What proportion of the brain structural and functional abnormalities observed among children with fetal alcohol spectrum disorder is explained by their prenatal alcohol exposure and their other prenatal and postnatal risks?

BACKGROUND: Individuals with prenatal alcohol exposure (PAE) often present with a myriad of other prenatal (e.g. exposure to tobacco and other illicit drugs, poor prenatal care) and postnatal risk factors (e.g. multiple home placements, physical/sexual abuse, low socio-economic status)-all of which are likely contributing to their adverse outcomes. METHODS: A comprehensive neuropsychological battery, coupled with magnetic resonance imaging, was administered to children with fetal alcohol spectrum disorders (FASD) in 2009. Study participants diagnosed with FASD by the University of Washington using the FASD 4-Digit Code were compared to typically-developing peers with no PAE. Data from this MRI study were used to explore the proportion of variance in brain structural and functional abnormalities explained by PAE and 14 other prenatal and postnatal risk factors. RESULTS: PAE was the dominant risk factor explaining the largest proportion of variance in regional brain size (total brain, frontal lobe, caudate, hippocampus and corpus callosum) and brain function (intellect, achievement, memory, language, executive-function, motor, adaptation, behavior-attention and mental health symptoms). Other prenatal and postnatal risk factors were 3 to 7-fold more prevalent than in the general population. Individually, each risk factor explained a statistically significant, but smaller proportion of variance in brain outcome compared to PAE. In combination, the proportion of variance explained by the presence of multiple prenatal and postnatal risks rivaled that of PAE. CONCLUSION: A better understanding of the impact other prenatal and postnatal risk factors have on the neurodevelopmental outcomes of individuals with FASD can inform more effective prevention and intervention strategies.

Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs.

BACKGROUND: Metronidazole has a substantial impact on the gut microbiome. However, the recovery of the microbiome after discontinuation of administration, and the metabolic consequences of such alterations have not been investigated to date. OBJECTIVES: To describe the impact of 14-day metronidazole administration, alone or in combination with a hydrolyzed protein diet, on fecal microbiome, metabolome, bile acids (BAs), and lactate production, and on serum metabolome in healthy dogs. ANIMALS: Twenty-four healthy pet dogs. METHODS: Prospective, nonrandomized controlled study. Dogs fed various commercial diets were divided in 3 groups: control group (no intervention, G1); group receiving hydrolyzed protein diet, followed by metronidazole administration (G2); and group receiving metronidazole only (G3). Microbiome composition was evaluated with sequencing of 16S rRNA genes and quantitative polymerase chain reaction (qPCR)-based dysbiosis index. Untargeted metabolomics analysis of fecal and serum samples was performed, followed by targeted assays for fecal BAs and lactate. RESULTS: No changes were observed in G1, or G2 during diet change. Metronidazole significantly changed microbiome composition in G2 and G3, including decreases in richness (P < .001) and in key bacteria such as Fusobacteria (q < 0.001) that did not fully resolve 4 weeks after metronidazole discontinuation. Fecal dysbiosis index was significantly increased (P < .001). Those changes were accompanied by increased fecal total lactate (P < .001), and decreased secondary BAs deoxycholic acid and lithocholic acid (P < .001). CONCLUSION AND CLINICAL IMPORTANCE: Our results indicate a minimum 4-week effect of metronidazole on fecal microbiome and metabolome, supporting a cautious approach to prescription of metronidazole in dogs.

Comparison of the 4-Digit Code, Canadian 2015, Australian 2016 and Hoyme 2016 fetal alcohol spectrum disorder diagnostic guidelines.

