Abstract only Introduction: Skeletal muscle adipose tissue infiltration (i.e. myosteatosis) increases with aging, and is recognized as a major risk factor for cardio-metabolic diseases. While it is ...known that visceral adiposity is related to dementia and cognitive decline, the relationship between myosteatosis and cognition is not well understood. Such studies are particularly needed among African ancestry women, who have greater myosteatosis and higher burden of Alzheimer’s Disease and Related Dementias compared with White women. Aim: The objective of this study was to assess if, among African Caribbean middle-aged and older women (aged 40-79), myosteatosis is associated with cognitive function. Methods: Data were collected on women (n=481) from the Tobago Health Study. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a test of information processing speed; DSST is a fast, reliable and sensitive test that predicts onset of dementia. DSST was administered to participants by trained interviewers; scores ranged from 0 to 81 (lower score indicating cognitive decline). Peripheral Quantitative Computed Tomography (Stratec XCT-2000) was used to measure calf skeletal muscle density (MD), which was used as a proxy measure for the myosteatosis (lower MD reflects more adiposity). Linear regression was used to assess the association of muscle density with cognition and was adjusted for age, education, muscle area, waist circumference, alcohol intake, smoking, walking hours, diabetes and hypertension. Results for the primary predictor of interest (MD) were standardized with effects shown per standard deviation (SD). Results: Mean (SD) DSST scores were 38.8 (13.2). Overall, participants were aged 55.2 years and had a BMI of 30.7 kg/m 2 . Mean (SD) MD was 71.7((5.3) (mg/cm 3 ). As expected, in unadjusted analyses, the strongest predictors of lower DSST scores in these women were older age and lower education, higher waist circumference, diabetes and hypertension. After full adjustment, we found that a one SD increase in MD was associated with a 1.48 increase in DSST score (p-value=0.015). Conclusions: Our findings suggest that in African Caribbean women, greater myosteatosis is associated with slower information processing speed, an early indicator of future dementia risk. Future studies using expanded battery of cognitive tests and longitudinal follow-up are warranted to further advance our understanding of the novel role of myosteatosis in dementia risk among African ancestry women.
Abstract only Introduction: Skeletal muscle is the largest organ in the human body and vital to maintaining metabolic homeostasis. Increased skeletal muscle fat infiltration (i.e. myosteatosis) is ...now recognized as a major risk factor for cardio-metabolic diseases, independent of general obesity. Modifications in lifestyle, such as sleep, to reduce myosteatosis would be of great public health importance. However, studies of this relationship often use subjective data and are lacking in minority populations. The aim of this study was to examine the relation between objectively measured sleep duration and myosteatosis at the calf among African Caribbeans. Methods: Data were collected on men (n=393) and women (n=438) from the Tobago Health Study. Sleep duration and physical activity was collected using a SenseWear Pro Armband (BodyMedia, Inc.). Participants were instructed to wear the armband at all times, except in water, for 4-7 days. Measures of muscle density, intermuscular adipose tissue (IMAT), and area were obtained by peripheral QCT scans of the calf (Stratec XCT-2000). Model covariates included age, sex, BMI, diabetes, alcohol intake, smoking, and moderate to vigorous physical activity (MVPA). Linear regression was used to assess the relationship of sleep duration on skeletal muscle. Results: Mean sleep duration was 5.5 hours/day (Min 2.2, Max 11.6). Overall, participants were aged 58.7 years, had a BMI of 30.2 kg/m 2 , spent an average of 42 min/day in MVPA, and 18% were diabetic. In fully adjusted models, longer sleep duration was associated with smaller muscle area, but greater muscle density and less IMAT (all P<0.03). There was no interaction of sleep and sex on muscle density, area and IMAT (p-value=0.5184; 0.2730; 0.0954). Conclusions: In African Caribbean men and women, longer sleep duration was associated with less myosteatosis, as well as, less muscle area at the calf. Further research is warranted to understand this relationship longitudinally in order to determine how it may inform lifestyle guidelines in the Caribbean.
