The effect of acute and 14-day exogenous ketone supplementation on glycemic control in adults with type 2 diabetes: two randomized controlled trials.

Acute ingestion of the exogenous ketone monoester supplement [(R)-3-hydroxybutyl-(R)-3-hydroxybutyrate] lowers blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, it is unknown how acute or repeated ingestion of exogenous ketones affects blood glucose control in individuals with type 2 diabetes (T2D). We conducted two randomized, counterbalanced, double-blind, placebo-controlled crossover trials to determine if 1) acute exogenous ketone monoester (0.3 g/kg body mass; N = 18) or 2) 14-day thrice daily premeal exogenous ketone monoester (15 g; N = 15) supplementation could lower blood glucose in individuals living with T2D. A single dose of the ketone monoester supplement elevated blood ß-OHB to ∼2 mM. There were no differences in the primary outcomes of plasma glucose concentration (acutely) or serum fructosamine (glycemic control across 14 days) between conditions. Ketone monoester ingestion acutely increased insulin and lowered nonesterified fatty acid concentrations; plasma metabolomics confirmed a reduction in multiple free fatty acids species and select gluconeogenic amino acids. In contrast, no changes were observed in fasting metabolic outcomes following 14 days of supplementation. In the context of these randomized controlled trials, acute or repeated ketone monoester ingestion in adults with T2D did not lower blood glucose when consumed acutely in a fasted state and did not improve glycemic control following thrice daily premeal ingestion across 14 days. Future studies exploring the mechanistic basis for the (lack of) glucose-lowering effect of exogenous ketone supplementation in T2D and other populations are warranted.NEW & NOTEWORTHY Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days.

Effect of the ketone beta-hydroxybutyrate on markers of inflammation and immune function in adults with type 2 diabetes.

Pre-clinical and cell culture evidence supports the role of the ketone beta-hydroxybutyrate (BHB) as an immunomodulatory molecule that may inhibit inflammatory signalling involved in several chronic diseases such as type 2 diabetes (T2D), but studies in humans are lacking. Therefore, we investigated the anti-inflammatory effect of BHB in humans across three clinical trials. To investigate if BHB suppressed pro-inflammatory cytokine secretion, we treated LPS-stimulated leukocytes from overnight-fasted adults at risk for T2D with BHB (Study 1). Next (Study 2), we investigated if exogenously raising BHB acutely in vivo by ketone monoester supplementation (KME) in adults with T2D would suppress pro-inflammatory plasma cytokines. In Study 3, we investigated the effect of BHB on inflammation via ex vivo treatment of LPS-stimulated leukocytes with BHB and in vivo thrice-daily pre-meal KME for 14 days in adults with T2D. Ex vivo treatment with BHB suppressed LPS-stimulated IL-1ß, TNF-α, and IL-6 secretion and increased IL-1RA and IL-10 (Study 1). Plasma IL-10 increased by 90 min following ingestion of a single dose of KME in T2D, which corresponded to peak blood BHB (Study 2). Finally, 14 days of thrice-daily KME ingestion did not significantly alter plasma cytokines or leukocyte subsets including monocyte and T-cell polarization (Study 3). However, direct treatment of leukocytes with BHB modulated TNF-α, IL-1ß, IFN-γ, and MCP-1 secretion in a time- and glucose-dependent manner (Study 3). Therefore, BHB appears to be anti-inflammatory in T2D, but this effect is transient and is modulated by the presence of disease, glycaemia, and exposure time.

Daily Affect and Daily Prospective Memory in People after Stroke and Their Partners: The Moderating Role of Resting Heart Rate.

