Objective: This study was carried out to examine the efficacy of a 12-week, low-intensity (1-hour/wk of therapist contact), parent-delivered intervention for toddlers at risk for autism spectrum ...disorders (ASD) aged 14 to 24 months and their families. Method: A randomized controlled trial involving 98 children and families was carried out in three different sites investigating the efficacy of a parent delivery of the Early Start Denver Model (P-ESDM), which fosters parental use of a child-centered responsive interaction style that embeds many teaching opportunities into play, compared to community treatment as usual. Assessments were completed at baseline and 12 weeks later, immediately after the end of parent coaching sessions. Results: There was no effect of group assignment on parent-child interaction characteristics or on any child outcomes. Both groups of parents improved interaction skills, and both groups of children demonstrated progress. Parents receiving P-ESDM demonstrated significantly stronger working alliances with their therapists than did the community group. Children in the community group received significantly more intervention hours than those in the P-ESDM group. For the group as a whole, both younger child age at the start of intervention and a greater number of intervention hours were positively related to the degree of improvement in children's behavior for most variables. Conclusions: Parent-implemented intervention studies for early ASD thus far have not demonstrated the large effects seen in intensive-treatment studies. Evidence that both younger age and more intervention hours positively affect developmental rates has implications for clinical practice, service delivery, and public policy. (Contains 5 tables.)
Preliminary studies suggest that neighborhood social and built environment (BE) characteristics may affect cognition in older adults. Older adults are particularly vulnerable to the neighborhood ...environment due to a decreasing range of routine travel with increasing age. We examined if multiple neighborhood BE characteristics are cross-sectionally associated with cognition in a diverse sample of older adults, and if the BE-cognition associations vary by individual-level demographics. The sample included 4539 participants from the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to examine the associations between five BE measures and four cognitive measures, and effect modification by individual-level education and race/ethnicity. In the overall sample, increasing social destination density, walking destination density, and intersection density were associated with worse overall cognition, whereas increasing proportion of land dedicated to retail was associated with better processing speed. Effect modification results suggest that the association between urban density and worse cognition may be limited to or strongest in those of non-white race/ethnicity. Although an increase in neighborhood retail destinations was associated with better cognition in the overall sample, these results suggest that certain BE characteristics in dense urban environments may have a disproportionately negative association with cognition in vulnerable populations. However, our findings must be replicated in longitudinal studies and other regional samples.
•The neighborhood built environment may affect cognition and brain aging.•Few have studied built environment and cognition associations in older age.•Three measures consistent with urban density were associated with worse cognition.•Increased neighborhood retail destinations was associated with better cognition.•Negative associations were mostly limited to those of non-white race/ethnicity.
The Canine Behavioral Assessment and Research Questionnaire (C-BARQ) is a 100-item owner-completed survey instrument used for assessing behavior and temperament of companion dogs. The shortened ...version of the C-BARQ (C-BARQ(S)) consists of 42 items of the long C-BARQ. We aimed to validate the shortened C-BARQ(S) by comparing it with the long questionnaire in the same human-dog pair. We examined data from a nationwide cohort of companion dogs enrolled in the large-scale longitudinal Dog Aging Project (DAP) study. Among 435 participating owners who completed both the long and shortened versions of the C-BARQ within 60 days of each other, agreement between individual questions of the long and shortened C-BARQ using an unweighted kappa statistic and percent agreement was examined. Associations between the two questionnaires for mean behavior and temperament domain scores and mean miscellaneous category scores were assessed using Pearson correlation coefficients. Of 435 dogs in the study, the mean (SD) age was 7.3 (4.3) years and 216 (50%) were female. Kappa values between the long and shortened C-BARQ for individual questions within the 14 behavior and temperament domains and a miscellaneous category ranged from fair to moderate (0.23 to 0.40 for 21 items and 0.41 to 0.58 for 26 items, respectively). Pearson correlation coefficients above 0.60 between both questionnaires for 12 of the 14 mean behavior and temperament domain scores and a category of miscellaneous items were observed. Kappa values for individual questions between the long and shortened C-BARQ ranged from fair to moderate and correlations between mean domain scores ranged from moderate to strong.
Metabolic imaging of the relative amounts of reduced NADH and FAD and the microenvironment of these metabolic electron carriers can be used to noninvasively monitor changes in metabolism, which is ...one of the hallmarks of carcinogenesis. This study combines cellular redox ratio, NADH and FAD lifetime, and subcellular morphology imaging in three dimensions to identify intrinsic sources of metabolic and structural contrast in vivo at the earliest stages of cancer development. There was a significant (P < 0.05) increase in the nuclear to cytoplasmic ratio (NCR) with depth within the epithelium in normal tissues; however, there was no significant change in NCR with depth in precancerous tissues. The redox ratio significantly decreased in the less differentiated basal epithelial cells compared with the more mature cells in the superficial layer of the normal stratified squamous epithelium, indicating an increase in metabolic activity in cells with increased NCR. However, the redox ratio was not significantly different between the superficial and basal cells in precancerous tissues. A significant decrease was observed in the contribution and lifetime of protein-bound NADH (averaged over the entire epithelium) in both low- and high-grade epithelial precancers compared with normal epithelial tissues. In addition, a significant increase in the protein-bound FAD lifetime and a decrease in the contribution of protein-bound FAD are observed in high-grade precancers only. Increased intracellular variability in the redox ratio, NADH, and FAD fluorescence lifetimes were observed in precancerous cells compared with normal cells.