BACKGROUND: As clinicians strive to achieve consensus worldwide on how best to diagnose fetal alcohol spectrum disorders (FASD), the most recent FASD diagnostic systems show convergence and divergence. Applying these systems to a single clinical population illustrates the contrasts between them, but validation studies are ultimately required to identify the best system. METHODS: The 4-Digit-Code, Hoyme 2016, Canadian 2015 and Australian 2016 FASD diagnostic systems were applied to 1,392 patient records evaluated for FASD at the University of Washington. The diagnostic criteria and tools, the prevalence and concordance of diagnostic outcomes, and validity measures were compared between the systems. RESULTS: The proportion diagnosed with fetal alcohol syndrome (FAS) and FASD varied significantly (4-Digit-Code 2.1%, ≤79%; Hoyme 6.4%, 44%, Australian 1.8%, 29%; Canadian 1.8%, 16%). Eighty-two percent were diagnosed FASD by at least one system; only 11% by all four systems. Key factors contributing to discordance include: requiring high alcohol exposure; excluding growth deficiency; relaxing the facial criteria; requiring brain criteria that prevent diagnosis of infants/toddlers; and excluding moderate dysfunction from the spectrum. Primate research confirms moderate dysfunction (1-2 domains ≤-2 standard deviations) is the most prevalent outcome caused by PAE (FAS 5%, severe dysfunction 31%, moderate dysfunction 59%). Only the 4-Digit-Code replicated this diagnostic pattern. CONCLUSION: The needs of individuals with FASD are best met when diagnostic systems provide accurate, validated diagnoses across the lifespan, the full spectrum of outcome, the full continuum of alcohol exposure; and utilize diagnostic nomenclature that accurately reflects the association between outcome and alcohol exposure.

Administration of a Synbiotic Containing Enterococcus faecium Does Not Significantly Alter Fecal Microbiota Richness or Diversity in Dogs With and Without Food-Responsive Chronic Enteropathy.

Background: Canine chronic enteropathies (CE) are a group of intestinal diseases that can be categorized based on treatment response into diet- or food- responsive enteropathy (FRD), antibiotic-responsive enteropathy, steroid-responsive enteropathy, and non-responsive enteropathy. CE can often be associated with intestinal dysbiosis and thus administration of probiotic or synbiotic products may provide a useful tool for the management of some of these patients. Enterococcus faecium (EF) is a probiotic strain included in a commercially available synbiotic for small animals, however its impact on the microbial communities in dogs with FRD has not yet been evaluated. Hypothesis/Objectives: The administration of a synbiotic will lead to a significant difference of the fecal microbial composition and/or diversity in dogs with FRD, and these changes are not attributable to diet change alone. Animals/Samples: Twelve dogs with FRD fed a hydrolyzed protein diet received either a synbiotic (EF, fructooligosaccharides, gum Arabic) or placebo. Fecal samples were taken before and 6 weeks into treatment. Fecal samples were also acquired from 8 healthy dogs before and 6 weeks after being switched to the same hydrolyzed protein diet as their sole food. Methods: Bacterial DNA was extracted from fecal samples and next generation sequencing based on the 16S rRNA genes was performed. Microbial composition and diversity between groups were compared using QIIME. Results: There was a small increase in species diversity in the feces of dogs with FRD treated with synbiotics. However, there were no significant differences in microbial community composition before and after 6 weeks in either the synbiotic or placebo treated dogs with FRD or the healthy dogs. In all groups, large individual variations were observed. Conclusions: No changes in microbial composition were observed in diseased or healthy dogs with diet change alone. However, administration of a synbiotic increased bacterial richness in both groups.

Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.

Importance: The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero. Objective: To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy. Design, Setting, and Participants: A total of 1 791 520 Swedish children born between January 1, 1973, and December 31, 2014, were observed for up to 41 years using linked population-based registries. Children were excluded if they were born too late to contribute person-time, died before being at risk for the outcome, or were missing particular model data. Infection and psychiatric diagnoses were derived using codes from hospitalizations. Directed acyclic graphs were developed from a systematic literature review to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses. Statistical analysis was conducted from February 10 to October 17, 2018. Exposures: Hospitalization during pregnancy with any maternal infection, severe maternal infection, and urinary tract infection. Main Outcomes and Measures: Inpatient diagnosis of autism, depression, bipolar disorder, or psychosis among offspring. Results: A total of 1 791 520 Swedish-born children (48.6% females and 51.4% males) were observed from birth up to age 41 years, with a total of 32 125 813 person-years. Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (hazard ratio [HR], 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42). Effect estimates for autism and depression were similar following a severe maternal infection (autism: HR, 1.81; 95% CI, 1.18-2.78; depression: HR, 1.24; 95% CI, 0.88-1.73) or urinary tract infection (autism: HR, 1.89; 95% CI, 1.23-2.90; depression: HR, 1.30; 95% CI, 1.04-1.61) and were robust to moderate unknown confounding. Within the directed acyclic graph framework of assumptions, the relationship between infection and depression was vulnerable to bias from loss to follow-up, but separate data from the Swedish Death Registry demonstrated increased risk of suicide among individuals exposed to pregnancy infection. No evidence was found for increased risk of bipolar disorder or psychosis among children exposed to infection in utero. Conclusions and Relevance: These findings suggest that fetal exposure to a maternal infection while hospitalized increased the risk for autism and depression, but not bipolar or psychosis, during the child's life. These results emphasize the importance of avoiding infections during pregnancy, which may impart subtle fetal brain injuries contributing to development of autism and depression.