INTRODUCTION: Experimental research suggests that affect may influence prospective memory performance, but real-life evidence on affect-prospective memory associations is limited. Moreover, most studies have examined the valence dimension of affect in understanding the influence of affect on cognitive performance in daily life, with insufficient consideration of the arousal dimension. To maximize ecological validity, the current study examined the relationships between daily affect and daily prospective memory using repeated daily assessments and the role of resting heart rate on these relationships. We examined both valence and arousal of daily affect by categorizing affect into four dimensions: high-arousal positive affect, low-arousal positive affect, high-arousal negative affect, and low-arousal negative affect. METHOD: We examined existing data collected from community-dwelling couples, of which at least one partner had a stroke history. The analytic sample included 111 adults (Mage = 67.46 years, SD = 9.64; 50% women) who provided 1,274 days of data. Among the participants, 58 were living with the effects of a stroke and 53 were partners. Participants completed daily event-based prospective memory tasks (in morning and/or evening questionnaires), reported daily affect in the evening, and wore a wrist-based Fitbit device to monitor resting heart rate over 14 consecutive days. RESULTS: Results from multilevel models show that, within persons, elevated high-arousal negative affect was associated with worse daily prospective memory performance. In addition, lower resting heart rate attenuated the inverse association between high-arousal negative affect and lowered prospective memory performance. We did not find significant associations of high- or low-arousal positive affect and low-arousal negative affect with daily prospective memory. DISCUSSION: Our findings are in line with the resource allocation model and the cue-utilization hypothesis in that high-arousal negative affect is detrimental to daily prospective memory performance. Lower resting heart rate may buffer individuals' prospective memory performance from the influence of high-arousal negative affect. These findings are consistent with the neurovisceral integration model on heart-brain connections, highlighting the possibility that cardiovascular fitness may help maintain prospective memory into older adulthood.

Establishing the minimal clinically important difference of the EQ-5D-3L in older adults with a history of falls.

PURPOSE: Establish the minimal clinically important difference (MCID) of a health-related quality of life (HRQoL) measure-the EuroQol EQ-5 Dimensions-3 Level (EQ-5D-3L)-in older adults with a history of falls. METHODS: This study is a secondary analysis of 255 complete cases who were enrolled in a 12-month randomized controlled trial (NCT01029171; NCT00323596); participants were randomized to the Otago Exercise Program (OEP; n = 126/172; Age:81.2 ± 6.2 years; 60.3% Female) or control (CON; n = 129/172; Age:81.7 ± 5.7 years; 70.5% Female). Participants completed the EQ-5D-3L and Visual Analogue Scale (VAS) at baseline and 1-year. The VAS was associated with HRQoL and was the health status anchor (VAS minimal improvement = 7 to 17, maximal improvement ≥ 18, minimal decline = - 7 to - 17, maximal decline ≤ - 18 points). We used four distinct approaches to estimate MCID ranges: (1) anchor-based change differences of the EQ-5D-3L (1-year minus baseline); (2) anchor-based beta coefficients from ordinary least squares regressions (OLS); (3) anchor-based receiver operating characteristic (ROC), and 4) distribution-based standard deviation and standardized effect size of 0.5. RESULTS: EQ-5D-3L MCID ranges for minimal improvements (OEP = 0.028 to 0.059; CON = 0.007 to 0.051), maximal improvements (OEP = 0.059 to 0.090; CON = 0.051 to 0.090), minimal declines (OEP = - 0.029 to - 0.105; CON = - 0.015 to - 0.051), and maximal declines (OEP = - 0.018 to - 0.072; CON = - 0.018 to - 0.082) were established using change difference, OLS, and distribution-based methods. The ROC area under the curve was poor, thus, it was not used to estimate the MCID. CONCLUSIONS: Our results will assist in the interpretation of changes in HRQoL, as measured by the EQ-5D-3L, in older adults with a history of falls.

Baseline health-related quality of life predicts falls: a secondary analysis of a randomized controlled trial.

PURPOSE: Among older adults, health-related quality of life (HRQoL) and falls are associated. Generic patient-reported outcomes measures (PROMs) assess individual's HRQoL. The role for PROMs, a potential tool for predicting subsequent falls, remains under-explored. Our primary aim was to determine whether a baseline PROMs assessment of HRQoL may be a useful tool for predicting future falls. METHODS: A secondary analysis of a 12-month randomized clinical trial (RCT) of a home-based exercise program among 344 adults (67% female), aged ≥ 70 years, with ≥ 1 falls in the prior year who were randomized (1:1) to either a home-based exercise program (n = 172) or usual care (n = 172). A negative binomial regression model with total falls count as the dependent variable evaluated the main effect of the independent variable-baseline HRQoL (measured by the Short-Form-6D)-controlling for total exposure time and experiment group (i.e., exercise or usual care) for the total sample. For the usual care group alone, the model controlled for total exposure time. RESULTS: For the total sample, the rate of subsequent total falls was significantly predicted by baseline HRQoL (IRR = 0.044; 95% CI [0.005-0.037]; p = .004). For the usual care group, findings were confirmed with wider confidence intervals and the rate of prospective total falls was significantly predicted by baseline HRQoL (IRR = 0.025; 95% CI [0.001-0.909]; p = .044). CONCLUSION: These findings suggest the ShortForm-6D should be considered as part of falls prevention screening strategies within a Falls Prevention Clinic setting. Trial Registrations ClinicalTrials.gov Protocol Registration System. Identifier: NCT01029171; URL: https://clinicaltrials.gov/ct2/show/NCT01029171 . Identifier: NCT00323596; URL: https://clinicaltrials.gov/ct2/show/NCT00323596 .

