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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Bender, Andrew R; Völkle, Manuel C; Raz, Naftali (2016) Differential aging of cerebral white matter in middle-aged and older adults: A seven-year follow-up. Neuroimage 125:74-83
Arshad, Muzamil; Stanley, Jeffrey A; Raz, Naftali (2016) Adult age differences in subcortical myelin content are consistent with protracted myelination and unrelated to diffusion tensor imaging indices. Neuroimage 143:26-39
Damoiseaux, Jessica S; Viviano, Raymond P; Yuan, Peng et al. (2016) Differential effect of age on posterior and anterior hippocampal functional connectivity. Neuroimage 133:468-76
Daugherty, Ana M; Bender, Andrew R; Raz, Naftali et al. (2016) Age differences in hippocampal subfield volumes from childhood to late adulthood. Hippocampus 26:220-8
Daugherty, Ana M; Raz, Naftali (2016) A virtual water maze revisited: Two-year changes in navigation performance and their neural correlates in healthy adults. Neuroimage :
Daugherty, Ana M; Raz, Naftali (2016) Accumulation of iron in the putamen predicts its shrinkage in healthy older adults: A multi-occasion longitudinal study. Neuroimage 128:11-20
Persson, Ninni; Ghisletta, Paolo; Dahle, Cheryl L et al. (2016) Regional brain shrinkage and change in cognitive performance over two years: The bidirectional influences of the brain and cognitive reserve factors. Neuroimage 126:15-26
Bender, Andrew R; Prindle, John J; Brandmaier, Andreas M et al. (2016) White matter and memory in healthy adults: Coupled changes over two years. Neuroimage 131:193-204
Daugherty, Ana M; Raz, Naftali (2015) Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods. Neuropsychol Rev 25:272-87
Yang, Yiqin; Bender, Andrew R; Raz, Naftali (2015) Age related differences in reaction time components and diffusion properties of normal-appearing white matter in healthy adults. Neuropsychologia 66:246-58

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