Abstract only Introduction: The population of Tobago is a unique African-ancestry population with a high prevalence of chronic disease, including hypertension and obesity. These conditions are ...associated with abnormalities in cardiac structure and function that confer an increased risk of heart failure. However, the distribution and correlates of these abnormalities have not been described in Tobagonian women, or any Afro-Caribbean population. Hypothesis: Abnormalities in cardiac structure and function will correlate with BMI and blood pressure. Methods: Participants from the Tobago Women’s Study aged 45+ were recruited for the Tobago Heart Study without regard to health status. Participants underwent transthoracic echocardiography, a health history, clinical examination, and blood draw. Hypertension was defined by blood pressure measures or prescription of relevant medication. The eventual recruitment goal is 900 men and women; the current analysis is a preliminary assessment of 376 women with data currently available. Statistical analyses included descriptive statistics and Spearman correlations. Results: The mean age of the study sample was 60.8 years (range 46-79). The prevalence of hypertension and obesity were 76.2% and 60.1%, respectively. Abnormalities in cardiac structure were detected in 77.5% of participants (of these, 87.9% concentric remodeling, 9.4% concentric hypertrophy, 2.7% eccentric hypertrophy). Diastolic dysfunction was present in 13.6% of participants (of these, 83.7% grade I, 14.3% grade II, and 2.0% grade III dysfunction); cardiomyopathy was found in 1.9%. Results of Spearman correlations are shown in Table 1. Conclusion: In a population of Tobagonian women, a low prevalence of diastolic dysfunction was observed despite highly prevalent abnormal left ventricle geometry. Blood pressure and BMI are important correlates of cardiac structure and function in this understudied population. In future analyses these results will be updated with greater sample size and compared to findings in men.
Abstract only Introduction: Alcohol intake and ectopic fat are associated with cardiometabolic diseases. While previous studies primarily focused on visceral and/or liver fat, few studies to date ...have investigated the associations of alcohol intake with skeletal muscle fat infiltration, a fat depot which might contribute to the increased risk of diabetes and hypertension in African ancestry populations. Methods: Alcohol intake (drinks/day) was assessed using a 146-item semi-quantitative food frequency questionnaire in the Tobago Health Study (N=800). Ectopic fat was measured in the abdomen and thigh in a subset of this cohort (N=706, mean age=63.94 (8.66) years, mean BMI=27.72 (4.65) kg/m 2 ) using computed tomography. Men were divided into current drinkers/not current drinkers, and the current drinkers were further subdivided into types of alcohol consumed (wine, beer/stout, or liquor). Results: A majority of men (56.1%) were not current drinkers. Of drinking men, 76.1% were light drinkers (<1 drink/day), 17.4% were moderate drinkers (1-3 drinks/day), and 6.5% were heavy drinkers (>3 drinks/day). Men who did not drink were slightly older (65.1 vs 62.5, p<0.001), with less visceral adiposity (91.4 vs. 101.9 cm 3 , p=0.002) and less psoas muscle fat (0.59 vs 0.64 cm 3 , p=0.017) than men who drank, independent of age. In fully adjusted models, drinking liquor was positively associated with BMI, waist circumference, visceral and subcutaneous adiposity, while drinking beer was positively associated with thigh muscle fat (Table). Conclusion: Alcohol intake was associated with greater ectopic fat accumulation in all studied compartments, except in the liver, in this cohort of African Caribbean men, who mostly had low alcohol consumption. We also report a novel finding that observed relationships differ by type of alcohol. † Adjusted for total energy intake, age, walking (hours/week), TV watching (≥14 hours/week), current smoking, diabetes, hypertension, and statin use status. * Additional adjustment for BMIHU = Houndsfield Units
Abstract