Minimal Clinically Important Difference of Executive Function Performance in Older Adults Who Fall: A Secondary Analysis of a Randomized Controlled Trial.

INTRODUCTION: Executive function is responsive to exercise and predictive of subsequent falls. Minimal clinically important differences (MCIDs) are critical for understanding whether observed changes are meaningful. However, MCIDs of many cognitive measures are not established. We aimed to determine MCIDs of the Digit Symbol Substitution Test ([DSST] processing speed measure), Stroop (inhibition measure), and Trail Making Test B-A (TMT; set-shifting measure), using anchor- and distribution-based approaches in older adults who have fallen and received the Otago Exercise Program (OEP) relative to usual care only (CON). Our secondary aim was to establish construct (convergent and divergent) validity of these measures. METHODS: Complete case analyses of cognitive outcomes (DSST, Stroop, TMT, and Montreal Cognitive Assessment [MoCA]) were acquired at baseline and 1 year (NCT01029171; NCT003235960); participants were randomized to the OEP (n = 114/172; Age: 80.6 ± 6.1 years; 64.9% Female) or CON (n = 128/172; Age: 82.3 ± 5.8 years; 71.9% Female)]. The MoCA was used as the anchor. We estimated MCIDs using anchor- and distribution-based approaches. Anchor-based executive function change differences ([CD] 1 year minus baseline) observed in participants with meaningful changes in the MoCA (≥3 or ≤ -3 points) receiving the OEP were subtracted from the CON. An anchor-based receiver operator characteristic (ROC) curve was employed to identify optimal cut-off scores of the 3 executive function measures. The distribution-based approach (DA) accounted for variability in baseline and follow-up data. MCID ranges were estimated using these approaches. We used Spearman's correlations to explore convergent validity between executive function measures and other measures involving the same construct (DSST, Stroop, TMT, MoCA, and Mini-Mental State Examination), and divergent validity between executive function measures and variables reflecting different constructs (Geriatric Depression Scale, Instrumental Activities of Daily Living, sex, and body mass index). RESULTS: Based on the 3 approaches, MCID improvement ranges were 3-5 symbols for the DSST (CD = 5; ROC = 2.5; DA = 3.3 symbols), and -11.5 to -26.0 s for the Stroop (CD = -26.0; ROC = -11.5; DA = -20.6 s). MCID decline ranges were -3 to -6 symbols for the DSST (CD = -5.2; ROC = -2.5; DA = -3.3 symbols) and 5.4-30.6 s for the Stroop (CD = 30.6; ROC = 5.4; DA = 20.6 s). MCIDs for the TMT were not meaningful due to high variability (Improvement: CD = -106.6; ROC = -18.4; DA = -69.1 s; Decline: CD = 69.1; ROC = 14.5; DA = 69.1 s). The executive function measures exhibited good convergent (r = -0.22 to r = 0.42) and divergent (r < -0.01 to r = 0.16) validity. CONCLUSIONS: These established MCIDs will allow clinicians to interpret meaningful changes in executive function following exercise amongst older adults who have fallen. The DSST, Stroop, and TMT demonstrated good construct validity, supporting their use in comprehensive fall-risk assessments in older adults who fall.

Having a Good Time Together: The Role of Companionship in Older Couples' Everyday Life.

