INTRODUCTION
Alzheimer's disease (AD) is increasing in the Caribbean, especially for persons of African ancestry (PAA) and women. However, studies have mostly utilized surveys without AD biomarkers.
...METHODS
In the Tobago Health Study (n = 309; 109 women, mean age 70.3 ± 6.6), we assessed sex differences and risk factors for serum levels of phosphorylated tau‐181 (p‐tau181), amyloid‐beta (Aβ)42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Blood samples were from 2010 to 2013 for men and from 2019 to 2023 for women.
RESULTS
Women were more obese, hypertensive, and sedentary but reported less smoking and alcohol use than men (age‐adjusted p < 0.04). Compared to men, women had worse levels of AD biomarkers, with higher p‐tau181 and lower Aβ42/40, independent of covariates (p < 0.001). In sex‐stratified analyses, higher p‐tau181 was associated with older age in women and with hypertension in men. GFAP and NfL did not differ by sex.
DISCUSSION
Women had worse AD biomarkers than men, unexplained by age, cardiometabolic diseases, or lifestyle. Studying risk factors for AD in PAA is warranted, especially for women earlier in life.
Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D ...among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of anti-diabetic medication during a mean follow-up 7.9 ± 1.1 years. Among offspring (n=1105) and spouses (n=328) aged 45-64 years without T2D at baseline visit, the annual incident rate of T2D was 3.6 and 3.0 per 1000 person-years, respectively, while among offspring (n=444) and spouses (n=153) aged 65+ years without T2D at baseline, the annual incident rate of T2D was 7.2 and 7.4 per 1000 person-years, respectively. By comparison, the annual incident rate of T2D per 1000 person-years in the U.S. general population was 9.9 among those aged 45-64, and 8.8 among those aged 65+ years (2018 National Health Interview Survey). Baseline BMI, waist circumference, and fasting serum triglycerides were positively associated with incident T2D, whereas fasting serum HDL-C, adiponectin, and sex hormone binding globulin were protective against incident T2D among the offspring (all P<0.05). Similar associations were observed among their spouses (all P<0.05, except sex hormone binding globulin). In addition, we observed that among spouses, but not offspring, fasting serum interleukin 6 and insulin-like growth factor 1 were positively associated with incident T2D (P<0.05 for both). Our study suggests that both offspring of long-living individuals and their spouses, especially middle-aged, share a similar low risk for developing T2D as compared with the general population. Our findings also raise the possibility that distinct biological risk and protective factors may contribute to T2D risk among offspring of long-lived individuals when compared with their spouses. Future studies are needed to identify the mechanisms underlying low T2D risk among the offspring of individuals with exceptional longevity, and also among their spouses.
Abstract
Emerging evidence indicates that ectopic skeletal muscle adiposity may be a risk factor for type 2 diabetes (T2D), especially in persons of African ancestry. In vitro studies suggest that a ...Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1), plays a role in adiposity regulation and could be a biomarker for adiposity in humans. The objective of this study was to test whether serum DKK1 levels relate to adiposity measures in a cohort from an African ancestry population at high risk for T2D. Fasting serum DKK1 was measured in a sample of 159 men of African ancestry aged ≥40 years (mean age ± SD, 63.5 ± 8.2 years; mean body mass index, 27.8 ± 4.5 kg/m2). Anthropometrics included total-body and trunk adiposity measured by dual-energy x-ray absorptiometry and lower-leg skeletal muscle density measured by CT which reflects the intramuscular adiposity content (mg/cm3). Serum DKK1 was positively correlated with BMI (r = 0.20; P = 0.01), waist circumference (r = 0.15; P = 0.046), DXA total-body adiposity (r = 0.24; P = 0.003), and DXA trunk adiposity (r = 0.21; P = 0.009), independent of age and height. In addition, serum DKK1 was inversely correlated with skeletal muscle density (r = −0.25; P = 0.002), independent of age, BMI, and calf muscle area. No significant correlation was found between serum DKK1 and fasting serum glucose or insulin levels or insulin resistance estimated by homeostasis model assessment. These findings suggest that higher levels of serum DKK1 may be associated with greater overall, central, and ectopic skeletal muscle adiposity. Further studies are needed to unravel the potential role of DKK1 in the regulation of adiposity in humans.