Although the connection between type 2 diabetes (T2D) and dementia is known, it is less clear whether this relationship extends to cognitive decline. Our aim was to examine whether baseline ...fasting plasma glucose, insulin, HOMA-IR, and HbA1c, and T2D status predict cognitive decline in a multicenter cohort study of families with a clustering of exceptional survival. We analyzed change across five cognitive tests collected over 7.9 years: Mini-Mental State Examination, Digit Span, Logical Memory, Animal Fluency and Digit Symbol Substitution. Among 2,175 family members (mean age 63±11 years (range 32-100); 54% women), 39.8% had prediabetes and 6.8% had T2D. Multiple linear mixed models were adjusted for age, sex, field center, education, APOEε4 status, BMI and family relatedness. A trend was observed for immediate (p=0.047) and delayed (p=0.037) memory, with normal glucose tolerance (NGT) predicting increased scores, prediabetes showing no change, and T2D predicting decreased scores. Among those without T2D (N=2,026), each standard deviation (SD) higher glucose (11.5 mg/dl) was related to a greater decline in delayed memory (-0.34±0.16mg/dl; p=0.032), each SD higher HbA1c (0.32%) was related to a greater decline in immediate (-0.36±0.15 mg/dl; p=0.016) and delayed (-0.31±0.16 %; p=0.05) memory, while each SD higher HOMA-IR (1.5) was related to a greater decline in Digit Span Backwards (-0.13±0.06; p=0.047). Findings suggest that among individuals with a clustering of exceptional survival, T2D, glucose, and HbA1c may predict greater decline in episodic memory, an ability typically affected early in Alzheimer dementia. The possible mechanisms, including genetic and metabolic mediators, warrant further investigation.
Abstract only Introduction: Sleep efficiency (or sleep continuity, i.e., a ratio of time spent sleeping to time spent in bed), is inversely associated with hypertension, impaired glucose metabolism, ...CVD risk, and mortality risk. Prolonged sedentary behavior and physical activity are independently associated with sleep efficiency. However, it is not well documented how substituting time in sedentary behavior with physical activity affects sleep efficiency, especially among African-ancestry populations, who are at high risk for CVD. Aim: To determine if displacement of sedentary time with activity was cross-sectionally associated with higher sleep efficiency among African Caribbean men (n=231) and women (n=668) from the Tobago Health Study. Methods: Sleep efficiency, sedentary behavior (SB), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were collected using a SenseWear Pro Armband. Participants wore the armband at all times, except in water, for 4-7 days. We used the Isotemporal Substitution Framework paired with linear regression to examine associations of SB, LPA and MVPA with sleep efficiency adjusting for age, education, BMI, hypertension, diabetes, smoking, alcohol consumption, caffeine intake, and sleep medication. Results: Men (mean age ± Standard deviation: 63.2 ± 8.2 years; mean BMI 28.2 ± 4.8 kg/m 2 ) spent on average less time in SB (12.4 ± 2.9 hours/day) and more time in LPA (4.7 ± 2.1 hours /day) and MVPA (0.92 ± 0.88 hours/day) than women (mean age 55.6 ± 8.7 years; mean BMI 31.8 ± 6.4 kg/m 2 ) (all p-vales <0.001). Men had lower sleep efficiency (74.6% ± 10.4) than women (81.2% ± 0.96; p-value <0.001). Cross-sectionally reallocating 1 hour of SB with LPA was associated with a 1% higher sleep efficiency (p-value=0.016) in men and with a 0.37% higher sleep efficiency in women (p-value=0.074). In men, reallocating 1 hour of SB with MVPA and 1 hour of LPA with MVPA were significantly associated with lower sleep efficiency -1.9% (p-value=0.014) and -2.8% (p-value=0.017), respectively; in women these associations were not statistically significant. Interaction term for sex and sleep efficiency was statistically significant (p-value <0.0001). Conclusions: In this population with short sleep duration, reallocating 1 hour of SB with LPA was associated with higher sleep efficiency in both genders. In contrast, among men only, reallocating 1 hour of SB to MVPA and 1 hour of LPA to MVPA were unexpectedly associated with lower sleep efficiency. Further research is warranted to understand these relationships longitudinally to determine how truly replacing SB for activities of different intensities impacts sleep health, which could then potentially inform lifestyle guidelines in older Caribbeans. In this highly sedentary population, interventions aimed at increasing LPA may be easier to implement and maintain and provide greater sleep and overall health benefit.