INTRODUCTION: Companionship (i.e., enjoyable shared activities) is associated with higher emotional and relational well-being. However, the role of companionship for emotional well-being and relationship satisfaction in older couples' everyday life is not well understood. This article studies time-varying associations of companionship with emotional and relational well-being as older couples engage in their everyday life. METHODS: Participants provided three data points a day over 7 days using electronic surveys that were simultaneously completed by both partners. A total of 118 older heterosexual couples reported momentary companionship, positive and negative affect, and closeness. Data were analyzed using an intensive longitudinal dyadic score model. RESULTS: Couples with higher average companionship showed lower overall negative affect, more overall positive affect, and higher overall closeness. During moments of elevated momentary companionship, partners reported more positive affect, less negative affect, and higher closeness. Regarding between-couple partner differences, i.e., when the female partner's momentary companionship was higher on average than the male partner's momentary companionship, the female partner also showed less negative affect, more positive affect, and higher closeness than the male partner. During moments in which the female partner's momentary companionship was higher than the male partner's momentary companionship, the female partner showed less negative affect, more positive affect, and higher closeness than the male partner. DISCUSSION: Older couples show a consistent link between companionship and emotional well-being and closeness in everyday life emphasizing the importance of studying companionship in close relationships.

A rapid point-of-care ultrasound marker for muscle mass and muscle strength in older adults.

BACKGROUND/OBJECTIVES: Sarcopenia is defined as the gradual age-associated loss of both muscle quantity and strength in older adults, and is associated with increased mortality, falls, fractures and hospitalisations. Current sarcopenia criteria use dual-energy X-ray absorptiometry (DXA) measures of muscle mass, a test that cannot be performed at the bedside, unlike point-of-care ultrasound (PoCUS). We examined the association between ultrasonic measures of muscle thickness (MT, vastus medialis muscle thickness) and measures of muscle quantity and strength in older adults. METHODS: A total of 150 older adults (age ≥ 65; mean age 80.0 ± 0.5 years, 66 women, 84 men) were recruited sequentially from geriatric medicine clinics. Each subject had lean body mass (LBM, by bioimpedance assay), grip strength, mid-arm biceps circumference (MABC), gait speed and MT measured. All initial models were adjusted for biological sex. RESULTS: In our final parsimonious models, MT showed a strong significant correlation with all measures of muscle mass, including LBM (Standardised ß = 0.204 ± 0.058, R2 = 0.577, P < 0.001) and MABC (Standardised ß = 0.141 ± 0.067, R2 = 0.417, P = 0.038). With respect to measures of muscle quality, there was a strong significant correlation with grip strength (Standardised ß = 0.118 ± 0.115, R2 = 0.511, P < 0.001) but not with subject performance (gait speed). CONCLUSIONS: MT showed strong correlations with both measures of muscle mass (LBM and MABC) and with muscle strength (grip strength). Although more work needs to be done, PoCUS shows potential as a screening tool for sarcopenia in older adults.

Baroreflex function and postprandial hypotension in older adults.

PURPOSE: Postprandial hypotension (PPH) is a common but poorly understood etiology for fainting in older adults. One potential mechanism is age-related baroreflex dysfunction. We examined baroreflex function in older adults with PPH and without PPH (noPPH) during a standardized meal test. METHODS: 57 adults (age ≥ 65; 24 PPH, 33 noPPH, mean age 77.9 ± 0.9 years, 54% female) were recruited and had meal tests performed. The baroreflex effectiveness index (BEI, %) and baroreflex sensitivity (BRS, ms/mm Hg) were calculated using the sequence method. RESULTS: Baseline BEI (22 ± 2 versus 23 ± 2 percent, t = - 0.411, p = 0.682) and BRS (14.1 ± 2.4 versus 13.8 ± 2.5 ms/mm of Hg, t = - 0.084, p = 0.933) were similar in PPH and noPPH subjects. During the meal test PPH subjects showed significantly lower BEI as compared to noPPH subjects (time × PPH, F = 2.791, p = 0.042), while there was no difference in the postprandial change in BRS (time, F = 0.618, p = 0.605). CONCLUSION: Patients with PPH demonstrated an acute postprandial decrease in baroreflex effectiveness during meal testing as compared with normal subjects, suggesting a potential contributing mechanism for this condition.

Cortisol Synchrony in Older Couples: Daily Socioemotional Correlates and Interpersonal Differences.

