Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: experience at a single, large care center

Aim: To assess outcomes among patients with Duchenne muscular dystrophy receiving deflazacort or prednisone in real-world practice. Methods: Clinical data for 435 boys with Duchenne muscular dystrophy from Cincinnati Children\u27s Hospital Medical Center were studied retrospectively using time-to-event and regression analyses. Results: Median ages at loss of ambulation were 15.6 and 13.5 years among deflazacort- and prednisone-initiated patients, respectively. Deflazacort was also associated with a lower risk of scoliosis and better ambulatory function, greater % lean body mass, shorter stature and lower weight, after adjusting for age and steroid duration. No differences were observed in whole body bone mineral density or left ventricular ejection fraction. Conclusion: This single center study adds to the real-world evidence associating deflazacort with improved clinical outcomes

Dementia and dependence: Do modifiable risk factors delay disability?

OBJECTIVE: To identify modifying factors that preserve functional independence among individuals at high dementia risk. METHODS: Health and Retirement Study participants aged 65 years or older without baseline activities of daily living (ADL) limitations (n = 4,922) were interviewed biennially for up to 12 years. Dementia probability, estimated from direct and proxy cognitive assessments, was categorized as low (i.e., normal cognitive function), mild, moderate, or high risk (i.e., very impaired) and used to predict incident ADL limitations (censoring after limitation onset). We assessed multiplicative and additive interactions of dementia category with modifiers (previously self-reported physical activity, smoking, alcohol consumption, depression, and income) in predicting incident limitations. RESULTS: Smoking, not drinking, and income predicted incident ADL limitations and had larger absolute effects on ADL onset among individuals with high dementia probability than among cognitively normal individuals. Smoking increased the 2-year risk of ADL limitations onset from 9.9% to 14.9% among the lowest dementia probability category and from 32.6% to 42.7% among the highest dementia probability category. Not drinking increased the 2-year risk of ADL limitations onset by 2.1 percentage points among the lowest dementia probability category and 13.2 percentage points among the highest dementia probability category. Low income increased the 2-year risk of ADL limitations onset by 0.4% among the lowest dementia probability category and 12.9% among the highest dementia probability category. CONCLUSIONS: Smoking, not drinking, and low income predict incident dependence even in the context of cognitive impairment. Regardless of cognitive status, reducing these risk factors may improve functional outcomes and delay institutionalization

Initiation of antidepressant medication and risk of incident stroke: using the Adult Changes in Thought cohort to address time-varying confounding

Purpose Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and incident stroke. Methods For 2302 Adult Changes in Thought cohort participants with no stroke at study entry, we characterized antidepressant use from pharmacy records, biennial depressive symptoms with a 10-item Centers for Epidemiologic Study–Depression scale, and incident strokes from ICD codes. We used discrete-time survival models with inverse probability weighting to compare stroke risk associated with filling antidepressant prescriptions and by medication category: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors, or other. Results Over an average 8.4-year follow-up, 441 incident strokes occurred. Filling antidepressant medications 3+ times versus 0–2 times predicted 35% increased odds of stroke (OR = 1.35; 95% CI: 0.98, 1.66). Use of TCAs was associated with stroke onset (OR per 10 fills = 1.28; CI: 1.04, 1.57), but use of selective serotonin reuptake inhibitors (OR = 0.98; CI: 0.80, 1.20) or other antidepressants (OR = 0.99; CI: 0.67, 1.45) was not. Conclusions Although patients who received antidepressant medication were at higher risk of stroke, this association appeared specific to TCA prescriptions

Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality

Introduction: We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality. Methods: We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years. Results: Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00–1.10, P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41–1.00, P = .05). Discussion Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence

Freshwater invertebrate responses to fine sediment stress: a multi-continent perspective

Excessive fine sediment (particles <2 mm) deposition in freshwater systems is a pervasive stressor worldwide. However, understanding of ecological response to excess fine sediment in river systems at the global scale is limited. Here, we aim to address whether there is a consistent response to increasing levels of deposited fine sediment by freshwater invertebrates across multiple geographic regions (Australia, Brazil, New Zealand, and the UK). Results indicate ecological responses are not globally consistent and are instead dependent on both the region and the facet of invertebrate diversity considered, i.e., taxonomic or functional trait structure. Invertebrate communities of Australia were most sensitive to deposited fine sediment, with the greatest rate of change in communities occurring when fine sediment cover was low (below 25% of the reach). Communities in the UK displayed greater tolerance with most compositional change occurring between 30-60% cover. In both New Zealand and Brazil, which included the most heavily sedimented sampled streams, the communities were more tolerant or demonstrated ambiguous responses, likely due to historic environmental filtering of invertebrate communities. We conclude that ecological responses to fine sediment are not generalisable globally and are dependent on landscape filters with regional context and historic land management playing important roles

Predictors of Dementia and Memory Decline: Lifecourse Socioeconomic Status and Diabetes

