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Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging
Open accessAbstract
Objective: This observational multimodality brain imaging study investigates emergence of endophenotypes of late-onset Alzheimer disease (AD) risk during endocrine transition states in a cohort of clinically and cognitively normal women and age-matched men. Methods: Forty-two 40- to 60-year-old cognitively normal women (15 asymptomatic perimenopausal by age [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age- and education-matched men were examined. All patients had volumetric MRI, 18F-fluoro-2-deoxyglucose (FDG)–PET (glucose metabolism), and Pittsburgh compound B–PET scans (β-amyloid [Aβ] deposition, a hallmark of AD pathology). Results: As expected, the MENO group was older than the PERI and CNT groups. Otherwise, groups were comparable on clinical and neuropsychological measures and APOE4 distribution. Compared to CNT women and to men, and controlling for age, PERI and MENO groups exhibited increased indicators of AD endophenotype, including hypometabolism, increased Aβ deposition, and reduced gray and white matter volumes in AD-vulnerable regions (p < 0.001). AD biomarker abnormalities were greatest in MENO, intermediate in PERI, and lowest in CNT women (p < 0.001). Aβ deposition was exacerbated in APOE4-positive MENO women relative to the other groups (p < 0.001). Conclusions: Multimodality brain imaging indicates sex differences in development of the AD endophenotype, suggesting that the preclinical AD phase is early in the female aging process and coincides with the endocrine transition of perimenopause. These data indicate that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process.
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“although mounting evidence suggests that women are at heightened risk for exhibiting AD pathophysiology.5–8”
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“Minimal,6 if any,11,12,36 sex differences have been found cross sectionally in levels of global Aβ burden in clinically normal older adults”
From Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults (2019) · cites this paper as [6]
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References 43 · Cited by 319
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Metadata
- Authors
- Mosconi, L., Berti, V., Quinn, C., McHugh, P., Petrongolo, G., Varsavsky, I., Osorio, R. S., Pupi, A., Vallabhajosula, S., Isaacson, R. S., de Leon, M. J., & Brinton, R. D.
- Affiliations
- University of Southern California (US)
- From the Departments of Neurology (L.M., R.S.I.) and Radiology (S.V.), Weill Cornell Medical College; Department of Psychiatry (L.M., C.Q., P.M., G.P., I.V., R.S.O., M.J.d.L.), New York University School of Medicine, New York; Department of Biomedical, Experimental and Clinical Sciences “Mario Serio” (V.B., A.P.), Nuclear Medicine Unit, University of Florence, Italy; Departments of Pharmacology and Neurology (R.D.B.), College of Medicine, University of Arizona, Tucson; and Departments of...
- ORCID
- Venue
- Neurology
- Published
- 2017-09-26
- Volume
- 89
- Issue
- 13
- Pages
- 1382-1390
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC5652968
- OpenAlex
- W2751377372
- Cited by
- 319
- References
- 43
- Citations by year
- 2026: 45 · 2025: 59 · 2024: 45 · 2023: 38 · 2022: 28 · 2021: 36 · 2020: 27 · 2019: 20 · 2018: 21
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- National Institute on Aging (R01AG022374, P30AG008051, R01AG013616, P01AG026572, R01AG035137)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- Alzheimer's disease, sex differences, perimenopause, menopause, endophenotypes, preclinical Alzheimer's disease, amyloid-beta deposition, hypometabolism, gray and white matter volume, APOE ε4, brain aging
- MeSH terms
- Adult, Aging, Alzheimer Disease, Apolipoproteins E, Brain, Endocrine System, Female, Glucose, Humans, Magnetic Resonance Imaging, Male, Menopause, Middle Aged, Organ Size, Risk, Sex Characteristics, Biomarkers, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography, Endophenotypes, Multimodal Imaging
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