OBJECTIVE: Social relationships can have positive and negative influences, and these associations are particularly pronounced in old age. This study focuses on everyday interpersonal physiological dynamics (cortisol synchrony) in older couples and investigates its associations with partner presence, positive daily partner interactions, and empathy. METHODS: We conducted coordinated multilevel analyses using data from two samples of older couples from Vancouver, Canada, and Berlin, Germany (study 1: n = 85 couples aged 60-87 years; study 2: n = 77 couples aged 66-85 years), who completed questionnaires and provided salivary cortisol samples five to seven times daily for 7 days. RESULTS: Significant dyadic covariation in cortisol (synchrony) was present across studies (study 1/2: b = 0.04/0.03, p < .001/.001). Partner presence was only associated with greater cortisol synchrony in study 1 (b = 0.06, p = .003) but not in study 2 (b = 0.02, p = .187). Cortisol synchrony was higher when partners reported prior positive socioemotional partner interactions (study 1: b = 0.09, p = .005; study 2: b = 0.04, p = .005). There was no statistically significant association between cortisol synchrony and empathic concern (b = 0.01, p = .590) or perspective taking (b = 0.02, p = .065). CONCLUSIONS: Moments of social bonding are intertwined with physiological synchrony in everyday life. The implications of potential repeated transmission of stress in the context of high synchrony for individual health and relationship functioning warrant further investigation.

Moving in Sync: Hourly Physical Activity and Sedentary Behavior are Synchronized in Couples.

BACKGROUND: Overall time spent in moderate-to-vigorous intensity physical activity (MVPA) and sedentary behavior are both correlated in couples. Knowledge about the nature and psychosocial correlates of such dyadic covariation could inform important avenues for physical activity promotion. PURPOSE: The present study investigates hour-by-hour covariation between partners (i.e., synchrony) in MVPA and sedentary behavior as partners engage in their daily lives and links it with person-level MVPA/sedentary behavior, temporal characteristics, and relationship variables. METHODS: We used 7-day accelerometer data from two couple studies (Study 1, n = 306 couples, aged 18-80 years; Study 2, n = 108 couples, aged 60-87 years) to estimate dyadic covariation in hourly MVPA and sedentary behavior between partners. Data were analyzed using coordinated multilevel modeling. RESULTS: In both studies, hourly MVPA and sedentary behavior exhibited similarly sized dyadic covariation between partners in the low-to-medium range of effects. Higher MVPA synchrony between partners was linked with higher individual weekly MVPA and higher individual weekly sedentary levels, whereas higher sedentary synchrony between partners was associated with higher individual weekly MVPA but lower individual weekly sedentary levels. MVPA and sedentary synchrony were higher in the morning and evening, more pronounced on weekends, and associated with more time spent together, longer relationship duration, and time-varying perceptions of higher partner closeness. CONCLUSIONS: This study demonstrates that MVPA and sedentary behaviors do not occur in a social vacuum. Instead, they are linked with close others such as partners. Thus, capitalizing on social partners may increase the effectiveness of individual-level physical activity interventions.

Blood pressure measurement and the prevalence of postprandial hypotension.

BACKGROUND: Postprandial hypotension (PPH) is a serious condition that has been shown to be an independent risk factor for falls, fractures and death. PURPOSE: The prevalence of this problem in older adults with a past history of falls has shown a wide variability in the literature; the present study seeks to examine how the frequency with which blood pressure is measured impacts the prevalence and severity of PPH. METHODS: Older adults were recruited sequentially from a geriatric medicine falls clinic for meal testing (n=95). All subjects (mean age 77.5±0.7 years, 61±5% female) were fasting prior to each 90 min standardized meal test. A Finometer (Finapres Medical Systems BV) was used to monitor blood pressure. Beat-by-beat systolic (SBP) measures were averaged for 0.5, 1, 2, 3, 5, 6, 9, 10, 15, 18, 30, 45 and 90 min respectively during the meal test. RESULTS: Using the original diagnostic method of checking mean blood pressure every 10 min resulted in a PPH prevalence of 42.1±5.1% in our population, with an overall range from 81.1±4.0% to 11.6±3.3% depending on the frequency of calculating SBP. The maximal observed postprandial decrease in SBP also showed a significant difference with blood pressure measurement frequency (p.

Effect of a Home-Based Exercise Program on Subsequent Falls Among Community-Dwelling High-Risk Older Adults After a Fall: A Randomized Clinical Trial.

