Long-term amyloid PET and MRI outcomes in a menopausal hormone therapy trial

Authors

• Kejal Kantarci, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• Firat Kara, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• Nirubol Tosakulwong, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
• Angela J. Fought, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
• Christopher G. Schwarz, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• Matthew L. Senjem, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• June Kendall-Thomas, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• Paul Min, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• Val J. Lowe, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• Clifford R. Jack, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• Ekta Kapoor, Center for Women's Health, Mayo Clinic, Rochester, Minnesota, USA.
• Julie A. Fields, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
• Kent R. Bailey, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
• Taryn T. James, Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
• Laura Faubion, Department of Obstetrics and Gynecology, Marian Regional Medical Center, Santa Maria, California, USA.
• Rogerio A. Lobo, Department of Obstetrics and Gynecology, Columbia University, New York, New York, USA.
• JoAnn E. Manson, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Lubna Pal, Department of Obstetrics and Gynecology, Yale University, New Haven, Connecticut, USA.
• Dustin B. Hammers, Department of Neurology, Indiana University, Indianapolis, Indiana, USA.
• Eliot A. Brinton, Utah Lipid Center, Salt lake City, Utah, USA.
• Michael Malek-Ahmadi, Department of Neurology, Banner Alzheimer's Institute, Phoenix, Arizona, USA.
• Marcelle I. Cedars, Department of Obstetrics and Gynecology and Reproductive Sciences, University of California, San Francisco, California, USA.
• Frederick N. Naftolin, e-Bio Corp., New York, New York, USA.
• Nanette Santoro, Department of Obstetrics and Gynecology, University of Colorado, Aurora, Colorado, USA.
• Virginia M. Miller, Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
• Sherman M. Harman, Phoenix VA Health, University of Arizona College of Medicine, Phoenix, Arizona, USA.
• N Maritza Dowling, Department of Biostatistics, Department of Biostatistics & Bioinformatics, School of Nursing, Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia, USA.
• Carey E. Gleason, Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.

Document Type

Journal Article

Publication Date

2-1-2026

Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association

Volume

22

Issue

2

DOI

10.1002/alz.71067

Keywords

amyloid; estrogen; hormone therapy; magnetic resonance imaging; menopause; positron emission tomography

Abstract

INTRODUCTION: Associations of short-term use of menopausal hormone therapy (mHT) with Alzheimer's disease (AD) and structural magnetic resonance imaging (MRI) biomarkers were investigated 10 years after an mHT trial. METHODS: Recently menopausal women with good cardiovascular health were randomized to oral conjugated equine estrogens (oCEE) or transdermal 17β-estradiol (tE2) and micronized progesterone, or placebo for 4 years. Amyloid beta (Aβ) on positron emission tomography, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI were assessed 10 years after completion of the mHT trial (n = 266). RESULTS: Aβ and structural MRI biomarkers were not different in the oCEE and tE2 groups compared to placebo. Apolipoprotein E ε4 status did not modify the findings. DISCUSSION: There was no evidence of adverse effects or benefits associated with 4 years of use of oral or transdermal mHT on Aβ and structural MRI biomarkers in relatively healthy women, 10 years after mHT. Findings support the long-term safety of short-term use of mHT on brain health. CLINICAL TRIALS REGISTRATION: NCT00154180 Kronos Early Estrogen Prevention Study (KEEPS) HIGHLIGHTS: There were no menopausal hormone therapy-related adverse effects or benefits on amyloid beta and magnetic resonance imaging biomarkers in the long term. Apolipoprotein E ε4 carrier status did not modify these findings. Findings align with neutral cognitive and cerebrovascular outcomes in this cohort.

APA Citation

Kantarci, Kejal; Kara, Firat; Tosakulwong, Nirubol; Fought, Angela J.; Schwarz, Christopher G.; Senjem, Matthew L.; Kendall-Thomas, June; Min, Paul; Lowe, Val J.; Jack, Clifford R.; Kapoor, Ekta; Fields, Julie A.; Bailey, Kent R.; James, Taryn T.; Faubion, Laura; Lobo, Rogerio A.; Manson, JoAnn E.; Pal, Lubna; Hammers, Dustin B.; Brinton, Eliot A.; Malek-Ahmadi, Michael; Cedars, Marcelle I.; Naftolin, Frederick N.; Santoro, Nanette; Miller, Virginia M.; Harman, Sherman M.; Dowling, N Maritza; and Gleason, Carey E., "Long-term amyloid PET and MRI outcomes in a menopausal hormone therapy trial" (2026). GW Authored Works. Paper 8776.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8776

Department

Nursing Faculty Publications