Opportunities, barriers, and recommendations in down syndrome research

Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy

MODERATION AND MEDIATION OF BODY COMPOSITION ON THE RELATIONSHIP BETWEEN PHYSICAL ACTIVITY AND ARTERIAL HEALTH

Brantley K. Ballenger, Sydni L. Carter, Grant Norman, Stamatis Agiovlasitis, FACSM. Mississippi State University, Mississippi State, MS. BACKGROUND: Cardiovascular disease is the leading cause of death in the United States. Physical activity (PA) levels and body fat percentage (%BF) contribute to cardiovascular disease risk, through increased arterial stiffness. However, the pathway of this relationship is not known. This study examined whether %BF moderates or mediates the relationships between PA or sedentary behavior levels with arterial stiffness. METHODS: Forty adults (19 men; age 27±10 yrs.) had carotid-femoral pulse wave velocity (CF-PWV) measured by applanation tonometry and %BF by bioelectrical impedance. Participants then wore a triaxial accelerometer on the non-dominant hip for 7 days to measure PA and sedentary behavior. Accelerometer data were scored with the Freedson cut points (Sedentary: ≤199 counts/min; Light ≤2690 counts/min; Moderate-to-vigorous: ≥2691 counts/min), allowing determination of percentage of time spent in sedentary (%Sedentary), light (%Light), and moderate-to-vigorous (%MVPA) PA levels. RESULTS: Pearson’s correlations showed significant associations between age, %BF, CF-PWV, and %Sedentary (r=.317-.732, p\u3c.05). However, %Light and %MVPA were not significantly associated with CF-PWV. The mediation analysis showed significant total effects of %Sedentary (β=.34, p=.034) and age (β=.73, p\u3c.001) on CF-PWV. %BF partially mediated the relationship between age and CF-PWV (β=.63, p\u3c.001), and fully mediated the relationship between %Sedentary and CF-PWV (β=.16, p=.29). Moderation analysis showed that the interaction of %BF and %Sedentary (R2=.31, p=.004), %Light (R2=.28, p=.007) and %MVPA (R2=.36, p=.001) significantly predicted CF-PWV. Furthermore, %BF significantly moderated the effect of %MVPA on CF-PWV (β=-.26, p=.049), but not %Sedentary or %Light. The effect of %MVPA on CF-PWV was greatest for those who were high (+1 SD) in %BF (β=-.60, p=.02), and moderate for those at the mean %BF (β=-.33, p=.04). CONCLUSION: %BF mediates the relationship between PA levels and arterial stiffness. Therefore, limiting sedentary behavior-by engaging in greater amounts of light or moderate-to-vigorous PA­-can reduce %BF. Reductions in %BF may lead to decreased arterial stiffness. Funding: Mississippi State University Office of Research and Economic Development and I’m An Athlete Foundatio

WRIST ACCELEROMETER CUT-POINTS FOR MEASURING PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOR IN ADULTS WITH DOWN SYNDROME