Importance: Whether exercise reduces subsequent falls in high-risk older adults who have already experienced a fall is unknown. Objective: To assess the effect of a home-based exercise program as a fall prevention strategy in older adults who were referred to a fall prevention clinic after an index fall. Design, Setting, and Participants: A 12-month, single-blind, randomized clinical trial conducted from April 22, 2009, to June 5, 2018, among adults aged at least 70 years who had a fall within the past 12 months and were recruited from a fall prevention clinic. Interventions: Participants were randomized to receive usual care plus a home-based strength and balance retraining exercise program delivered by a physical therapist (intervention group; n = 173) or usual care, consisting of fall prevention care provided by a geriatrician (usual care group; n = 172). Both were provided for 12 months. Main Outcomes and Measures: The primary outcome was self-reported number of falls over 12 months. Adverse event data were collected in the exercise group only and consisted of falls, injuries, or muscle soreness related to the exercise intervention. Results: Among 345 randomized patients (mean age, 81.6 [SD, 6.1] years; 67% women), 296 (86%) completed the trial. During a mean follow-up of 338 (SD, 81) days, a total of 236 falls occurred among 172 participants in the exercise group vs 366 falls among 172 participants in the usual care group. Estimated incidence rates of falls per person-year were 1.4 (95% CI, 0.1-2.0) vs 2.1 (95% CI, 0.1-3.2), respectively. The absolute difference in fall incidence was 0.74 (95% CI, 0.04-1.78; P = .006) falls per person-year and the incident rate ratio was 0.64 (95% CI, 0.46-0.90; P = .009). No adverse events related to the intervention were reported. Conclusions and Relevance: Among older adults receiving care at a fall prevention clinic after a fall, a home-based strength and balance retraining exercise program significantly reduced the rate of subsequent falls compared with usual care provided by a geriatrician. These findings support the use of this home-based exercise program for secondary fall prevention but require replication in other clinical settings. Trial Registration: ClinicalTrials.gov Identifiers: NCT01029171; NCT00323596.

Safety and Tolerability of Leucine Supplementation in Elderly Men.

Leucine, a branched-chain amino acid, has been shown to stimulate muscle protein synthesis and has been suggested to play a role in the prevention of age-related muscle atrophy (sarcopenia). Although leucine supplementation may be beneficial, the efficacious dose of leucine is unknown. Before conducting studies with increased doses of leucine, the Tolerable Upper Intake Level (UL) for leucine needs to be determined. The objective of this review is to describe 2 current studies to determine the UL for leucine in young and elderly men. Initially, in young men we tested the conceptual model of determining the maximum oxidative capacity of an amino acid to be an ideal marker for identifying the UL. Leucine oxidation, measured with the use of l-[1-13C]leucine, increased with increasing leucine intakes and reached a plateau at higher intakes. Two-phase linear regression analysis identified a breakpoint of 550 mg ⋅ kg-1 ⋅ d-1 (95% CI: 454, 646 mg ⋅ kg-1 ⋅ d-1), with a simultaneous increase in blood ammonia concentrations above normal values (35 µmol/L). Recently, a similar study was conducted in elderly men (∼72 y old). A breakpoint in leucine oxidation was observed at 431 mg ⋅ kg-1 ⋅ d-1 (95% CI: 351, 511 mg ⋅ kg-1 ⋅ d-1), with blood ammonia concentrations above normal (35 µmol/L) at leucine intakes >550 mg ⋅ kg-1 ⋅ d-1 Taking the data together, the UL for leucine intake in healthy elderly men could be set at a value similar to young men, at 500 mg ⋅ kg-1 ⋅ d-1, or ∼35 g/d for an individual weighing 70 kg; or, as a cautious estimate, the leucine UL could also be considered as 351 mg ⋅ kg-1 ⋅ d-1 (the lower 95% CI), which would be ∼24.5 g/d for an elderly individual weighing 70 kg. These studies to determine the UL for leucine in humans are acute diet studies, and future studies with additional biomarkers and long-term supplementation of leucine will be necessary.

Determination of the safety of leucine supplementation in healthy elderly men.