Abstract only During the aging process, the vasculature undergoes pathologic changes which are strongly associated with hypertension and future cardiovascular disease (CVD) risk. Previous work to ...identify protein biomarkers of these subclinical vascular changes, which have largely focused on single proteins, has observed many associations in different populations. However, research in African-ancestry populations, who are at high risk for hypertensive CVD, is limited and may be biased by the existing research in Whites. Therefore, we used a proteomic approach to identify biomarkers of vascular aging as assessed by pulse-wave velocity (PWV) and abdominal aortic calcification (AAC). We included 346 African-ancestry men from the Tobago Health Study, a prospective cohort study of community-dwelling men aged ≥40 years residing on the Caribbean island of Tobago. These men were aged from 53-89 years old (mean ± SD = 63.4 ± 8.1 years) and were overweight on average (mean ± SD BMI = 27.7 ± 4.3kg/m2). 79.2% of men had hypertension, 24.6% had diabetes, and 5.9% were current smokers. We quantified protein expression using the Olink® Target 96 Cardiovascular III proteomics panel which includes 92 proteins with known association to human cardiovascular processes (CVDIII; Olink®, Waltham, MA). Brachial-ankle PWV (cm/s) was measured using an automated waveform analyzer. AAC was measured in the aorta at the iliac bifurcation via CT and scored using the Agatston method. Partial Spearman correlations were calculated to assess the relationship between each protein biomarker and both vascular aging outcomes adjusting for age, Olink® assay batch, height, weight, diabetes status, hypertension status, and current smoking. There were 13 and 5 proteins correlated with PWV and AAC, respectively (at P<0.05). All correlations were in the direct direction of effect. Only one protein, cystatin B, was correlated with both PWV and AAC (r= 0.17 and 0.12, P=0.002 and 0.03; respectively). After applying false discovery rate adjustment for multiple comparisons, only fatty acid binding protein 4 (FABP4) and PWV remained significant (r=0.18, P=0.046). In general, proteins categorized by Olink® as belonging to the inflammatory pathway were most likely to be correlated with PWV; whereas, those in the hormone response pathway were most frequently correlated with AAC. Our results highlight that FABP4, a protein related to atherosclerosis via inflammation, may also be an important marker of arterial stiffening in these African-ancestry men. Additionally, we identified cystatin B, a member of the cathepsin protease pathway, as a strong correlate of both PWV and AAC, which may warrant further research into it as a novel biomarker of vascular aging and CVD in this high-risk population. In conclusion, proteomics may be an effective tool for evaluating and identifying novel markers of vascular aging and CVD in underrepresented populations.
Objective
Skeletal muscle fat infiltration (known as myosteatosis) is greater in African compared with European ancestry men and may play an important role in the development of type 2 diabetes ...(T2D). However, prospective studies examining the magnitude of changes in myosteatosis with aging and their metabolic consequences are sparse.
Methods
Longitudinal changes in peripheral quantitative computed tomography measured calf myosteatosis intermuscular fat (mm2) and skeletal muscle density as a measure of intramuscular fat (mg/cm3) were examined in 1515 Afro‐Caribbean men aged 40+ years recruited without regard to their health status.