Abstract only While type 2 diabetes (T2D) is a known risk factor for the acceleration of muscle loss with aging, less is known about the impact of T2D on skeletal muscle fat infiltration (i.e., ...myosteatosis) and overall adiposity. Myosteatosis increases with aging, is greater in African as compared to European ancestry individuals, and plays an important role in the development of T2D. Thus, we investigated the association of T2D with changes in body adiposity distribution, with a particular interest in myosteatosis. T2D was identified by self-report, use of hypoglycemic agents, or fasting glucose levels of ≥ 126 mg/dL. Longitudinal changes in computed tomography-measured calf skeletal muscle density as an inverse surrogate measure of intramuscular adiposity (mg/cm 3 ) and dual-energy X-ray absorptiometry-measured regional and whole body fat were examined by T2D status over an average of 6 years in 724 African-Caribbean men aged 40-54 years from the Tobago Health Study. Total body, arm, leg, and trunk adiposity increased to a significantly greater extent among men without compared to with T2D. In contrast, men with T2D had a 1.6 times greater decrease in calf skeletal muscle density compared with their non-diabetic counterparts (p=0.03). T2D is associated with lower gains in general adiposity, but an increased gain in skeletal muscle adiposity among middle aged African Caribbean men. Our novel findings suggest that middle-aged African Caribbean men with T2D might be at especially high risk for increased gain of myosteatosis. Interventions targeted for men in this age group could focus on controlling diabetes, slowing myosteatosis, and promoting healthy aging.
Abstract only Increased skeletal muscle fat infiltration (i.e. myosteatosis) is now recognized as a major risk factor for cardio-metabolic diseases. Therefore, a lifestyle modification that reduces ...myosteatosis would be of great public health importance. However, studies examining the association of relevant lifestyle factors with this ectopic fat depot are lacking, particularly in African ancestry populations who have a very high burden of cardio-metabolic diseases. The aim of this study was to examine the relation between objectively measured physical activity and sedentary behavior with computed tomography measured calf muscle attenuation among middle-aged and elderly African-Caribbeans from the population-based Tobago Health Study. Preliminary analyses were conducted among 134 women (mean age 59 yrs, mean BMI 31.6 kg/m 2 ) and 355 men (mean age 62 yrs, mean BMI 28 kg/m 2 ). Physical activity was measured using the SenseWear Pro armband worn for 4-7 days. We calculated the mean duration of waking time engaged in light physical activity (LPA), moderate to vigorous activity (MVPA), and sedentary behavior (SB) per day. Skeletal muscle attenuation (mg/cm 3 ) reflects the fat content of the muscle such that greater skeletal muscle fat infiltration is reflected by lower attenuation. Women spent less time in LPA (146 vs. 270 min/day) and MVPA (15 vs. 41 min/day), but more time in SB (789 vs. 647 min/day) than men (all p<0.0001) after adjustments for gender differences in age. Muscle attenuation was lower among women compared with men (70.5 vs. 72.7 mg/cm3; age and BMI adjusted p<0.0001). In both women and men, muscle attenuation was positively correlated with the LPA and MVPA, and inversely with time spent in SB (spearman correlation coefficients (r) ranged from 0.21 to 0.39, all p<0.006 adjusted for age). Upon additional adjustment for BMI, in both women and men, the association of muscle attenuation with MVPA remained significant (r=0.21 and r=0.18, respectively, both p<0.03), but there was no association with LPA. Percent time spent in SB was associated with muscle attenuation only among women after additional adjustment for BMI (women: -0.16, p=0.052), and we also found a significant sex interaction effect of SB on muscle attenuation (p=0.035). Our preliminary findings suggest that there is significant association between MVPA and myosteatosis among middle-aged and elderly African Caribbeans. However, SB may only be relevant for myosteatosis among women. Future analyses will be conducted in a larger sample from this cohort to confirm our findings and to test for independence from other potential confounding factors, such as diet, sleep patterns, adiposity distribution, and diabetes.
