Our goals are: 1. To describe the course of differential brain aging with a focus on the best-case-scenario naturalistic study of successful aging. The proposed 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 uncontrolled human population. 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 basal metabolism in the gray matter. We plan to examine whether regional brain shrinkage is associated with reduced integrity of the underlymg white matter and reduced local vascular activity. We wil assess white matter integrity by measuring the extent of leukoaraiosis and by gauging intactness of the myelinated fibers through diffusion tensor (DTI) and magnetization transfer (MT) imaging. Local vascular changes will be assessed by measuring local T2* relaxation constants that are related to the degree of blood oxygenation. We will introduce new imaging method - multi-echo Susceptibility Weighted Imaging (SWI) that allow measurement of T2* and local field variations with better precision and resolution that by conventional gradient-recall methods. 3 To evaluate the links between age-related regional brain changes (volume, diffusion and magnetization properties, and basal metabolism) and performance in three cognitive domains with known vulnerability to aging: episodic memory, executive functions, and speed of processing. 4. To examine the effect of modifiers of brain and cognitive aging - the vascular risk and genetic factors on differential brain and cognitive aging. By examining the possibility of dose-response effect of vascular risk factors on adult brain and cognition we hope to provide the data against which pathology will be understood. Because some of the women who participate in the study will be on hormone replacement therapy (HRT), we will assess the potential benefits of HRT on brain aging. The modifying role of ApoE genotype in shaping the trafectories of brain and cognitive againg will be also assessed. 5. Finally, common to all listed aims is a longitudinal approach to study of biological and cognitive change. To attain that overriding goal, we plan to apply longitudinal latent-variable growth modeling techniques to the analysis of our data. The innovative aspect of that approach is that those techniques are the staple of demographic, social, and cognitive aging studies. We expect these modeling techniques will allow testing hypotheses about relations between regional brain changes and specific cognitive skills in healthy aging adults. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37AG011230-11A1
Application #
6927406
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Wagster, Molly V
Project Start
1993-09-30
Project End
2010-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
11
Fiscal Year
2005
Total Cost
$603,471
Indirect Cost
Name
Wayne State University
Department
Type
Organized Research Units
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Raz, Naftali; Daugherty, Ana M (2018) Pathways to Brain Aging and Their Modifiers: Free-Radical-Induced Energetic and Neural Decline in Senescence (FRIENDS) Model - A Mini-Review. Gerontology 64:49-57
Yuan, Peng; Voelkle, Manuel C; Raz, Naftali (2018) Fluid intelligence and gross structural properties of the cerebral cortex in middle-aged and older adults: A multi-occasion longitudinal study. Neuroimage 172:21-30
Hect, Jasmine L; Daugherty, Ana M; Hermez, Klodia M et al. (2018) Developmental variation in regional brain iron and its relation to cognitive functions in childhood. Dev Cogn Neurosci 34:18-26
Daugherty, Ana M; Raz, Naftali (2017) A virtual water maze revisited: Two-year changes in navigation performance and their neural correlates in healthy adults. Neuroimage 146:492-506
Bender, Andrew R; Naveh-Benjamin, Moshe; Amann, Katheryn et al. (2017) The role of stimulus complexity and salience in memory for face-name associations in healthy adults: Friend or foe? Psychol Aging 32:489-505
Trifan, Gabriela; Gattu, Ramtilak; Haacke, Ewart Mark et al. (2017) MR imaging findings in mild traumatic brain injury with persistent neurological impairment. Magn Reson Imaging 37:243-251
Wisse, Laura E M; Daugherty, Ana M; Olsen, Rosanna K et al. (2017) A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals? Hippocampus 27:3-11
Viviano, Raymond P; Raz, Naftali; Yuan, Peng et al. (2017) Associations between dynamic functional connectivity and age, metabolic risk, and cognitive performance. Neurobiol Aging 59:135-143
Daugherty, Ana M; Raz, Naftali (2017) Incident risk and progression of cerebral microbleeds in healthy adults: a multi-occasion longitudinal study. Neurobiol Aging 59:22-29
Arshad, Muzamil; Stanley, Jeffrey A; Raz, Naftali (2017) Test-retest reliability and concurrent validity of in vivo myelin content indices: Myelin water fraction and calibrated T1 w/T2 w image ratio. Hum Brain Mapp 38:1780-1790

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