Depression is an important precursor to dementia, but less is known about the role dementia plays in altering the course of depression. We examined whether depression prevalence, incidence, and ...severity are higher in those with dementia versus those with mild cognitive impairment (MCI), or normal cognition.
Prospective cohort study using the longitudinal Uniform Data Set of the National Alzheimer's Coordinating Center (2005-2013).
34 Alzheimer Disease research centers.
27,776 subjects with dementia, MCI, or normal cognition.
Depression status was determined by a clinical diagnosis of depression within the prior 2 years and by a Geriatric Depression Scale-Short Form score >5.
Rates of depression were significantly higher in subjects with MCI and dementia compared with those with normal cognition at index visit. Controlling for demographics and common chronic conditions, logistic regression analysis revealed elevated depression in those with MCI (OR: 2.40 95% CI: 2.25, 2.56) or dementia (OR: 2.64 95% CI: 2.43, 2.86) relative to those with normal cognition. In the subjects without depression at the index visit (N = 18,842), those with MCI and dementia had higher probabilities of depression diagnosis 2 years post index visit than those with normal cognition: MCI = 21.7%, dementia = 24.7%, normal cognition = 10.5%.
MCI and dementia were associated with significantly higher rates of depression in concurrent as well as prospective analyses. These findings suggest that efforts to effectively engage and treat older adults with dementia will need also to address co-occurring depression.
Canine cognitive dysfunction (CCD) is a neurodegenerative disease in aging dogs. It has been described previously in relatively small cohorts of dogs using multiple different rating scales. This ...study aimed to use a minimally modified CCD rating scale developed by previous researchers to describe the prevalence of CCD more thoroughly in a large, nationwide cohort of companion dogs participating in the Dog Aging Project (DAP) (n = 15,019). Associations between various canine characteristics, predicted lifespan quartiles, and CCD were examined using univariable and multivariable logistic regression models and receiver operating curve (ROC) analysis. When controlling for all other characteristics, the odds of CCD increased 52% with each additional year of age. Among dogs of the same age, health status, breed type, and sterilization status, odds of CCD were 6.47 times higher in dogs who were not active compared to those who were very active. When controlling for age, breed type, activity level, and other comorbidities, dogs with a history of neurological, eye, or ear disorders had higher odds of CCD. Lifespan quartile analysis showed excellent discriminating ability between CCD positive and negative dogs. Weight-based lifespan quartile estimation could therefore serve as a tool to inform CCD screening by veterinarians.
Background Substantial evidence supports the effectiveness of peer educator programs for diabetes management in low- and middle-income countries. However, little is known about peer educators' impact ...relative to other treatment components such as medication and physician consultation. In Cambodia, the non-governmental organization MoPoTsyo organizes four services for people with diabetes: self-management training through peer educator visits, lab tests, physician consultations, and low-cost medicines. Our aims were to 1) quantify MoPoTsyo participant utilization of each program service and 2) define the relationship between each program service and glycemic control. Methods We conducted a retrospective cohort study among 4,210 MoPoTsyo participants, using data collected by MoPoTsyo from 2006-2016. Independent variables assessed were medication adherence, number of peer educator visits, number of physician consultations, and number of lab tests. A multiple logistic regression model was used to evaluate the association between these disease management services and glycemic control-fasting plasma glucose less than or equal to130 mg/dl or post-prandial glucose less than or equal to180 mg/dl-based on most recent glucose level. The model was adjusted for baseline demographic and disease characteristics. Findings Participants with 12 or more peer educator visits per year had a 35% higher odds of glycemic control relative to participants with 4 or fewer visits (odds ratio 1.35, 95% CI: 1.08-1.69; p = 0.009), after adjustment for utilization of other treatment components (medication adherence, number of physician visits, number of lab tests), follow-up time, and demographic and disease characteristics. Better adherence to medications and a greater number of lab tests per year were also associated with a higher odds of glycemic control after adjustment. Number of physician consultations was not associated with glycemic control after adjustment. Conclusions This study demonstrates a positive association between peer educator utilization and glycemic control incremental to other elements of diabetes management. These results suggest that peer educators may be a valuable addition to comprehensive diabetes management programs in low- and middle-income countries even when other health care services are accessible. The associations identified in this research warrant further prospective studies to explore the causal impact of peer educators on glycemic control relative to other disease management components.
