The goals of this continuing project are 1.
Aim 1. To describe the course of differential brain aging vyith a focus on the best-case-scenario naturalistic study of successful aging. With that focus, the study will complement existing large-scale longitudinal investigations of typical geriatric samples. Our objective is to examine the closest approximation to successful physiological aging to be found in an unselected human population. 2.
Aim 2, To gain insights into mechanisms of age-related differential brain shrinkage by examining changes in microstructure of the white matter and indirect indices of regional brain iron content. 3.
Aim 3. To evaluate the links between age-related regional brain changes (volume, diffusion and magnetization properties, and iron content) and performance in three cognitive domains with known vulnerability to aging: episodic memory, executive functions, and speed of processing. 4.
Aim 4. To examine the effect of vascular risk factors (physiological and genetic) as modifiers of brain and cognitive aging. We will continue our investigation into the effects of sub-clinical levels of vascular risk conveyed by elevated blood pressure, circulating cardiac risk factors (homocysteine, C-reactive protein), elevated insulin, and genetic variants associated with vascular and metabolic risk (MTHFR C677T, IL1-p C511T, BDNF Val66Met, ACE l/D, ApoEpound4, diabetes risk genes, and polymorphisms related to specific neurotransmitters - acetylcholine, serotonin, dopamine).
Aim 5. Common to all listed aims is a longitudinal approach to study of biological and cognitive change with Latent Growth Curves models that allow estimation of the shape of the trajectories of aging.
Aim 6. Methodological contributions. During the proposed extension award period, we plan to initiate several methodological investigations, in which we will compared manual volumetry and ROI-based evaluation of white matter integrity with various semi-automated methods, with a hope to improve those methods to the level comparable with the "golden standard."

Public Health Relevance

The proposed project is directly related to the mission of the NIA which to improve the health and well-being of older Americans through research. More specifically, the results of this project will highlight the contrast between healthy aging and age-related diseases such as Alzheimer's and vascular dementia and will contribute to understanding individual variability of aging in the context of genetics and neurobiology

National Institute of Health (NIH)
National Institute on Aging (NIA)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Wagster, Molly V
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Wayne State University
Schools of Arts and Sciences
United States
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Raz, Naftali; Daugherty, Ana M; Bender, Andrew R et al. (2015) Volume of the hippocampal subfields in healthy adults: differential associations with age and a pro-inflammatory genetic variant. Brain Struct Funct 220:2663-74
Sethi, Sean K; Utriainen, David T; Daugherty, Ana M et al. (2015) Jugular Venous Flow Abnormalities in Multiple Sclerosis Patients Compared to Normal Controls. J Neuroimaging 25:600-7
Yuan, Peng; Daugherty, Ana M; Raz, Naftali (2014) Turning bias in virtual spatial navigation: age-related differences and neuroanatomical correlates. Biol Psychol 96:8-19
Yuan, Peng; Raz, Naftali (2014) Prefrontal cortex and executive functions in healthy adults: a meta-analysis of structural neuroimaging studies. Neurosci Biobehav Rev 42:180-92
Raz, Naftali; Lustig, Cindy (2014) Genetic variants and cognitive aging: destiny or a nudge? Psychol Aging 29:359-62
Alosco, Michael L; Spitznagel, Mary Beth; Raz, Naftali et al. (2014) Executive dysfunction is independently associated with reduced functional independence in heart failure. J Clin Nurs 23:829-36
Alosco, Michael L; Spitznagel, Mary Beth; Cohen, Ronald et al. (2014) Decreased physical activity predicts cognitive dysfunction and reduced cerebral blood flow in heart failure. J Neurol Sci 339:169-75
Alosco, Michael L; Garcia, Sarah; Spitznagel, Mary Beth et al. (2014) Cognitive performance in older adults with stable heart failure: longitudinal evidence for stability and improvement. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 21:239-56
Persson, N; Ghisletta, P; Dahle, C L et al. (2014) Regional brain shrinkage over two years: individual differences and effects of pro-inflammatory genetic polymorphisms. Neuroimage 103:334-48
Bender, Andrew R; Daugherty, Ana M; Raz, Naftali (2013) Vascular risk moderates associations between hippocampal subfield volumes and memory. J Cogn Neurosci 25:1851-62

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