Leucine, a branched-chain amino acid (BCAA), has been shown to stimulate muscle protein synthesis, and thus has been proposed to prevent age-related muscle atrophy (sarcopenia). Therefore, leucine supplementation may have potential benefits in elderly populations to preserve muscle mass. The tolerable upper intake level (UL) for leucine intake in young men has recently been determined to be 500 mg kg(-1) day(-1), and increases in blood ammonia concentrations were seen at intake levels above 500 mg kg(-1) day(-1); the UL for leucine in elderly is unknown. The objective of the current study was to determine the safety of leucine supplementation in healthy elderly men. Six healthy elderly men (72.2 ± 3.5 years) received graded stepwise increases in leucine intakes ranging from 50 to 750 mg kg(-1) day(-1), on eight separate study days. Plasma and urinary biochemical variables, including blood ammonia, and an oral primed-continuous protocol of L-1-(13)C-Leucine was performed. Blood ammonia concentrations above normal values (35 µmol/L) were observed at leucine intakes >550 mg kg(-1) day(-1). Leucine oxidation measured as a F(13)CO2 (rate of label tracer oxidation) increased with increasing leucine intakes and started to plateau after 450 mg kg(-1) day(-1). Two-phased linear regression analysis of the F(13)CO2 data revealed a breakpoint of 431 mg kg(-1) day(-1) (R (2) = 0.73), suggesting that the upper limit to oxidize leucine was reached at that point. Taking the data together the upper limit for leucine intake in healthy elderly could be set similar to young men at 500 mg kg(-1) day(-1) or ~35 g/day for an individual weighing 70 kg.

Activity Profile and Energy Expenditure Among Active Older Adults, British Columbia, 2011-2012.

INTRODUCTION: Time spent by young adults in moderate to vigorous activity predicts daily caloric expenditure. In contrast, caloric expenditure among older adults is best predicted by time spent in light activity. We examined highly active older adults to examine the biggest contributors to energy expenditure in this population. METHODS: Fifty-four community-dwelling men and women aged 65 years or older (mean, 71.4 y) were enrolled in this cross-sectional observational study. All were members of the Whistler Senior Ski Team, and all met current American guidelines for physical activity. Activity levels (sedentary, light, and moderate to vigorous) were recorded by accelerometers worn continuously for 7 days. Caloric expenditure was measured using accelerometry, galvanic skin response, skin temperature, and heat flux. Significant variables were entered into a stepwise multivariate linear model consisting of activity level, age, and sex. RESULTS: The average (standard deviation [SD]) daily nonlying sedentary time was 564 (92) minutes (9.4 [1.5] h) per day. The main predictors of higher caloric expenditure were time spent in moderate to vigorous activity (standardized ß = 0.42 [SE, 0.08]; P < .001) and male sex (standardized ß = 1.34 [SE, 0.16]; P < .001). A model consisting of only moderate to vigorous physical activity and sex explained 68% of the variation in caloric expenditure. An increase in moderate to vigorous physical activity by 1 minute per day was associated with an additional 16 kcal expended in physical activity. CONCLUSION: The relationship between activity intensity and caloric expenditure in athletic seniors is similar to that observed in young adults. Active older adults still spend a substantial proportion of the day engaged in sedentary behaviors.

Accelerometer-based measures of sedentary behavior and cardio-metabolic risk in active older adults.

PURPOSE: Sedentary behavior has been proposed as an independent cardio-metabolic risk factor even in adults who are physically active through recreational activity. Because little is known about the metabolic effects of sedentariness in seniors, the relationship between sedentary behavior and cardio-metabolic risk was examined in physically active older adults. METHODS: Fifty-four community dwelling men and women > 65 years of age (mean 71.5 years) were enrolled in this cross-sectional observational study. Subjects were in good health and free of known diabetes. Activity levels (sedentary, light, moderate to vigorous activity time per day) were recorded with accelerometers worn continuously for 7 days. Cardio-metabolic risk factors measured consisted of the American Heart Association diagnostic criteria for metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein, systolic blood pressure and fasting glucose) as well as low-density lipoprotein (LDL). The relationships between activity measures and cardio-metabolic risk factors were examined. Significant variables were then entered into a stepwise multivariate regression model. RESULTS: All but one subject achieved exercise levels recommended by the American College of Sports Medicine. The average proportion of time spent at a sedentary activity level each day was 72.7%. From the regression analysis, the only significant association found between cardio-metabolic risk outcomes and activity predictors was between LDL and sedentary time, with LDL detrimentally associated with average sedentary time per day (Standardized Beta Correlation Coefficient 0.302, p < 0.05). CONCLUSION: Sedentary behavior is associated with an adverse metabolic effect on LDL in seniors, even those who meet guideline recommendations for an active "fit" adult.

