Kenneth M. Madden

Short-Term Aerobic Exercise Reduces Arterial Stiffness in Older Adults With Type 2 Diabetes, Hypertension, and Hypercholesterolemia

OBJECTIVE The relationship between increased arterial stiffness and cardiovascular mortality is well established in type 2 diabetes. We examined whether aerobic exercise could reduce arterial stiffness in older adults with type 2 diabetes complicated by comorbid hypertension and hyperlipidemia. RESEARCH DESIGN AND METHODS A total of 36 older adults (mean age 71.4 ± 0.7 years) with diet-controlled or oral hypoglycemic–controlled type 2 diabetes, hypertension, and hypercholesterolemia were recruited. Subjects were randomly assigned to one of two groups: an aerobic group (3 months vigorous aerobic exercise) and a nonaerobic group (no aerobic exercise). Exercise sessions were supervised by a certified exercise trainer three times per week, and a combination of cycle ergometers and treadmills was used. Arterial stiffness was measured using the Complior device. RESULTS When the two groups were compared, aerobic training resulted in a decrease in measures of both radial (−20.7 ± 6.3 vs. +8.5 ± 6.6%, P = 0.005) and femoral (−13.9 ± 6.7 vs. +4.4 ± 3.3%, P = 0.015) pulse-wave velocity despite the fact that aerobic fitness as assessed by Vo2max did not demonstrate an improvement with training (P = 0.026). CONCLUSIONS Our findings indicate that a relatively short aerobic exercise intervention in older adults can reduce multifactorial arterial stiffness (type 2 diabetes, aging, hypertension, and hypercholesterolemia).

Genetic Variation in Healthy Oldest-Old

Individuals who live to 85 and beyond without developing major age-related diseases may achieve this, in part, by lacking disease susceptibility factors, or by possessing resistance factors that enhance their ability to avoid disease and prolong lifespan. Healthy aging is a complex phenotype likely to be affected by both genetic and environmental factors. We sequenced 24 candidate healthy aging genes in DNA samples from 47 healthy individuals aged eighty-five years or older (the ‘oldest-old’), to characterize genetic variation that is present in this exceptional group. These healthy seniors were never diagnosed with cancer, cardiovascular disease, pulmonary disease, diabetes, or Alzheimer disease. We re-sequenced all exons, intron-exon boundaries and selected conserved non-coding sequences of candidate genes involved in aging-related processes, including dietary restriction (PPARG, PPARGC1A, SIRT1, SIRT3, UCP2, UCP3), metabolism (IGF1R, APOB, SCD), autophagy (BECN1, FRAP1), stem cell activation (NOTCH1, DLL1), tumor suppression (TP53, CDKN2A, ING1), DNA methylation (TRDMT1, DNMT3A, DNMT3B) Progeria syndromes (LMNA, ZMPSTE24, KL) and stress response (CRYAB, HSPB2). We detected 935 variants, including 848 single nucleotide polymorphisms (SNPs) and 87 insertion or deletions; 41% (385) were not recorded in dbSNP. This study is the first to present a comprehensive analysis of genetic variation in aging-related candidate genes in healthy oldest-old. These variants and especially our novel polymorphisms are valuable resources to test for genetic association in models of disease susceptibility or resistance. In addition, we propose an innovative tagSNP selection strategy that combines variants identified through gene re-sequencing- and HapMap-derived SNPs.

Aerobic training restores arterial baroreflex sensitivity in older adults with type 2 diabetes, hypertension, and hypercholesterolemia.

