With the growing social and economic impact of dementia on the society, the emphasis is shifting from early diagnosis and treatment to the prevention of cognitive impairment and dementia. The social and economic implications of this epidemic will be greatest in women because of their longer life expectancy and elevated risk for dementia compared to men. Neuroprotective effects of estrogens offer the possibility of preventing or delaying mild cognitive impairment and dementia in postmenopausal women. However, oral conjugated equine estrogen treatment in older women who were more than a decade past their menopause did not prevent dementia, and there is controversy as to whether or not estrogen can preserve neurological function and decrease the risk of dementia when administered early in menopause defined as the ?critical window?. This project is proposed as a continuation to the Kronos Early Estrogen Prevention Study (KEEPS), a nationwide, multi-center, randomized blinded study of menopausal hormone therapy in newly postmenopausal women. Our objective is to assess the long-term risks and benefits of menopausal hormone therapy on Alzheimer's disease pathophysiology, cerebrovascular lesion load, cognitive and mood health in women who were treated with transdermal 17?-estradiol and oral conjugated equine estrogen compared to placebo within 36 months of their last menses; hypothesized as the ?critical window? for menopausal hormone therapy. Furthermore, we will investigate whether the Alzheimer's disease risk allele APOE ?4 and vascular risk factors influence the differences in A? deposition, brain structure, and cognition between each of the menopausal hormone therapy formulations and placebo, in order to provide insight into the mechanisms of cognitive and imaging biomarker changes associated with early menopausal hormone therapy. This project addresses an important and controversial problem regarding whether two commonly-used formulations of menopausal hormone therapy, administered during immediate postmenopausal years preserves cognition, neuronal integrity, and protects against cerebrovascular and Alzheimer's disease-related pathology. It is expected that the findings will hold the premise to significantly advance scientific knowledge and clinical practice by providing insight into the effects of early menopausal hormone therapy on long-term cognitive health.

Public Health Relevance

Prior studies have provided contradictory findings about the cognitive and mood effect of menopausal hormone therapies. The KEEPS Continuation Study will examine the long-term brain effects of menopausal hormone therapies in women approximately 8 years after they completed the clinical trial. The findings will provide critical safety and efficacy data on cognitive health, and inform millions of peri- and postmenopausal women as they consider whether to use hormone therapy to treat their menopausal symptoms.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Multi-Year Funded Research Project Grant (RF1)
Project #
1RF1AG057547-01
Application #
9422848
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Roberts, Luci
Project Start
2017-09-15
Project End
2022-06-30
Budget Start
2017-09-15
Budget End
2022-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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