Transgenic overexpression of glutathione S-transferase µ-type 1 reduces hypertension and oxidative stress in the stroke-prone spontaneously hypertensive rat.

BACKGROUND: Combined congenic breeding and microarray gene expression profiling previously identified glutathione S-transferase µ-type 1 (Gstm1) as a positional and functional candidate gene for blood pressure (BP) regulation in the stroke-prone spontaneously hypertensive (SHRSP) rat. Renal Gstm1 expression in SHRSP rats is significantly reduced when compared with normotensive Wistar Kyoto (WKY) rats. As Gstm1 plays an important role in the secondary defence against oxidative stress, significantly lower expression levels may be functionally relevant in the development of hypertension. The aim of this study was to investigate the role of Gstm1 in BP regulation and oxidative stress by transgenic overexpression of the Gstm1 gene. METHOD: Two independent Gstm1 transgenic SHRSP lines were generated by microinjecting SHRSP embryos with a linear construct controlled by the EF-1α promoter encoding WKY Gstm1 cDNA [SHRSP-Tg(Gstm1)1 and SHRSP-Tg(Gstm1)2]. RESULTS: Transgenic rats exhibit significantly reduced BP and pulse pressure when compared with SHRSP [systolic: SHRSP 205.2 ±â€Š3.7 mmHg vs. SHRSP-Tg(Gstm1)1 175.5 ±â€Š1.6 mmHg and SHRSP-Tg(Gstm1)2 172 ±â€Š3.2 mmHg, P < 0.001; pulse pressure: SHRSP 58.4 ±â€Š0.73 mmHg vs. SHRSP-Tg(Gstm1)1 52.7 ±â€Š0.19 mmHg and SHRSP-Tg(Gstm1)2 40.7 ±â€Š0.53 mmHg, P < 0.001]. Total renal and aortic Gstm1 expression in transgenic animals was significantly increased compared with SHRSP [renal relative quantification (RQ): SHRSP-Tg(Gstm1)1 1.95 vs. SHRSP 1.0, P < 0.01; aorta RQ: SHRSP-Tg(Gstm1)1 2.8 vs. SHRSP 1.0, P < 0.05]. Renal lipid peroxidation (malondialdehyde: protein) and oxidized : reduced glutathione ratio levels were significantly reduced in both transgenic lines when compared with SHRSP [malondialdehyde: SHRSP 0.04 ±â€Š0.009 µmol/l vs. SHRSP-Tg(Gstm1)1 0.024 ±â€Š0.002 µmol/l and SHRSP-Tg(Gstm1)2 0.021 ±â€Š0.002 µmol/l; (oxidized : reduced glutathione ratio): SHRSP 5.19 ±â€Š2.26 µmol/l vs. SHRSP-Tg(Gstm1)1 0.17 ±â€Š0.11 µmol/l and SHRSP-Tg(Gstm1)2 0.47 ±â€Š0.22 µmol/l]. Transgenic SHRSP rats containing the WKY Gstm1 gene demonstrate significantly lower BP, reduced oxidative stress and improved levels of renal Gstm1 expression. CONCLUSION: These data support the hypothesis that reduced renal Gstm1 plays a role in the development of hypertension.

The Aftermath of Zika: Need for Long-Term Monitoring of Exposed Children.

Pregnancy infections with Zika virus are associated with a spectrum of fetal brain injuries beyond microcephaly. Nonmicrocephalic children exposed to Zika virus in utero or early life should undergo neurodevelopmental testing to identify deficits and allow for early intervention. Additionally, long-term monitoring for higher order neurocognitive deficits should be implemented.

