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Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging.

TitleSex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging.
Publication TypeJournal Article
Year of Publication2017
AuthorsMosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Varsavsky I, Osorio RS, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Brinton RDiaz
JournalNeurology
Volume89
Issue13
Pagination1382-1390
Date Published2017 Sep 26
ISSN1526-632X
KeywordsAdult, Aging, Alzheimer Disease, Apolipoproteins E, Biomarkers, Brain, Endocrine System, Endophenotypes, Female, Fluorodeoxyglucose F18, Glucose, Humans, Magnetic Resonance Imaging, Male, Menopause, Middle Aged, Multimodal Imaging, Organ Size, Positron-Emission Tomography, Radiopharmaceuticals, Risk, Sex Characteristics
Abstract

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, F-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 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 ( < 0.001). AD biomarker abnormalities were greatest in MENO, intermediate in PERI, and lowest in CNT women ( < 0.001). Aβ deposition was exacerbated in -positive MENO women relative to the other groups ( < 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.

DOI10.1212/WNL.0000000000004425
Alternate JournalNeurology
PubMed ID28855400
PubMed Central IDPMC5652968
Grant ListP01 AG026572 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
R01 AG022374 / AG / NIA NIH HHS / United States

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