Sex differences in Alzheimer risk
| Autor: | Ricardo S. Osorio, Roberta Diaz Brinton, Lisa Mosconi, Richard S. Isaacson, Shankar Vallabhajosula, Mony J. de Leon, Crystal Quinn, Isabella Varsavsky, Pauline McHugh, Alberto Pupi, Valentina Berti, Gabriella Petrongolo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Risk 0301 basic medicine Oncology Gerontology Aging medicine.medical_specialty Endophenotypes Peri Endocrine System Multimodal Imaging Asymptomatic Article White matter 03 medical and health sciences Apolipoproteins E 0302 clinical medicine Alzheimer Disease Fluorodeoxyglucose F18 Internal medicine medicine Humans Endocrine system Sex Characteristics business.industry Brain Organ Size Middle Aged medicine.disease Magnetic Resonance Imaging Glucose 030104 developmental biology medicine.anatomical_structure Positron-Emission Tomography Endophenotype Cohort Female Neurology (clinical) Menopause Radiopharmaceuticals medicine.symptom Alzheimer's disease business Biomarkers 030217 neurology & neurosurgery Sex characteristics |
| Zdroj: | Neurology. 89:1382-1390 |
| ISSN: | 1526-632X 0028-3878 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|