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- W2895835858 abstract "Aging is the primary risk factor for both Alzheimer's disease and cardiovascular disease (CVD). Previously, we identified two age-related transcriptional networks related to autophagic flux and mitochondrial bioenergetics, two fundamental aging mechanisms. Our objective is to identify age-related transcriptional networks that are associated with both pulse pressure and cognitive function. We examined the cross-sectional relationships of the autophagic flux (3 transcripts) mitochondrial bioenergetics transcriptional network (205 transcripts) with pulse pressure and cognitive function at the 2010-2012 Multi-Ethnic Study of Atherosclerosis (MESA) examination in 1,264 community-based adults, 47% Caucasian, 32% Hispanic, 21% African American, 51% female, aged 55–94 years. Transcriptional profiles in monocytes, isolated with anti-CD14 monoclonal antibody coated magnetic beads, were quantified by the Illumina HumanHT-12 v4 Expression BeadChip. A global cognitive composite score was constructed by averaging each participant's standardized z-scores from three cognitive tests: Cognitive Abilities Screening Instrument, Digit Symbol Coding and Digit Span tests. The eigengene score was defined as the first principal component of a transcriptional network. Multivariable linear regression model was used with pulse pressure and cognitive function as outcomes. Older adults, persons with less education, CVD, hypertension, and type 2 diabetes had lower cognitive composite scores. The eigengene score of the autophagic network was positively associated with pulse pressure and inversely associated with cognitive function, after adjusting for age, gender, ethnicity, and study site (Table). After additional adjustment for education, physical activity, smoking, alcohol use, body mass index, type-2 diabetes, hypertension, and cardiovascular disease, the associations were attenuated but remained statistically significant. These associations were qualitatively consistent across gender and ethnicity subgroups (p for interactions>0.05). Two autophagic genes, MCL1 and TSC22D3, but not CEBPD, were associated with both pulse pressure (beta=5.77, p=0.0002 for MCL1; beta=2.97, p=0.006) and cognitive function (beta=-1.82, p=0.004; beta=-1.36, p=0.002), in fully adjusted models. The mitochondrial network was positively associated with cognitive function, but not pulse pressure. The relationships of the autophagic flux gene network to both pulse pressure and cognitive function support the notion that common mechanisms of the biological aging underlie both age-related vascular and cognitive dysfunction." @default.
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- W2895835858 date "2018-07-01" @default.
- W2895835858 modified "2023-10-16" @default.
- W2895835858 title "P3‐115: THE ASSOCIATIONS OF AGE‐RELATED TRANSCRIPTIONAL NETWORKS WITH VASCULAR AND COGNITIVE FUNCTION: THE MULTI‐ETHNIC STUDY OF ATHEROSCLEROSIS" @default.
- W2895835858 doi "https://doi.org/10.1016/j.jalz.2018.06.1472" @default.
- W2895835858 hasPublicationYear "2018" @default.
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