Results
During an average of 6.2 years of follow‐up, an age‐related increase in intermuscular fat and a decrease in skeletal muscle density were observed (all P < 0.0001), which remained significant in those who lost weight, gained weight, or remained weight stable (all P < 0.0001). In addition, muscle density loss accelerated with increasing age (P < 0.0001). Increased intermuscular fat during follow‐up was associated with an increased incident risk of T2D independent of factors known to be associated with T2D (odds ratios per 1‐SD increase in intermuscular fat = 1.29; 95% CI = 1.08‐1.53).
Conclusions
Our findings suggest that both inter‐ and intramuscular fat increase with advancing age and that intermuscular fat contributes to development of T2D among African ancestry men.
Grip strength is a robust indicator of overall health, is moderately heritable, and predicts longevity in older adults.
Using genome-wide linkage analysis, we identified a novel locus on chromosome ...18p (mega-basepair region: 3.4 - 4.0) linked to grip strength in 3755 individuals from 582 families aged 64 ± 12 years (range 30-110 years; 55% women). There were 26 families that contributed to the linkage peak (cumulative logarithm of the odds LOD score = 10.94), with six families (119 individuals) accounting for most of the linkage signal (LOD = 6.4). In these 6 families, using whole genome sequencing data, we performed association analyses between the 7312 single nucleotide (SNVs) and insertion deletion (INDELs) variants in the linkage region and grip strength. Models were adjusted for age, age2, sex, height, field center, and population substructure.
We found significant associations between genetic variants (8 SNVs and 4 INDELs, p<5*10-5) in the Disks Large-associated Protein 1 (DLGAP1) gene and grip strength. Haplotypes constructed using these variants explained up to 98.1% of the LOD score. Finally, RNAseq data showed that these variants were significantly associated with the expression of nearby Myosin Light Chain 12A (MYL12A), Structural Maintenance of Chromosomes Flexible Hinge Domain Containing 1 (SMCHD1), Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) genes (p< .0004).
The DLGAP1 gene plays an important role in the post-synaptic density of neurons; thus, it is both a novel positional and biological candidate gene for follow-up studies aimed at uncovering genetic determinants of muscle strength.
The epidemiology of prediabetes and its metabolomic features remain poorly characterized in the oldest old. Therefore, we characterized the serum lipidome in 635 nonagenarians and centenarians ...without type 2 diabetes (T2D) from the Long Life Family Study, a multicenter study of 583 families with a clustering of exceptional longevity. Despite a low T2D prevalence and incidence in the LLFS cohort, 361 (56.9%) of participants aged 90+ years had prediabetes at study entry based on either glycated hemoglobin or fasting serum glucose levels. We used LC/MS to initially assess 193 lipid metabolites in fasting serum in those with and without prediabetes. We tested the association of log transformed lipid metabolites with prediabetes using logistic regression with the Benjamini-Hochberg false-discovery rate method (FDR<0.05) , while adjusting for age, sex, fasting time, field center, and familial relatedness. 17 out of 193 annotated lipid metabolites were associated with prevalent prediabetes, with the strongest association found for phosphatidylethanolamine (PE 40:7) , which remained significant after additional adjustment for BMI (odds ratio (OR) =2.83; 95% confidence interval (CI) : 1.7-4.7) . Phosphatidylethanolamine might have proinflammatory properties and act as a positive modulator of membrane disruption induced by islet amyloid polypeptide, an amyloidogenic protein involved in T2D. Our data suggest that among the oldest old with exceptional longevity prediabetes burden is high, and that the phosphatidylethanolamine pathway might have an important role in the development of prediabetes. Future untargeted metabolomic analyses will investigate potential biomarkers that predict the transition from prediabetes to diabetes among the oldest old in this unique family study of healthy aging and exceptional longevity.
Disclosure
I. Miljkovic: None. R. Cvejkus: None. P. An: None. B. Thyagarajan: n/a. J. Mengel-from: None. M. Feitosa: None. A. N. Benbourenane: None. J. M. Zmuda: None.
Funding
National Institute of Health (U01AG023746)
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