Air pollution might affect atherosclerosis through DNA methylation changes in cells crucial to atherosclerosis, such as monocytes. We conducted an epigenome-wide study of DNA methylation in ...CD14+ monocytes and long-term ambient air pollution exposure in adults participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We also assessed the association between differentially methylated signals and cis-gene expression. Using spatiotemporal models, one-year average concentrations of outdoor fine particulate matter (PM
2.5
) and oxides of nitrogen (NO
X
) were estimated at participants' homes. We assessed DNA methylation and gene expression using Illumina 450k and HumanHT-12 v4 Expression BeadChips, respectively (n = 1,207). We used bump hunting and site-specific approaches to identify differentially methylated signals (false discovery rate of 0.05) and used linear models to assess associations between differentially methylated signals and cis-gene expression. Four differentially methylated regions (DMRs) located on chromosomes 5, 6, 7, and 16 (within or near SDHAP3, ZFP57, HOXA5, and PRM1, respectively) were associated with PM
2.5
. The DMRs on chromosomes 5 and 6 also associated with NO
X
. The DMR on chromosome 5 had the smallest p-value for both PM
2.5
(p = 1.4×10
−6
) and NO
X
(p = 7.7×10
−6
). Three differentially methylated CpGs were identified for PM
2.5
, and cg05926640 (near TOMM20) had the smallest p-value (p = 5.6×10
−8
). NO
X
significantly associated with cg11756214 within ZNF347 (p = 5.6×10
−8
). Several differentially methylated signals were also associated with cis-gene expression. The DMR located on chromosome 7 was associated with the expression of HOXA5, HOXA9, and HOXA10. The DMRs located on chromosomes 5 and 16 were associated with expression of MRPL36 and DEXI, respectively. The CpG cg05926640 was associated with expression of ARID4B, IRF2BP2, and TOMM20. We identified differential DNA methylation in monocytes associated with long-term air pollution exposure. Methylation signals associated with gene expression might help explain how air pollution contributes to cardiovascular disease.
BackgroundPrevious studies have demonstrated an association between gait speed and cognitive function. However, the relationship between balance and cognition remains less well explored. This study ...examined the cross-sectional and longitudinal relationship of balance and cognitive decline in older adults.
MethodsA cohort of 4,811 adults, aged ≥65 years, participating in the Cardiovascular Health Study was followed for 6 years. Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST) were used to measure cognition. Tandem balance measures were used to evaluate balance. Regression models were adjusted for demographics, behavioural and disease factors.
ResultsWorse balance was independently associated with worse cognition in cross-sectional analysis. Longitudinally, participants aged ≥76 years with poorer balance had a faster rate of decline after adjustment for co-variates: −0.97 points faster decline in 3MSE per year (95% confidence interval (CI): −1.32, −0.63) compared to the participants with good balance. There was no association of balance and change in 3MSE among adults aged <76 years (P value for balance and age interaction < 0.0001). DSST scores reflected −0.21 (95% CI: −0.37, −0.05) points greater decline when adjusted for co-variates. In Cox proportional hazard models, participants with worse balance had a higher risk of being cognitively impaired over the 6 years of follow-up visits (adjusted HR:1.72, 95% CI: 1.30, 2.29).
ConclusionsFuture studies should evaluate standing balance as a potential screening technique to identify individuals at risk of cognitive decline. Furthermore, a better understanding of the pathophysiological link between balance and cognition may inform strategies to prevent cognitive decline.
To evaluate the association of salt consumption with blood pressure in Viet Nam, a developing country with a high level of salt consumption.
Analysis of a nationally representative sample of ...Vietnamese adults 25-65 years of age who were surveyed using the World Health Organization STEPwise approach to Surveillance protocol. Participants who reported acute illness, pregnancy, or current use of antihypertensive medications were excluded. Daily salt consumption was estimated from fasting mid-morning spot urine samples. Associations of salt consumption with systolic blood pressure and prevalent hypertension were assessed using adjusted linear and generalized linear models. Interaction terms were tested to assess differences by age, smoking, alcohol consumption, and rural/urban status.
The analysis included 2,333 participants (mean age: 37 years, 46% male, 33% urban). The average estimated salt consumption was 10g/day. No associations of salt consumption with blood pressure or prevalent hypertension were observed at a national scale in men or women. The associations did not differ in subgroups defined by age, smoking, or alcohol consumption; however, associations differed between urban and rural participants (p-value for interaction of urban/rural status with salt consumption, p = 0.02), suggesting that higher salt consumption may be associated with higher systolic blood pressure in urban residents but lower systolic blood pressure in rural residents.
Although there was no evidence of an association at a national level, associations of salt consumption with blood pressure differed between urban and rural residents in Viet Nam. The reasons for this differential association are not clear, and given the large rate of rural to urban migration experienced in Viet Nam, this topic warrants further investigation.
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