Reproductive risk factors for Alzheimer's disease dementia and pathology

阿尔茨海默氏病痴呆的生殖危险因素和病理学

• 批准号: 9250532
• 负责人: Michelle M Mielke
• 金额: $ 397.5万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9250532
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Attention; Bilateral oophorectomy; Brain; Brain Pathology; Brain imaging; Cardiovascular Diseases; Child; Clinic; Clinical; Clinical Trials; Cognition; Cognitive; Comorbidity; Confounding Factors (Epidemiology); Data; Dementia; Development; Diagnosis; Dose; Enrollment; Epidemiology; Exposure to; Future; Genotype; Goals; Gonadal Steroid Hormones; Gynecologic Surgical Procedures; High Prevalence; Hormonal; Hormonal Change; Impaired cognition; Individual; Infarction; Language; Lesion; Literature; Long-Term Effects; Longevity; Magnetic Resonance Imaging; Measures; Medical; Medical Record Linkage; Memory; Menarche; Menopause; Multimodal Imaging; Nerve Degeneration; Observational Study; Operative Surgical Procedures; Pathology; Performance; Population Study; Positron-Emission Tomography; Pre-Eclampsia; Pregnancy; Premature Menopause; Recording of previous events; Research; Research Infrastructure; Risk; Risk Factors; Severities; Sex Characteristics; Structure; System; Testing; Thick; United States National Institutes of Health; Visuospatial; White Matter Hyperintensity; Woman; aging brain; brain morphology; brain size; brain volume; cerebrovascular; cognitive function; disorder subtype; fluorodeoxyglucose positron emission tomography; gray matter; hormone therapy; imaging study; indexing; men; mild cognitive impairment; neuroimaging; pregnancy disorder; processing speed; reproductive; sex; white matter

PROJECT SUMMARY/ABSTRACT Recent estimates suggest that almost two-thirds of the individuals diagnosed with Alzheimer’s disease [AD] are women. The National Institutes of Health and the Alzheimer’s Association have highlighted the critical need to understand sex differences in the risk factors and clinical progression of AD. Reproductive and hormonal factors may be particularly important for women. Hypertensive pregnancy disorders [HPD] have been associated with subjective cognitive complaints or white matter lesions five to ten years after the HPD, but the long-term effects of HPD on brain structure and cognitive function are unknown. Population-based studies are needed to assess the contribution of HPD and subtype (i.e., preeclampsia) to the risk of cognitive decline, AD, and neuroimaging measures of amyloid-beta [Aβ], neurodegeneration, and cerebrovascular pathologies. Further, observational studies and clinical trials have examined the effects of early menopause (natural or surgically-induced) and hormonal therapy [HT] on the risk of AD and other dementias. However, it is not currently known whether the effects of early menopause, HT use, and their interactions with APOE genotype, are associated with specific type(s) of brain pathology (i.e., Aβ, neurodegeneration, cerebrovascular) because multi-modal imaging studies have not been conducted. The overall aims of this proposal are to elucidate the impact of two hormonally-related sex-specific factors for women, pregnancy (e.g., number of pregnancies, HPD) and menopause (surgically-induced or natural), on the risk of cognitive decline, AD, and neuroimaging measures of Aβ, neurodegeneration, and cerebrovascular pathologies. Because the literature and our preliminary data suggest that risk scores for cardiovascular disease and dementia are less predictive in women compared to men, we also propose to incorporate these sex-specific factors to develop a more predictive risk score of mild cognitive impairment and AD for women. To accomplish our goals, we will utilize two existing infrastructures at the Mayo Clinic: the Mayo Clinic Study of Aging (MCSA; U01 AG006786) and the Rochester Epidemiology Project medical records-linkage system (REP; R01 AG034676). Using the REP, we will newly abstract information on pregnancy and menopause for 2,370 women enrolled in the MCSA. Because few studies assessing pregnancy and menopause have also adjusted for putative confounding variables, we will also abstract this data using the REP to determine whether these sex-specific conditions are independent predictors of cognitive decline, AD, and neuroimaging measures of specific brain pathologies. Successful completion of these aims will be a key step towards understanding whether these sex-specific factors are associated with the risk of AD in women, to understanding whether these factors are related to a specific type of brain pathology (i.e., Aβ, neurodegeneration, cerebrovascular), and to developing a better risk score for predicting cognitive impairment, dementia, and specific brain changes in women.

项目总结/文摘