The menopausal transition is an important life process, significantly impacting the cognitive and psychological health of women. Postmenopausal neuroimaging studies of hormone therapy indicate that estrogen levels have significant effects on brain neural circuitry. However, mechanistic studies of the neurobiology of the menopausal transition are lacking. This proposal combines the rich historical data from and access to a uniquely well-characterized population of women, transitioning the menopause, with neuropsychological testing and state-of-the-art neuroimaging techniques, to characterize the neurobiology of the menopausal transition. To test hypotheses concerning mechanisms of menopausal cognitive and affective changes, we will recruit from a well-characterized population of women at the mid-life who have been participants in a bone health and metabolism study involving extensive hormone and cycle monitoring since 1992. Recruits will be women aged 40-55 years, stratified into panels representing premenopause, early perimenopause, late perimenopause and natural postmenopause defined by follicle-stimulating hormone levels and menstrual bleeding patterns. This collaboration will involve extensive neuropsychological testing combined with a validated functional magnetic resonance (fMRI) imaging paradigm to determine brain activation patterns during cognitive and emotional tasks among women of each panel.
The Specific Aims i nclude: 1. Identify if specific stages or characteristics of the menopausal transition are associated with alterations in brain functioning as manifested either by fMRI-BOLD activation during cognitive and emotional tasks or by neuropsychological testing. 2. Delineate the relative contribution of ovarian aging vs. chronological aging in brain functioning as manifested either by fMRI-BOLD activation during cognitive and emotional tasks or by neuropsychological testing. 3. Demonstrate whether cognitive processing changes noted on fMRI-BOLD precede, occur concurrent, or follow observable changes in neuropsychological testing. These studies will determine the contributions of hormones and aging to changes in cognitive and emotional processing. A better understanding of the areas and sequence of brain processing changes will allow the health community to plan interventions which most effectively preserve cognitive and emotional health for women. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG027675-01
Application #
7067461
Study Section
Special Emphasis Panel (ZRG1-EMNR-J (50))
Program Officer
Wagster, Molly V
Project Start
2006-06-01
Project End
2010-03-31
Budget Start
2006-06-01
Budget End
2007-03-31
Support Year
1
Fiscal Year
2006
Total Cost
$312,113
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Berent-Spillson, Alison; Kelley, Angela S; Persad, Carol C et al. (2018) Postmenopausal hormone treatment alters neural pathways but does not improve verbal cognitive function. Menopause 25:1424-1431
Berent-Spillson, Alison; Marsh, Courtney; Persad, Carol et al. (2017) Metabolic and hormone influences on emotion processing during menopause. Psychoneuroendocrinology 76:218-225
Berent-Spillson, Alison; Persad, Carol C; Love, Tiffany et al. (2012) Hormonal environment affects cognition independent of age during the menopause transition. J Clin Endocrinol Metab 97:E1686-94
Shafir, Tal; Love, Tiffany; Berent-Spillson, Alison et al. (2012) Postmenopausal hormone use impact on emotion processing circuitry. Behav Brain Res 226:147-53
Smith, Yolanda R; Bowen, Luvina; Love, Tiffany M et al. (2011) Early initiation of hormone therapy in menopausal women is associated with increased hippocampal and posterior cingulate cholinergic activity. J Clin Endocrinol Metab 96:E1761-70
Berent-Spillson, Alison; Persad, Carol C; Love, Tiffany et al. (2010) Early menopausal hormone use influences brain regions used for visual working memory. Menopause 17:692-9