Morgan Bailey, Brantley K. Ballenger, Maggie Chamberlain, Stamatis Agiovlasitis, FACSM. Mississippi State University, Mississippi State, MS. BACKGROUND: The wrist may be an appropriate site for accelerometer placement for adults with Down syndrome (DS) because it may increase compliance. However, wrist accelerometer output has not been calibrated in adults with DS. This study therefore aimed to develop wrist worn accelerometer cut-points for sedentary behavior and moderate and vigorous physical activity for adults with DS. METHODS: Twenty-three adults with DS (11 men & 12 women; age 34 ± 8 years) performed 18 tasks each lasting 6 min: lying; sitting; watching a movie; playing app on tablet; drawing; standing; folding clothes; vacuuming; sweeping; moving a box; basketball; soccer; fitness circuit; dancing; walking at the preferred speed and at 0.8 and 1.4 m.s-1; and running. Rate of oxygen uptake was measured with portable indirect calorimetry (K5, Cosmed) and expressed as Metabolic Equivalents (METs). Vector Magnitude was determined based on output from a triaxial accelerometer (wGT3X-BT, Actigraph) worn on the non-dominant wrist. Vector Magnitude cut-points for sedentary behavior and moderate (3.0 - 5.99 METs) and vigorous (≥6 METs) physical activity were determined using Receiver Operating Characteristic (ROC) curves. Area under the ROC curve was used to evaluate overall classification performance of the models. Optimal cut-points maximizing sensitivity and specificity were selected based on Youden’s index. RESULTS: Area under the ROC curve was high for all models: (a) sedentary behavior (0.95; 95% CI: 0.93 - 0.97); (b) moderate physical activity (0.86; 95% CI: 0.82 - 0.89); and (c) vigorous physical activity (0.91; 95% CI: 0.84 - 0.97). The optimal Vector Magnitude cut-points were: (a) sedentary behavior ≤2680 counts∙min-1 (sensitivity 0.97; specificity 0.87; Youden’s index 0.84); (b) moderate physical activity ≤5013 counts∙min-1 (sensitivity 0.81; specificity 0.78; Youden’s index 0.59); and (c) vigorous physical activity ≥5458 counts∙min-1 (sensitivity 1.00; specificity 0.66; Youden’s index 0.66). CONCLUSION: This study offers DS-specific wrist-based accelerometer cut-points for classifying sedentary behavior and physical activity intensity in adults with DS. The cut-points appear to have high accuracy. Use of DS-specific cut-points may advance the study of physical activity and sedentary behavior in adults with DS. Funding: NIH Grant R15HD09866

PERIPHERAL AND CENTRAL ARTERIAL STIFFNESS AND HEMODYNAMICS IN ADULTS WITH AND WITHOUT DOWN SYNDROME

Grant Norman, Brantley K. Ballenger, Sydni L. Carter, Stamatis Agiovlasitis, FACSM. Mississippi State University, Mississippi State, MS. BACKGROUND: Adults with Down syndrome (DS) have decreased levels of arterial stiffness compared to same age peers without Down syndrome (non-DS). This is thought to be due to lower blood pressure among adults with DS. The purpose of this study was to compare central and peripheral arterial stiffness between adults with and without DS who were matched for age and blood pressure. METHODS: Seventeen adults with DS (age 38±9 yrs.; 10 men) and 17 adults without DS (age 36±11 yrs.; 7 men) underwent measurement of body composition by bioelectrical impedance. Central and peripheral arterial hemodynamics and stiffness were measured by carotid-femoral (CF-PWV) and carotid-radial pulse wave velocity (CR-PWV) analysis, respectively. Independent samples t-tests were performed to investigate differences between groups in hemodynamics, arterial stiffness, and augmentation index (AIx). RESULTS: No significant differences were present between groups for central or peripheral systolic blood pressure (p=.320; p=.194), diastolic blood pressure (p=.102), or mean arterial pressure (p=.251). Significant differences were present between groups for height (DS: 151±9 cm, non-DS: 172±12 cm, p\u3c.001), BMI (DS: 33±5 kg/m2, non-DS: 26±5 kg/m2, p\u3c.001), and body fat percentage (DS: 32±7%, non-DS: 27±9%, p=.042), but not for weight (DS: 77±13 kg, non-DS: 77±21 kg, p=.496). CF-PWV was significantly greater in non-DS (DS: 6±1 m/s, non-DS: 8±2 m/s, p=.012), but no differences were present between groups for CR-PWV (DS: 9±2 m/s, non-DS: 10±3 m/s, p=.139). Peripheral AIx was significantly greater in adults with DS (DS: 10±21 percent, non-DS: -7±20 percent, p=.012), but central AIx did not differ between groups (DS: 2±20 percent, non-DS: -8±21 percent, p=.088). CONCLUSION: Our findings confirm past research demonstrating lower central arterial stiffness in adults with than without DS. However, we found no difference between groups for peripheral arterial stiffness. These findings may be due to differences in body fat percentage or AIx between groups. Funding: Mississippi State University Office of Research and Economic Development and I’m An Athlete Foundatio