Objective: Lowered baroreflex sensitivity (BRS) predicts mortality and occurs with increasing age and diabetes. We examined whether aerobic exercise could restore arterial BRS in adults at high cardiovascular risk (diabetes, geriatric age group, hypercholesterolemia, and hypertension). Design: Randomized, controlled, single-blind study. Setting: VITALiTY (Vancouver Initiative to Add Life to Years) Research Laboratory. Participants: Thirty-nine older adults (mean age, 71.5 ± 0.7 years) with diet-controlled or oral hypoglycemic-controlled type 2 diabetes, hypertension, and hypercholesterolemia. Interventions: Subjects were recruited to each of 2 groups: an aerobic group (3 months of vigorous aerobic exercise as defined by 80% to 85% of maximal heart rate), and a nonaerobic (no aerobic exercise) group. Exercise sessions were supervised by a certified exercise trainer 3 times per week. Main Outcome Measures: Baroreflex function was assessed using the spontaneous baroreflex method. Main outcome measures included BRS, BRSup, BRSdown, and &OV0312;o2max. Results: The aerobic group demonstrated an increase in BRS that was not demonstrated in the nonaerobic group (+60.9 ± 23.5 vs +2.2 ± 7.9%; P = 0.010). Conclusions: Our findings indicate that a relatively short aerobic exercise intervention can reverse functional impairments of the arterial baroreflex function in older adults at high cardiovascular risk.

Exercise‐induced changes in cardiovascular function after stroke: a randomized controlled trial

Background and aims Cardiovascular co-morbidities are prevalent after stroke, with heart disease, hypertension and impaired glucose tolerance present in the majority of cases. Exercise has the potential to mediate cardiovascular risk factors commonly present in people with stroke. This single-blinded randomized controlled trial compared the effects of high versus low intensity exercise on fitness, cardiovascular risk factors, and cardiac function after stroke. Methods Fifty participants (age 50–80 y, >1 y post-stroke) were randomized to a high-intensity Aerobic Exercise (AE) or low-intensity non-aerobic Balance/Flexibility (BF) program (6 months, 3 60-min sessions/week). Outcomes assessed by VO2peak (primary outcome), arterial stiffness, ambulatory capacity, hemodynamics and cardiac function using echocardiography, and lipid, glucose and homocysteine levels. Assessors were blinded to group allocation. Results Twenty-three (92%) of 25 AE group participants (withdrawals unrelated to the intervention) and all BF group participants completed the program. One BF group participant experienced 2 non-injurious falls during class. No other adverse events occurred. There were no changes in VO2peak in either group (AE 16·9 ±7 to 17·4 ± 7 ml•kg−1•min−1 vs. BF 16·9 ±6 to 16·6 ± 5 ml•kg−1•min−1, P = 0·45), but AE group demonstrated greater improvement in right atrial emptying fraction (AE 30 ± 22 to 37 ± 22% vs. BF 35 ± 20 to 31 ± 20%, P = 0·04). Both groups demonstrated improvements in lipid profiles, glucose and homocysteine levels, and ambulatory capacity (P < 0·04). Conclusions This was the first study to examine the effects of aerobic exercise after stroke on cardiovascular hemodynamics. High-intensity exercise improved right-sided function and early myocardial relaxation. Low-intensity exercise may also benefit plasma lipid, glucose and inflammatory markers, and ambulatory capacity. This study is an important step towards understanding mechanisms by which exercise may reduce cardiovascular risk and function.

Aerobic training-induced improvements in arterial stiffness are not sustained in older adults with multiple cardiovascular risk factors

There is a well-established relationship between increased arterial stiffness and cardiovascular mortality. We examined whether a long-term aerobic exercise intervention (6 months) would increase arterial compliance in older adults with hypertension complicated by Type 2 diabetes (T2DM) and hyperlipidemia. A total of 52 older adults (mean age 69.3±0.6 years, 30 males and 22 females) with diet/oral hypoglycemic-controlled T2DM, hypertension and hypercholesterolemia were recruited. Subjects were randomly assigned to one of two groups: an aerobic group (6 months vigorous aerobic exercise, AT group) and a non-aerobic group (6 months of no aerobic exercise, NA group). Arterial stiffness was measured as pulse-wave velocity (PWV) using the Complior device. Aerobic training decreased arterial stiffness as measured by both radial (P=0.001, 2-way analysis of variance with repeated measures) and femoral (P=0.002) PWV. This was due to a decrease in arterial stiffness in the AT group after 3 months of training, which was not maintained after 6-month training for either radial (P=0.707) or femoral (P=0.680) PWV. Our findings indicate that in older adults with multiple cardiovascular risk factors, short-term improvements in arterial stiffness became attenuated over the long term.