Physical activity correlates with arterial stiffness in community-dwelling individuals with stroke.

BACKGROUND: Physical inactivity contributes to atherosclerotic processes, which manifest as increased arterial stiffness. Arterial stiffness is associated with myocardial demand and coronary perfusion and is a risk factor for stroke and other adverse cardiac outcomes. Poststroke mobility limitations often lead to physical inactivity and sedentary behaviors. This exploratory study aimed to identify functional correlates, reflective of daily physical activity levels, with arterial stiffness in community-dwelling individuals >1 year poststroke. METHODS: Carotid-femoral pulse wave velocity (cfPWV) was measured in 35 participants (65% men; mean ± SD age 66.9 ± 6.9 years; median time poststroke 3.7 years). Multivariable regression analyses examined the relationships between cfPWV and factors associated with daily physical activity: aerobic capacity (VO2 peak), gait speed, and balance ability (Berg Balance Scale). Age and the use of antihypertensive medications, known to be associated with pulse wave velocity, were also included in the model. RESULTS: Mean cfPWV was 11.2 ± 2.4 m/s. VO2 peak and age were correlated with cfPWV (r = -0.45 [P = .006] and r = 0.46 [P = .004], respectively). In the multivariable regression analyses, age and the use of antihypertensive medication accounted for 20.4% of the variance of cfPWV, and the addition of VO2 peak explained an additional 4.5% of the variance (R2 = 0.249). CONCLUSIONS: We found that arterial stiffness is elevated in community-dwelling, ambulatory individuals with stroke relative to healthy people. Multivariable regression analysis suggests that aerobic capacity (VO2 peak) may contribute to the variance of cfPWV after accounting for the effects of age and medication use. Whether intense risk modification and augmented physical activity will improve arterial stiffness in this population remains to be determined.

Let's Enjoy an Evening on the Couch? A Daily Life Investigation of Shared Problematic Behaviors in Three Couple Studies.

Symptom-system fit theory proposes that problematic behaviors are maintained by the social system (e.g., the couple relationship) in which they occur because they help promote positive relationship functioning in the short-term. Across three daily life studies, we examined whether mixed-gender couples reported more positive relationship functioning on days in which they engaged in more shared problematic behaviors. In two studies (Study 1: 82 couples who smoke; Study 2: 117 couples who are inactive), days of more shared problematic behavior were accompanied by higher daily closeness and relationship satisfaction. A third study with 79 couples post-stroke investigating unhealthy eating failed to provide evidence for symptom-system fit. In exploratory lagged analyses, we found more support for prior-day problematic behavior being associated with next-day daily relationship functioning than vice-versa. Together, findings point to the importance of a systems perspective when studying interpersonal dynamics that might be involved in the maintenance of problematic behaviors.

Daily Rumination-Affect Associations in Dyads During the COVID-19 Pandemic.

OBJECTIVES: Negative and repetitive self-oriented thinking (rumination) is associated with lower well-being and health. The social context of rumination remains underexplored and mostly centers on marital relationships. To embrace the diversity of older adult relationships, this study includes a range of different relationships (e.g., spouses, siblings, friends, etc.) and examines the role of rumination by close others on individual well-being during the coronavirus disease 2019 pandemic. METHODS: Using daily diary data from 140 Canadian older adults (M = 72.21 years, standard deviation [SD] = 5.39, range: 63-87 years, 47% women, 71% university educated) and a close other of their choice (M = 59.95 years, SD = 16.54, range: 18-83 years, 78% women, 81% university educated), this project builds on past research examining daily life rumination dynamics from a dyadic perspective. For 10 days, both dyad members reported their daily rumination and affect quality in the evening. RESULTS: Multilevel models replicate past work showing that individual rumination was associated with higher negative affect (within-person: b = 0.27, p < .001, between-person: b = 0.57, p < .001) and lower positive affect (within-person: b = -0.18, p < .001, between-person: b = -0.29, p < .001). Importantly, we additionally observed that partner rumination was associated with higher negative affect (b = 0.03, p = .038) and lower positive affect (b = -0.04, p = .023), highlighting the social context of rumination. DISCUSSION: Findings illustrate the significance of rumination for the self and others and underline the merit of taking a dyadic perspective on what is typically viewed as an individual-level phenomenon.