence of myocardial ischemia. METHODS: 154 Egyptian patients (mean age 53 years) underwent whole-body non-contrast CT following normal MPI. RESULTS: Atherosclerosis in the form of calcification was observed in ≥1 vascular bed in 115 of 154 (75%) patients. This included the iliofemoral (62%), abdominal aorta (53%), thoracic aorta (47%), coronary (47%), and carotid (25%) vascular beds. Mean total body calcium score was 3172 ± 530 AU. Extracoronary atherosclerosis in patients with a zero coronary artery calcium (CAC) score was common, occurring in the above-listed beds 42%, 36%, 29%, and 7% of the time, respectively. CAC was rarely present without iliofemoral or abdominal aortic calcification. CONCLUSION: Quantitative assessment of calcification in different vascular beds demonstrates that extracoronary atherosclerosis is common in patients who have normal MPI. Atherosclerotic calcifications are most common in the iliofemoral arteries and abdominal aorta, which typically predate coronary calcifications. An imaging strategy to detect extracoronary atherosclerosis could lead to greater understanding of the natural history of atherosclerosis in its long pre-clinical phase and possibly to earlier preventive strategies.