Evidence for the benefit of exercise therapy in patients with type 2 diabetes

Exercise interventions are recommended in most guidelines for the treatment of type 2 diabetes. Although most guidelines suggest a combination of both aerobic and resistance training, the exact benefits of these interventions remain unclear. Although either modality alone or in combination seems to have an identical impact on glycated hemoglobin levels, resistance training and aerobic training have independent effects on other parameters of cardio-metabolic risk. This review examines the current evidence for aerobic and resistance training on glycemic control, lipid profile, body composition, vascular health, and mental health in patients with type 2 diabetes. The uncertainties surrounding exercise modality, volume and intensity are also addressed.

Not just another walking program: Everyday Activity Supports You (EASY) model—a randomized pilot study for a parallel randomized controlled trial

BackgroundMaintaining physical activity is an important goal with positive health benefits, yet many people spend most of their day sitting. Our Everyday Activity Supports You (EASY) model aims to encourage movement through daily activities and utilitarian walking. The primary objective of this phase was to test study feasibility (recruitment and retention rates) for the EASY model.MethodsThis 6-month study took place in Vancouver, Canada, from May to December 2013, with data analyses in February 2014. Participants were healthy, inactive, community-dwelling women aged 55–70 years. We recruited through advertisements in local community newspapers and randomized participants using a remote web service. The model included the following: group-based education and social support, individualized physical activity prescription (called Activity 4-1-1), and use of a Fitbit activity monitor. The control group received health-related information only. The main outcome measures were descriptions of study feasibility (recruitment and retention rates). We also collected information on activity patterns (ActiGraph GT3X+ accelerometers) and health-related outcomes such as body composition (height and weight using standard techniques), blood pressure (automatic blood pressure monitor), and psychosocial variables (questionnaires).ResultsWe advertised in local community newspapers to recruit participants. Over 3 weeks, 82 participants telephoned; following screening, 68% (56/82) met the inclusion criteria and 45% (25/56) were randomized by remote web-based allocation. This included 13 participants in the intervention group and 12 participants in the control group (education). At 6 months, 12/13 (92%) intervention and 8/12 (67%) control participants completed the final assessment. Controlling for baseline values, the intervention group had an average of 2,080 [95% confidence intervals (CIs) 704, 4,918] more steps/day at 6 months compared with the control group. There was an average between group difference in weight loss of −4.3 [95% CI −6.22, −2.40] kg and reduction in diastolic blood pressure of −8.54 [95% CI −16.89, −0.198] mmHg, in favor of EASY.ConclusionsThe EASY pilot study was feasible to deliver; there was an increase in physical activity and reduction in weight and blood pressure for intervention participants at 6 months.Trial registrationClinicalTrials.gov identifier: NCT01842061Background Maintaining physical activity is an important goal with positive health benefits, yet many people spend most of their day sitting. Our Everyday Activity Supports You (EASY) model aims to encourage movement through daily activities and utilitarian walking. The primary objective of this phase was to test study feasibility (recruitment and retention rates) for the EASY model. Methods This 6-month study took place in Vancouver, Canada, from May to December 2013, with data analyses in February 2014. Participants were healthy, inactive, community-dwelling women aged 55–70 years. We recruited through advertisements in local community newspapers and randomized participants using a remote web service. The model included the following: group-based education and social support, individualized physical activity prescription (called Activity 4-1-1), and use of a Fitbit activity monitor. The control group received health-related information only. The main outcome measures were descriptions of study feasibility (recruitment and retention rates). We also collected information on activity patterns (ActiGraph GT3X+ accelerometers) and health-related outcomes such as body composition (height and weight using standard techniques), blood pressure (automatic blood pressure monitor), and psychosocial variables (questionnaires). Results We advertised in local community newspapers to recruit participants. Over 3 weeks, 82 participants telephoned; following screening, 68% (56/82) met the inclusion criteria and 45% (25/56) were randomized by remote web-based allocation. This included 13 participants in the intervention group and 12 participants in the control group (education). At 6 months, 12/13 (92%) intervention and 8/12 (67%) control participants completed the final assessment. Controlling for baseline values, the intervention group had an average of 2,080 [95% confidence intervals (CIs) 704, 4,918] more steps/day at 6 months compared with the control group. There was an average between group difference in weight loss of −4.3 [95% CI −6.22, −2.40] kg and reduction in diastolic blood pressure of −8.54 [95% CI −16.89, −0.198] mmHg, in favor of EASY. Conclusions The EASY pilot study was feasible to deliver; there was an increase in physical activity and reduction in weight and blood pressure for intervention participants at 6 months. Trial registration ClinicalTrials.gov identifier: NCT01842061 Electronic supplementary material The online version of this article (doi:10.1186/2055-5784-1-4) contains supplementary material, which is available to authorized users.