This dissertation examines the relationship between both lifecourse socioeconomic status and diabetes and memory decline and dementia using data from the Health and Retirement Study. Chapter 1 examines associations between lifecourse measures of socioeconomic status (SES) and late life memory function and decline. Memory function was modeled longitudinally from 2002-2012 and decline was modeled for the same years via growth curves. SES measures included childhood SES, high school and college education, as well as late life household income. Of our SES measures, education was the strongest predictor of level of memory function, whereas rate of decline was driven by late life income, suggesting that late life interventions focused on SES or its downstream consequences – like health behaviors – may have the potential to slow cognitive decline. Chapter 2 assesses socioeconomic status (SES) at three points in the lifecourse in order to evaluate alternative lifecourse models with respect to the association between SES and risk of dementia. We used generalized estimating equations with a logit link to model dementia probability from 2002-2012. SES measures included childhood SES, high school education, and late life household income. We found that high school completion was the strongest predictor of decreased dementia risk, consistent with either of two lifecourse models: a sensitive period in early adulthood and/or cumulative risk. Chapter 3 explores how type 2 diabetes (T2D) and blood glucose levels relate to cognitive decline, which is important for understanding the mechanisms driving higher dementia rates among individuals with T2D. Memory decline was modeled via generalized estimating equations using linear growth curves with diabetes, HbA1c, and covariates as predictors. Diabetes and higher levels of HbA1c both predicted faster memory decline after controlling for an extensive battery of potential social confounders in a large, U.S. dataset. Our results add support for a causal pathway from diabetes to risk of dementia. Blood glucose concentration may partially explain the association between diabetes and both dementia and cognitive decline, although precise biological mechanisms are still unknown

Contribution of Socioeconomic Status at 3 Life-Course Periods to Late-Life Memory Function and Decline: Early and Late Predictors of Dementia Risk.

Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998-2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (β = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, β = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline

Do Physical Activity, Smoking, Drinking, or Depression Modify Transitions from Cognitive Impairment to Functional Disability?

BackgroundIndividual-level modifiers can delay onset of limitations in basic activities of daily living (ADLs) among cognitively impaired individuals. We assessed whether these modifiers also delayed onset of limitations in instrumental ADLs (IADLs) among individuals at elevated dementia risk.ObjectivesTo determine whether modifiable individual-level factors delay incident IADL limitations among adults stratified by dementia risk.MethodsHealth and Retirement Study participants aged 65+ without activity limitations in 1998 or 2000 (n = 5,219) were interviewed biennially through 2010. Dementia probability, categorized in quartiles, was used to predict incident IADL limitations with Poisson regression. We estimated relative (risk ratio) and absolute (number of limitations) effects from models including dementia, individual-level modifiers (physical inactivity, smoking, no alcohol consumption, and depression) and interaction terms between dementia and individual-level modifiers.ResultsDementia probability quartile predicted incident IADL limitations (relative risk for highest versus lowest quartile = 0.44; 95% CI: 0.28-0.70). Most modifiers did not significantly increase risk of IADL limitations among the cognitively impaired. Physical inactivity (RR = 1.60; 95% CI: 1.16, 2.19) increased the risk of IADL limitations among the cognitively impaired. The interaction between physical inactivity and low dementia probability was statistically significant (p = 0.009) indicating that physical inactivity had significantly larger effects on incident IADLs among cognitively normal than among those with high dementia probability.ConclusionPhysical activity may protect against IADL limitations while not smoking, alcohol consumption, and not being depressed do not afford substantial protection among the cognitively impaired. RESULTS highlight the need for extra support for IADLs among individuals with cognitive losses

Do Physical Activity, Smoking, Drinking, or Depression Modify Transitions from Cognitive Impairment to Functional Disability?

Background: Individual-level modifiers can delay onset of limitations in basic activities of daily living (ADLs) among cognitively impaired individuals. We assessed whether these modifiers also delayed onset of limitations in instrumental ADLs (IADLs) among individuals at elevated dementia risk. Objectives: To determine whether modifiable individual-level factors delay incident IADL limitations among adults stratified by dementia risk. Methods: Health and Retirement Study participants aged 65+ without activity limitations in 1998 or 2000 (n = 5,219) were interviewed biennially through 2010. Dementia probability, categorized in quartiles, was used to predict incident IADL limitations with Poisson regression. We estimated relative (risk ratio) and absolute (number of limitations) effects from models including dementia, individual-level modifiers (physical inactivity, smoking, no alcohol consumption, and depression) and interaction terms between dementia and individual-level modifiers. Results: Dementia probability quartile predicted incident IADL limitations (relative risk for highest versus lowest quartile = 0.44; 95% CI: 0.28-0.70). Most modifiers did not significantly increase risk of IADL limitations among the cognitively impaired. Physical inactivity (RR = 1.60; 95% CI: 1.16, 2.19) increased the risk of IADL limitations among the cognitively impaired. The interaction between physical inactivity and low dementia probability was statistically significant (p = 0.009) indicating that physical inactivity had significantly larger effects on incident IADLs among cognitively normal than among those with high dementia probability. Conclusion: Physical activity may protect against IADL limitations while not smoking, alcohol consumption, and not being depressed do not afford substantial protection among the cognitively impaired. Results highlight the need for extra support for IADLs among individuals with cognitive losses.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000350001000012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701NeurosciencesSCI(E)[email protected]