Twin study confirms virtually identical prenatal alcohol exposures can lead to markedly different fetal alcohol spectrum disorder outcomes-fetal genetics influences fetal vulnerability.

BACKGROUND: Risk of fetal alcohol spectrum disorder (FASD) is not based solely on the timing and level of prenatal alcohol exposure (PAE). The effects of teratogens can be modified by genetic differences in fetal susceptibility and resistance. This is best illustrated in twins. OBJECTIVE: To compare the prevalence and magnitude of pairwise discordance in FASD diagnoses across monozygotic twins, dizygotic twins, full-siblings, and half-siblings sharing a common birth mother. METHODS: Data from the Fetal Alcohol Syndrome Diagnostic & Prevention Network clinical database was used. Sibling pairs were matched on age and PAE, raised together, and diagnosed by the same University of Washington interdisciplinary team using the FASD 4-Digit Code. This design sought to assess and isolate the role of genetics on fetal vulnerability/resistance to the teratogenic effects of PAE by eliminating or minimizing pairwise discordance in PAE and other prenatal/postnatal risk factors. RESULTS: As genetic relatedness between siblings decreased from 100% to 50% to 50% to 25% across the four groups (9 monozygotic, 39 dizygotic, 27 full-sibling and 9 half-sibling pairs, respectively), the prevalence of pairwise discordance in FASD diagnoses increased from 0% to 44% to 59% to 78%. Despite virtually identical PAE, 4 pairs of dizygotic twins had FASD diagnoses at opposite ends of the fetal alcohol spectrum-Partial Fetal Alcohol Syndrome versus Neurobehavioral Disorder/Alcohol-Exposed. CONCLUSION: Despite virtually identical PAE, fetuses can experience vastly different FASD outcomes. Thus, to protect all fetuses, especially the most genetically vulnerable, the only safe amount to drink is none at all.

Evaluation of the systemic micro- and macrovasculature in stable angina: A case-control study.

AIMS: The diagnosis of stable angina involves the use of probability estimates based on clinical presentation, age, gender and cardiovascular risk factors. In view of the link between the cardiac and systemic vasculature we tested whether non-invasive measures of systemic micro- and macrovascular structure and function differentiate between individuals with flow-limiting coronary artery disease (CAD) and those with normal coronary arteries (NCA). METHODS AND RESULTS: We recruited 84 patients undergoing elective coronary angiography for investigation of symptoms of stable angina. Patients were selected for either having significant CAD or NCA (n = 43/41; age, 56±7 vs 57±7 years, P = 0.309). Only microvascular endothelial function, measured using the Endo-PAT2000 device to determine reactive hyperaemia index (CAD vs. NCA; 1.9 [1.5; 2.3] vs. 2.1 [1.8; 2.4], P = 0.03) and sonographic carotid plaque score (CAD vs. NCA; 3.0 [1.5; 4.5] vs. 1.2 [0; 2.55], P<0.001) were significantly different between patients with CAD and NCA. No significant differences were detected in reflection magnitude (CAD vs. NCA; 1.7 [1.5; 1.8] % vs 1.7 [1.5; 1.9] %, P = 0.342), pulse wave velocity (CAD vs. NCA; 7.8±1.4 m/sec vs. 8.3±1.5 m/sec, P = 0.186), carotid intima-media thickness (CAD vs. NCA; 0.73±0.10 mm vs. 0.75±0.10 mm, P = 0.518) or carotid distensibility (CAD vs. NCA; 3.8±1.2 10-3/kPa vs. 3.4±0.9 10-3/kPa, P = 0.092). Also, the c-statistic of the pre-test probability based on history and traditional risk factors (c = 0.665; 95% CI, 0.540-0.789) was improved by the addition of the inverse RHI (c = 0.720; 95% CI, 0.605-0.836), carotid plaque score (c = 0.770, 95% CI, 0.659-0.881), and of both markers in combination (c = 0.801; 95% CI, 0.701-0.900). CONCLUSION: There are distinct differences in the systemic vasculature between patients with CAD and NCA that may have the potential to guide diagnostic and therapeutic decisions. Carotid artery plaque burden and microvascular function appear to be most promising in this context.