Sedentary behavior and sleep efficiency in active community-dwelling older adults

Objectives Previous studies have demonstrated that aerobic exercise interventions have a positive impact on sleep efficiency in older adults. However, little work has been done on the impact of sedentary behavior (sitting, watching television, etc.) on sleep efficiency. Methods 54 Community-dwelling men and women >65 years of age living in Whistler, British Columbia (mean 71.5 years) were enrolled in this cross-sectional observational study. Measures of sleep efficiency as well as average waking sedentary (ST), light (LT), and moderate (MT) activity were recorded with Sensewear accelerometers worn continuously for 7 days. Results From the univariate regression analysis, there was no association between sleep efficiency and the predictors LT and MT. There was a small negative association between ST and sleep efficiency that remained significant in our multivariate regression model containing alcohol consumption, age and gender as covariates. (standardized β correlation coefficient −0.322, p=0.019). Although significant, this effect was small (an increase in sedentary time of 3 hours per day was associated with an approximately 5% reduction in sleep efficiency). Conclusions This study found a small significant association between the time spent sedentary and sleep efficiency, despite high levels of activity in this older adult group.

A Scoping Review of Frailty and Acute Care in Middle-Aged and Older Individuals with Recommendations for Future Research

There is general agreement that frailty is a state of heightened vulnerability to stressors arising from impairments in multiple systems leading to declines in homeostatic reserve and resiliency, but unresolved issues persist about its detection, underlying pathophysiology, and relationship with aging, disability, and multimorbidity. A particularly challenging area is the relationship between frailty and hospitalization. Based on the deliberations of a 2014 Canadian expert consultation meeting and a scoping review of the relevant literature between 2005 and 2015, this discussion paper presents a review of the current state of knowledge on frailty in the acute care setting, including its prevalence and ability to both predict the occurrence and outcomes of hospitalization. The examination of the available evidence highlighted a number of specific clinical and research topics requiring additional study. We conclude with a series of consensus recommendations regarding future research priorities in this important area.

Elevated body mass index and maintenance of cognitive function in late life: exploring underlying neural mechanisms

Background: Obesity is associated with vascular risk factors that in turn, may increase dementia risk. However, higher body mass index (BMI) in late life may be neuroprotective. The possible neural mechanisms underlying the benefit of higher BMI on cognition in older adults are largely unknown. Thus, we used functional connectivity magnetic resonance imaging (fcMRI) to examine: (1) the relationship between BMI and functional brain connectivity; and (2) the mediating role of functional brain connectivity in the association between baseline BMI and change in cognitive function over a 12-month period. Methods:We conducted a 12-month, prospective study among 66 community-dwelling older adults, aged 70 to 80 years, who were categorized as: normal weight (BMI from 18.50 to 24.99); overweight (BMI from 25.00 to 29.99); and obese (BMI ≥ 30.00). At baseline, participants performed a finger-tapping task during fMRI scanning. Relevant neural networks were initially identified through independent component analysis (ICA) and subsequently examined through seed-based functional connectivity analysis. At baseline and 12-months, we measured three executive cognitive processes: (1) response inhibition; (2) set shifting; and (3) working memory. Results:Obese individuals showed lower task-related functional connectivity during finger tapping in the default mode network (DMN) compared with their healthy weight counterparts (p < 0.01). Lower task-related functional connectivity in the DMN at baseline was independently associated with better working memory performance at 12-months (p = 0.02). Finally, DMN functional connectivity during finger tapping significantly mediated the relationship between baseline BMI and working memory at 12-months (indirect effect: −0.155, 95% confidence interval [−0.313, −0.053]). Conclusions:These findings suggest that functional connectivity of the DMN may be an underlying mechanism by which higher BMI confers protective effects to cognition in late life.