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Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women
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OBJECTIVE: To determine the association between age at surgical menopause and both cognitive decline and Alzheimer disease (AD) pathology in 2 longitudinal cohorts. METHODS: Female subjects from 2 longitudinal studies of cognitive decline (Religious Orders Study and Rush Memory and Aging Project) were included (total n = 1,884). The primary analysis examined the association between age at surgical menopause and decline in a global cognition score. Secondary analyses examined additional outcomes: 1) decline in 5 cognitive subdomains and 2) a global measure of the burden of AD pathology. In exploratory analyses, we examined the effect of hormone replacement therapy (HRT). We adjusted all models for age, education, smoking, and cohort and stratified by surgical vs natural menopause. RESULTS: For the 32% of subjects with surgical menopause, earlier age at menopause was associated with faster decline in global cognition (p = 0.0007), specifically episodic memory (p = 0.0003) and semantic memory (p = 0.002). Earlier age at menopause was also associated with increased AD neuropathology (p = 0.038), in particular neuritic plaques (p = 0.013). HRT use for at least 10 years, when administered within a 5-year perimenopausal window, was associated with decreased decline in global cognition. No associations were seen in women who had natural menopause. CONCLUSIONS: Early age at surgical menopause was associated with cognitive decline and AD neuropathology. Ongoing studies should clarify the potential effect of HRT on this relationship.
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“In prior work, we found that women, a subset of those in the current study, who had surgical menopause at an early age had a faster decline in cognitive function and more AD pathology at autopsy, and neuritic plaques in particular, compared to women with surgical menopause at older ages [14].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [14]
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“Yet, clinical longitudinal studies have shown susceptibility of women with surgical menopause at young ages to cognitive decline [14] and dementia [52].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [14]
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“In our previous study, we found that younger age at onset of menopause among women with surgical, not natural, menopause was associated with more AD pathologies [14].”
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“Some evidence suggests that early menopause induced by oophorectomy are AD risk factors specific to women [513].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [513]
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Metadata
- Authors
- Bove, R., Secor, E., Chibnik, L. B., Barnes, L. L., Schneider, J. A., Bennett, D. A., & De Jager, P. L.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Program in Translational NeuroPsychiatric Genomics (R.B., E.S., L.B.C., P.L.D.), Institute for the Neurosciences, Department of Neurology, Brigham and Women’s Hospital; Harvard Medical School (R.B., L.B.C., P.L.D.), Boston, MA; and the Departments of Neurological Sciences (L.L.B.) and Neuropathology (J.A.S., D.A.B.), Rush University Medical Center, Chicago, IL.
- Venue
- Neurology
- Published
- 2014-01-21
- Volume
- 82
- Issue
- 3
- Pages
- 222-229
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3902759
- OpenAlex
- W2027439763
- Cited by
- 437
- References
- 43
- Citations by year
- 2026: 30 · 2025: 53 · 2024: 50 · 2023: 64 · 2022: 29 · 2021: 41 · 2020: 34 · 2019: 41 · 2018: 28 · 2017: 15 · 2016: 24 · 2015: 13 · 2014: 14
- FWCI
- 13.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Biogen
- Teva Pharmaceutical Industries
- Danone
- Avid Radiopharmaceuticals
- National Institute on Aging (R01AG017917, K25AG041906, R01AG030146, K08AG034290, R01AG015819, P30AG010161, R01AG022018)
- National Institute of Allergy and Infectious Diseases (T32AI074549)
- National Institute of Neurological Disorders and Stroke (R01NS059873)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- surgical menopause, age at menopause, cognitive decline, Alzheimer disease pathology, hormone replacement therapy, episodic memory, semantic memory, neuritic plaques, older women, natural menopause, perimenopause
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Cognition Disorders, Female, Health Surveys, Humans, Longitudinal Studies, Memory Disorders, Menopause, Middle Aged, Single-Blind Method, Treatment Outcome, Hormone Replacement Therapy, Plaque, Amyloid, Memory, Episodic
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