Functional implications of muscle co-contraction during gait in advanced age.

Older adults often exhibit high levels of lower extremity muscle co-contraction, which may be the cause or effect of age-related impairments in gait and associated falls. Normal gait requires intact executive function and thus can be slowed by challenging executive resources available to the neuromuscular system through the performance of a dual task. We therefore investigated associations between lower limb co-contraction and gait characteristics under normal and dual task conditions in healthy older adults (85.4±5.9years). We hypothesized that greater co-contraction is associated with slower gait speed during dual task conditions that stress executive and attentional abilities. Co-contraction was quantified during different phases of the gait cycle using surface electromyography (EMG) signals obtained from the anterior tibialis and lateral gastrocnemius while walking at preferred speed during normal and dual task conditions. Variables included the time difference to complete the Trail Making Test A and B (ΔTMT) and gait measures during normal or dual task walking. Higher co-contraction levels during the swing phase of both normal and dual task walking were associated with longer ΔTMT (normal: R2=0.25, p=0.02; dual task: R2=0.27, p=0.01). Co-contraction was associated with gait measures during dual task walking only; greater co-contraction levels during stride and stance were associated with slower gait speed (stride: R2=0.38, p=0.04; stance: R2=0.38, p=0.04), and greater co-contraction during stride was associated with longer stride time (R2=0.16, p=0.03). Our results suggest that relatively high lower limb co-contraction may explain some of the mobility impairments associated with the conduct of executive tasks in older adults.

Integrated Social- and Neurocognitive Model of Physical Activity Behavior in Older Adults with Metabolic Disease.

BACKGROUND: Despite the proven benefits of physical activity to treat and prevent metabolic diseases, such as diabetes (T2D) and metabolic syndrome (MetS), most individuals with metabolic disease do not meet physical activity (PA) recommendations. PA is a complex behavior requiring substantial motivational and cognitive resources. The purpose of this study was to examine social cognitive and neuropsychological determinants of PA behavior in older adults with T2D and MetS. The hypothesized model theorized that baseline self-regulatory strategy use and cognitive function would indirectly influence PA through self-efficacy. METHODS: Older adults with T2D or MetS (M age = 61.8 ± 6.4) completed either an 8-week physical activity intervention (n = 58) or an online metabolic health education course (n = 58) and a follow-up at 6 months. Measures included cognitive function, self-efficacy, self-regulatory strategy use, and PA. RESULTS: The data partially supported the hypothesized model (χ2 = 158.535(131), p > .05, comparative fit index = .96, root mean square error of approximation = .04, standardized root mean square residual = .06) with self-regulatory strategy use directly predicting self-efficacy (ß = .33, p < .05), which in turn predicted PA (ß = .21, p < .05). Performance on various cognitive function tasks predicted PA directly and indirectly via self-efficacy. Baseline physical activity (ß = .62, p < .01) and intervention group assignment via self-efficacy (ß = -.20, p < .05) predicted follow-up PA. The model accounted for 54.4 % of the variance in PA at month 6. CONCLUSIONS: Findings partially support the hypothesized model and indicate that select cognitive functions (i.e., working memory, inhibition, attention, and task-switching) predicted PA behavior 6 months later. Future research warrants the development of interventions targeting cognitive function, self-regulatory skill development, and self-efficacy enhancement. TRIAL REGISTRATION NUMBER: The trial was registered with the clinical trial number NCT01790724.

Urine proteomics in the diagnosis of stable angina.

