Dataset Information

Neighborhood Predictors of Cognitive Training Outcomes and Trajectories in ACTIVE.

ABSTRACT: We examined the influence of neighborhood socioeconomic position (SEP), racial/ethnic composition, and living in a major city on cognitive trajectories and intervention outcomes. Data came from the Advanced Cognitive Training for Independent and Vital Elderly study ( N = 2,438). Mixed effects analyses examined the associations between neighborhood variables and memory, reasoning, speed of processing, and everyday cognition, estimating differences in initial gains (potentially related to practice) and long-term rate of change over 10 years. The effect of reasoning training on initial gain was weaker for individuals in a major city. For everyday cognition, there was a stronger initial gain for memory-trained and control participants in areas with more racial/ethnic minorities and for speed-trained and control individuals in higher SEP areas. The racial/ethnic minority effect was no longer significant after adjustment for multiple comparisons. Neighborhood factors may be more important in practice-related improvement than in long-term change.

SUBMITTER: Meyer OL

PROVIDER: S-EPMC4905811 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Neighborhood Predictors of Cognitive Training Outcomes and Trajectories in ACTIVE.

Meyer Oanh L OL Sisco Shannon M SM Harvey Danielle D Zahodne Laura B LB Glymour M Maria MM Manly Jennifer J JJ Marsiske Michael M

Research on aging 20160803 3

We examined the influence of neighborhood socioeconomic position (SEP), racial/ethnic composition, and living in a major city on cognitive trajectories and intervention outcomes. Data came from the Advanced Cognitive Training for Independent and Vital Elderly study ( N = 2,438). Mixed effects analyses examined the associations between neighborhood variables and memory, reasoning, speed of processing, and everyday cognition, estimating differences in initial gains (potentially related to practice ...[more]

PMID: 26667987

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Project description:Background: Numerous studies have focused on the PI3K/AKT/mTOR pathway in estrogen receptor positive (ER) breast cancer (BC), as a linear signal transduction pathway and reported its association with worse clinical outcomes. To gain better insight into the relative contribution of each of the signalling pathways which lie downstream to PI3K (namely AKT and mTOR) to BC outcomes, we have developed a novel in silico approach which assessed the activation of each of these signalling pathways separately. Methods: By analysing gene expression and matched proteomic data in ER-positive patients from the TCGA repository, we developed gene signatures that reflect the level of expression of phosphorylated-Serine473-AKT (pAKT) and phosphorylated-Serine2448-mTOR (p-mTOR) separately, capturing their corresponding level of pathway activation. Using pooled analysis of gene-expression data from over 7,000 patients with ER-positive early BC, we then investigated the association between pathway activation and outcomes. Results: Our analysis revealed that the pAKT pathway activation (as measured by the developed signature) was associated with luminal A BC while the p-mTOR pathway activation was more associated with luminal B BC (Kruskal-Wallis test p<10-10). pAKT pathway activation was significantly associated with better outcomes (multivariable HR, 0.79; 95% CI, 0.74 to 0.85; p=2.5x10-10) whereas p-mTOR pathway activation showed worse outcomes (multivariable HR, 1.1; 95% CI, 1.1 to 1.2; p=9.9x10-4). Similar associations between activation and outcomes were obtained when the analysis was performed in patients who were treated with hormonal therapy. Additionally, pAKT pathway activation predicted better outcomes irrespective of the BC molecular subtypes (luminal A multivariable HR, 0.85; 95% CI, 0.75 to 0.96; p=0.01; luminal B HR, 0.91; 95% CI, 0.83 to 0.99; p=0.033). pAKT pathway activation was associated with PIK3CA mutations (p=0.0001) while p-mTOR pathway activation was associated with p53 mutations (p=0.04). Finally, we show that pAKT pathway activation was associated with less response to Everolimus. Conclusions: Our data show that pAKT and p-mTOR pathway activation have differing impact on prognosis and suggest that they are not linearly connected in luminal breast cancers. These findings add to our understanding of signalling through the PI3K pathway and could have important implications for the treatment of luminal BC.

Dataset Information

Neighborhood Predictors of Cognitive Training Outcomes and Trajectories in ACTIVE.

Publications

Neighborhood Predictors of Cognitive Training Outcomes and Trajectories in ACTIVE.

Similar Datasets

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