Dataset Information

Association of Aortic Stiffness With Cognition and Brain Aging in Young and Middle-Aged Adults: The Framingham Third Generation Cohort Study.

ABSTRACT: Aortic stiffness is associated with cognitive decline and cerebrovascular disease late in life, although these associations have not been examined in young adults. Understanding the effects of aortic stiffness on the brain at a young age is important both from a pathophysiological and public health perspective. The aim of this study was to examine the cross-sectional associations of aortic stiffness with cognitive function and brain aging in the Framingham Heart Study Third Generation cohort (47% men; mean age, 46 years). Participants completed the assessment of aortic stiffness (carotid-femoral pulse wave velocity), a neuropsychological test battery assessing multiple domains of cognitive performance and magnetic resonance imaging to examine subclinical markers of brain injury. In adjusted regression models, higher aortic stiffness was associated with poorer processing speed and executive function (Trail Making B-A; ?±SE, -0.08±0.03; P<0.01), larger lateral ventricular volumes (?±SE, 0.09±0.03; P<0.01) and a greater burden of white-matter hyperintensities (?±SE, 0.09±0.03; P<0.001). When stratifying by age, aortic stiffness was associated with lateral ventricular volume in young adults (30-45 years), whereas aortic stiffness was associated with white-matter injury and cognition in midlife (45-65 years). In conclusion, aortic stiffness was associated with cognitive function and markers of subclinical brain injury in young to middle-aged adults. Prospective studies are needed to examine whether aortic stiffening in young adulthood is associated with vascular cognitive impairment later in life.

SUBMITTER: Pase MP

PROVIDER: S-EPMC4752398 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Association of Aortic Stiffness With Cognition and Brain Aging in Young and Middle-Aged Adults: The Framingham Third Generation Cohort Study.

Pase Matthew P MP Himali Jayandra J JJ Mitchell Gary F GF Beiser Alexa A Maillard Pauline P Tsao Connie C Larson Martin G MG DeCarli Charles C Vasan Ramachandran S RS Seshadri Sudha S

Hypertension (Dallas, Tex. : 1979) 20160111 3

Aortic stiffness is associated with cognitive decline and cerebrovascular disease late in life, although these associations have not been examined in young adults. Understanding the effects of aortic stiffness on the brain at a young age is important both from a pathophysiological and public health perspective. The aim of this study was to examine the cross-sectional associations of aortic stiffness with cognitive function and brain aging in the Framingham Heart Study Third Generation cohort (47 ...[more]

PMID: 26754644

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Project description:Background Chronological aging-associated changes in the human DNA methylome are studied by multiple epigenome-wide association studies (EWAS); however, the aging-associated DNAmet changes identified among different age groups and tissues vary and especially the rates of aging-associated alterations in the epigenome during adulthood remain unclear. Here, we further explore and characterize CpG-sites where DNA methylation levels alter at a constant rate during adulthood and are also independent of blood cell type heterogeneity. Results In the study, we observed 1,202 aging-associated CpG-sites (a-CpGs), of which 48% were hypermethylated with advancing age in whole blood with an especially narrow age range (40 - 49 years). Repeatedly reported a-CpGs in ELOVL2, FHL2, PENK and KLF14 were also identified. Regions with aging-associated hypermethylation were enriched to several gene ontology terms (especially on the cluster of developmental processes), while hypomethylated sites showed no enrichment. The genes with a higher number of a-CpG hits were more often hypermethylated. Of the 1,202 aging-associated CpG-sites in the present study, 987 were identified in previous study (Vitality 90+) as differentially methylated also between nonagenarians and young adults in a previous study, and importantly, the directions of changes were identical in the previous and in the present study. Conclusions The set of 987 replicated a-CpGs presented here are altered in strong association with chronological aging in the whole range of adulthood. Consequently, future studies should note the variability of the types of a-CpGs, and the a-CpGs presented here should be dissociated from the environmental-sensitive CpG-sites or from regions that are associated with aging in a non-linear manner due to the accumulation of senescence-related features. This report offers detailed and verified pool of a-CpGs in which DNAmet levels associate linearly with chronological age and of which are different from the non-linearly changing ones.

Project description:Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging associated frailty may preclude physical activity. AMP-activated protein kinase (AMPK) is a transcriptional regulator important for muscle physiology. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (2-month-old), aged (23-month-old) C57Bl/6 mice, and transgenic mice with muscle-specific mutated AMPK alpha-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3 to 14 days and tested in the Morris water maze, rotarod and open field. Improved water maze performance and motor function was observed, albeit at longer duration of administration, in aged (14 days AICAR) than young (3 days AICAR) mice. In the AMPKDN mice, the compound did not enhance behavior, providing support for a muscle mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus genes relevant to neuronal development and plasticity were enriched. Altogether, endurance related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions. Key words: Skeletal Muscle, Brain, Exercise, AMPK, Learning and Memory, Morris water maze 23-month old female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME) were housed under standard conditions, 3 mice per cage, with food and water ad libitum. Mice were injected intraperitoneally with 5-Aminoimidazole-4-carboxamide-1-a-D-ribofuranoside (AICAR, Toronto Research Chemicals Inc., Canada) dissolved in saline, 500 mg/kg/day for 3 (ACR3), 7 (ACR7) or 14 (ACR14) days or saline vehicle, for 3 (CTR) days. Thirty-three days after the final injection animals were deeply anesthetized with isofluorane and perfused transcardially with 0.9% NaCl solution. The gastrocnemius muscle and Hippocampus were quickly removed, frozen on dry ice and stored at M-bM-^HM-^R80 M-BM-0C for RNA isolation and microarray analysis.

Dataset Information

Association of Aortic Stiffness With Cognition and Brain Aging in Young and Middle-Aged Adults: The Framingham Third Generation Cohort Study.

Publications

Association of Aortic Stiffness With Cognition and Brain Aging in Young and Middle-Aged Adults: The Framingham Third Generation Cohort Study.

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