BACKGROUND: We have previously described a panel of 238 urinary polypeptides specific for established severe coronary artery disease (CAD). Here we studied this polypeptide panel in patients with a wider range of CAD severity. METHODS: We recruited 60 patients who underwent elective coronary angiography for investigation of stable angina. Patients were selected for either having angiographic evidence of CAD or not (NCA) following coronary angiography (n = 30/30; age, 55 ± 6 vs. 56 ± 7 years, P = 0.539) to cover the extremes of the CAD spectrum. A further 66 patients with severe CAD (age, 64 ± 9 years) prior to surgical coronary revascularization were added for correlation studies. The Gensini score was calculated from coronary angiograms as a measure of CAD severity. Urinary proteomic analyses were performed using capillary electrophoresis coupled online to micro time-of-flight mass spectrometry. The urinary polypeptide pattern was classified using a predefined algorithm and resulting in the CAD238 score, which expresses the pattern quantitatively. RESULTS: In the whole cohort of patients with CAD (Gensini score 60 [40; 98]) we found a close correlation between Gensini scores and CAD238 (ρ = 0.465, P < 0.001). After adjustment for age (ß = 0.144; P = 0.135) the CAD238 score remained a significant predictor of the Gensini score (ß =0.418; P < 0.001). In those with less severe CAD (Gensini score 40 [25; 61]), however, we could not detect a difference in CAD238 compared to patients with NCA (-0.487 ± 0.341 vs. -0.612 ± 0.269, P = 0.119). CONCLUSIONS: In conclusion the urinary polypeptide CAD238 score is associated with CAD burden and has potential as a new cardiovascular biomarker.

White matter microstructure mediates the relationship between cardiorespiratory fitness and spatial working memory in older adults.

White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N=113 (mean age=66.61) and Experiment 2, N=154 (mean age=65.66). Using a voxel-based regression approach, we found that higher VO2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (PFDR-corrected<.05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood.

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

Impact of a brief intervention on self-regulation, self-efficacy and physical activity in older adults with type 2 diabetes.

Despite evidence of the benefits of physical activity, most individuals with type 2 diabetes do not meet physical activity recommendations. The purpose of this study was to test the efficacy of a brief intervention targeting self-efficacy and self-regulation to increase physical activity in older adults with type 2 diabetes. Older adults (Mage = 61.8 ± 6.4) with type 2 diabetes or metabolic syndrome were randomized into a titrated physical activity intervention (n = 58) or an online health education course (n = 58). The intervention included walking exercise and theory-based group workshops. Self-efficacy, self-regulation and physical activity were assessed at baseline, post-intervention, and a follow-up. Results indicated a group by time effect for self-regulation [F(2,88) = 14.021, p < .001, η (2) = .24] and self-efficacy [F(12,77) = 2.322, p < .05, η (2) = .266] with increases in the intervention group. The intervention resulted in short-term increases in physical activity (d = .76, p < .01), which were partially maintained at the 6-month follow-up (d = .35, p < .01). The intervention increased short-term physical activity but was not successful at maintaining increases in physical activity. Similar intervention effects were observed in self-efficacy and self-regulation. Future research warrants adjusting intervention strategies to increase long-term change.

Differential exercise effects on quality of life and health-related quality of life in older adults: a randomized controlled trial.

PURPOSE: Maintaining quality of life (QOL) and physical and mental health status are important outcomes throughout the aging process. Although cross-sectional studies suggest a relationship between global QOL and physical activity, it is unclear whether such a relationship exists as a function of exercise training. METHODS: We examined the effects of two exercise intervention arms on health-related quality of life (HRQOL) and global QOL. Low-active, older adults (n = 179) were randomly assigned to either a 12-month aerobic walking group or a strengthening and flexibility group. HRQOL and QOL were measured at baseline, 6, and 12 months. RESULTS: There was a significant group by time effect on QOL [F(2,176) = 3.11, p = 0.047, η (2) = 0.03]. There was also a significant overall group by time effect for HRQOL [F(4,174) = 2.46, p = 0.047, η (2) = 0.05], which was explained by the significant group by time interaction for mental health status (p = 0.041, η (2) = 0.02) favoring the walking condition. Further analyses using latent class analysis revealed three classes of individuals with differential patterns of change in QOL and HRQOL across time. These classes reflected no change, declines, and improvements in these constructs across time. CONCLUSIONS: Walking appears to enhance the mental aspect of HRQOL and global QOL when compared to a non-aerobic intervention. Additionally, the patterns of change in QOL and HRQOL were not linear over time. Our findings are in contrast to previous reports that these outcomes change a little or not at all in randomized trials.

Maintenance Effects of a DVD-Delivered Exercise Intervention on Physical Function in Older Adults.