Abstract only Objective: Pregnancy and parity (number of children born to a women) are associated with alterations in metabolism and lifestyle, which may affect women’s short- and long-term ...cardiometabolic health. Greater skeletal muscle adiposity (myosteatosis) is recognized as a major risk factor for cardiometabolic diseases, especially in African ancestry individuals. While lifetime parity has been previously associated with greater central obesity years after childbearing ceased, it remains unclear whether parity is associated with myosteatosis. Methods: We examined the association of parity (0, 1, 2, 3, 4+) with myosteatosis and general and central obesity among 1,119 African Caribbean women, aged 40-84 years, recruited from 2019 to 2023 without regard to health status. Calf myosteatosis area was measured by CT-derived intermuscular adipose tissue (IMAT, mm 2 ) and skeletal muscle density (mg/cm 3 , with a lower density indicating more adiposity). Multivariable linear regression models were used to estimate the adjusted means of IMAT, muscle density, BMI, and waist circumference for each parity group. Results: The mean age of women who reported ever being pregnant (N=969) was 55.8 (SD=9.0) years. They were obese on average (BMI=32.1 (SD=6.8) kg/m 2 ), and had given birth to an average of 3 (SD=2.3) children. In multivariable models, higher parity was significantly associated with higher IMAT and lower muscle density, after accounting for age, BMI, physical activity, and comorbidities (see Table). Parity showed no associations with BMI or waist circumference. Conclusions: Parity may be associated with greater accumulation of adiposity in skeletal muscle, despite no link with general or central adiposity among African Caribbean women. Our novel findings, if confirmed in prospective studies, might highlight the need for tailored strategies for maintaining healthy muscles in multiparous women of African ancestry. Table. Adjusted population marginal means (95% CI) for myosteatosis by parity groups in African Caribbean women a
Abstract only Introduction: Skeletal muscle adipose tissue infiltration (i.e. myosteatosis) increases with age and is considered a significant risk factor for cardio-metabolic diseases. Emerging data ...hint at its role in cognitive decline, but largely from cross-sectional studies in White populations. Longitudinal studies including Black populations, who have a higher risk of both myosteatosis and Alzheimer’s Disease and related dementias than Whites, are warranted. Aim: Determine the association between abdominal myosteatosis with cognitive function in a cohort of White and Black American men (n=1,095; 42.1% Black) and women (n=1,450; 49.1% Black) from the Coronary Artery Risk Development in Young Adults (CARDIA), and whether associations vary by race and sex. We included those with baseline (Year 25, 2010-11) and 5-year follow-up (Year 30, 2015-16) cognitive assessment. Methods: Computed Tomography measured abdominal intermuscular adipose tissue (IMAT) volume. Cognition assessed by the Digit Symbol Substitution Test (DSST). Linear regression used to assess the cross-sectional and longitudinal (Year 30-Year 25 DSST score) associations of IMAT with cognitive function after adjusting for age, sex, race, center, education, height, follow-up-time, and baseline DSST score (longitudinal models). IMAT was log-transformed, and results were standardized with effects shown per standard deviation (SD). Sex and race interactions with IMAT were statistically significant. Results: Overall, participants were 50.2 (3.6) years old, with a BMI of 30.2 (7.1) kg/m 2 , IMAT of 4.9 (0.6) cm 3 , DSST score of 70.6 (15.8) and 5-year change in DSST score of -2.5 (9.3). Compared to men, women had higher BMI, lower IMAT, and higher baseline DSST scores (p-values<0.001), yet a 5-year change in DSST score between sexes was not significantly different (both β=-2.5, p-value=0.94). By race, Blacks had higher BMI, lower IMAT, lower DSST score, and greater DSST score decline than Whites (-3.0 (9.3) and -2.1 (9.3), respectively) (p-values<0.05). Longitudinally, higher IMAT predicted significant DSST decline in women (5-year decrease in DSST score β=-0.68 points for 1 SD of log IMAT, p-value<0.05) but not in men (β=-0.24, p-value=0.345). By race, higher IMAT was associated with significant decline in DSST score in Whites (5-year decrease in DSST: β=-0.79 points for 1 SD of log IMAT, p-value=<0.01) but not in Blacks (β=-0.18, p-value=0.497). Conclusions: Abdominal myosteatosis may be a novel risk factor for cognitive decline, especially in women and Whites. Future studies using an expanded battery of cognitive tests and longer follow-ups are warranted to further advance our understanding of the novel role of myosteatosis in dementia risk.
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