IC-P-108: WHITE MATTER HYPERINTENSITIES IN RELATION TO PATTERNS OF ACCELERATED BRAIN AGING, AD-LIKE ATROPHY AND AMYLOID BURDEN: RESULTS FROM THE ISTAGING CONSORTIUM ON MACHINE LEARNING AND LARGE-SCALE IMAGING ANALYTICS

Objective:To test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI.Methods:We studied 492 participants (58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE4 carrier status, stroke risk factors, sleeping pill use, body mass index and depression.Results:Less slow-wave sleep was associated with lower cortical brain volume (absolute duration, β[standard error]: 0.20[0.08], p=0.015; percentage, 0.16[0.08], p=0.044), lower subcortical brain volume (percentage, 0.03[0.02], p=0.034), and higher white matter hyperintensities volume (absolute duration, -0.12[0.05], p=0.010; percentage -0.10[0.04], p=0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts.Conclusion:Loss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.

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Abstract MP46: Growth Factors Are Associated With Imaging Markers of Brain Aging in Young Adults

Circulation ◽

10.1161/circ.131.suppl_1.mp46 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Claudia L Satizabal ◽

Alexa Beiser ◽

Jayandra J Himali ◽

Rhoda Au ◽

Philip A Wolf ◽

...

Keyword(s):

Young Adults ◽

Growth Factors ◽

White Matter ◽

Growth Factor ◽

White Matter Hyperintensities ◽

Brain Aging ◽

Brain Mri ◽

Blood Draw ◽

Brain Volumes ◽

Angiopoietin 2

Metabolic and vascular dysregulation are related to stroke, cognitive decline and dementia. Growth factor biomarkers of these processes, such as Insulin-like Growth Factor 1 (IGF1) and Vascular Endothelial Growth Factor (VEGF) have been associated with risk of neurodegeneration and stroke in middle-aged and older Framingham participants. Additionally, hepatocyte growth factor (HGF) and angiopoietin 2 are novel biomarkers of interest as they have been related to cardiovascular events. As abnormal brain changes probably start years before clinical symptoms, we hypothesize that circulating growth factors are related to MRI endophenotypes of brain aging. We included 1,877 individuals aged 46±8 years from the Framingham Study. Blood samples were collected during 2008-2011, and used to measure IGF1, VEGF, HGF, angiopoietin 2 and its receptor tyrosine kinase (TIE2). Participants underwent brain MRI examination (2009-2013) from which brain volumes and white matter hyperintensities were estimated. We related growth factor levels to brain MRI markers adjusting for age, sex, time between blood draw and MRI, and cardiovascular risk factors. Lower IGF1, as well as higher HGF and angiopoietin 2 levels were associated with higher ventricular volumes indicative of brain shrinkage. Higher TIE2 levels were associated with lower total brain and gray matter volumes, while higher angiopoietin 2 levels were associated with lower white matter volumes. Lower IGF1 levels were also associated with reduced hippocampal volumes. Finally, higher TIE2 levels were associated with larger white matter hyperintensities. Our results suggest that growth factors are associated with neurodegenerative and cerebrovascular markers of brain aging in healthy young adults. Whereas IGF1 seems protective, higher levels of HGF, angiopoietin 2 and TIE2 were associated with greater subclinical brain injury. These associations expand our understanding of the earliest stages of brain aging. We will extend our findings by analyzing cognitive outcomes.

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