BACKGROUND: Exercise training has been demonstrated to enhance physical function and to have a protective effect against functional limitations and disability in older adults. PURPOSE: The objective of this study was to determine whether the effects of a home-based, DVD-delivered exercise intervention on functional performance and limitations were maintained 6-month postintervention termination. METHODS: Follow-up assessments of functional performance and limitations were conducted in a sample of community-dwelling older adults (N = 237) who participated in a 6-month randomized controlled exercise trial. Participants were initially randomized to a DVD-delivered exercise intervention or an attentional control condition. The Short Physical Performance Battery, measures of flexibility and strength, and functional limitations were assessed immediately before and after the intervention and then again 6 months later. Analyses of covariance were conducted to examine changes in physical function between the two conditions at the end of the intervention to 6-month follow-up. RESULTS: There were statistically significant adjusted group differences in the Short Physical Performance Battery (η(2) = 0.03, p = .01), upper-body strength (η(2) = 0.03, p = .005), and lower-body flexibility (η(2) = 0.02, p = .05), indicating that gains brought about by the intervention were maintained 6 months later. CONCLUSIONS: A DVD-delivered exercise program specifically designed to target elements of functional fitness in older adults can produce clinically meaningful gains in physical function that are maintained beyond intervention cessation.

Physical activity levels and patterns in older adults: the influence of a DVD-based exercise program.

The use of multimedia to influence health behaviors offers unique advantages over more traditional center-based programs, however, little is known about the effectiveness of such approaches in improving physical activity levels over time. The purpose of this study was to examine the efficacy of a progressive and age-appropriate, DVD-delivered exercise program in promoting physical activity levels among older adult cohorts. Community dwelling older adults (N = 307, Mean age = 71 years) were randomized to one of two groups: a 6-month home-based DVD-delivered exercise (i.e., FlexToBa™) intervention group or a healthy aging DVD control group. Physical activity was assessed objectively using a standard 7-day accelerometer wear period and subjectively using the Godin Leisure Time Exercise Questionnaire, at baseline and follow-up. Analysis of covariances indicated a statistically significant treatment effect for subjectively [F(1,250) = 8.42, P = .004, η(2) = .03] and objectively [F(1,240) = 3.77, P = .05, η(2) = .02] measured physical activity. The older cohort (>70) in the FlexToBa condition further had significantly larger improvements in physical activity levels compared to their younger counterparts. From a public health perspective, media-delivered interventions such as the FlexToBa program might prove to be cost-effective, have a broader reach and at the same time be effective in improving physical activity levels in older adults.

Meeting physical activity guidelines in rural breast cancer survivors.

OBJECTIVES: To examine the contribution of social cognitive constructs to meeting physical activity (PA) recommendations in rural breast cancer survivors (BCS). METHODS: Rural BCS (N = 483) completed a mail-based survey. PA, fatigue, barriers and exercise self-efficacy, environment, social support, and perceived barriers to PA were assessed. PA was dichotomized into either meeting guidelines (150+minutes/week) or not. RESULTS: Our model fit the data well with less fatigue, greater efficacy, and lower barriers being associated with PA (χ²=804.532(418), p < .001, CFI=.948, RMSEA=.044, SRMR=.046). CONCLUSIONS: Fatigue, self-efficacy, and perceived barriers are key targets for future interventions designed to increase PA in rural BCS. Enhancing self-efficacy and overcoming barriers will require strategies unique and relevant to BCS living in rural settings.

Physical activity and cardiorespiratory fitness are beneficial for white matter in low-fit older adults.

Physical activity (PA) and cardiorespiratory fitness (CRF) are associated with better cognitive function in late life, but the neural correlates for these relationships are unclear. To study these correlates, we examined the association of both PA and CRF with measures of white matter (WM) integrity in 88 healthy low-fit adults (age 60-78). Using accelerometry, we objectively measured sedentary behavior, light PA, and moderate to vigorous PA (MV-PA) over a week. We showed that greater MV-PA was related to lower volume of WM lesions. The association between PA and WM microstructural integrity (measured with diffusion tensor imaging) was region-specific: light PA was related to temporal WM, while sedentary behavior was associated with lower integrity in the parahippocampal WM. Our findings highlight that engaging in PA of various intensity in parallel with avoiding sedentariness are important in maintaining WM health in older age, supporting public health recommendations that emphasize the importance of active lifestyle.