Mielke, Michelle M

AbstractIntroductionWe examined and compared plasma phospho‐tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ.MethodsParticipants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181.ResultsPlasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE).DiscussionPlasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ.

Purpose This cohort study was established to investigate the effects of unilateral and bilateral oophorectomy on the ageing processes in women. Participants We used the records-linkage system of the Rochester Epidemiology Project (REP, http://www.rochesterproject.org ) to identify 570 women who underwent unilateral oophorectomy and 1653 women who underwent bilateral oophorectomy in Olmsted County, Minnesota from 1988 through 2007 (20 years). Each woman was matched by age (±1 year) to a population-based referent woman who had not undergone any oophorectomy (570 referent women) or bilateral oophorectomy (1653 referent women). These four cohorts are being followed to assess morbidity and mortality and to study imaging and biological markers related to ageing. Findings to date An extensive medical record abstraction using the REP has been completed for each woman to obtain demographic, reproductive and adult life characteristics and extensive clinical information about the surgical procedure and subsequent oestrogen replacement therapy (or other sex steroid therapy). The cohorts have been used to date to study the accumulation of multiple chronic conditions following bilateral oophorectomy in women with or without chronic conditions at the time of the oophorectomy (or index date). From the cohorts, we have also derived a sample of 128 pairs of women for a case–control study linking adverse childhood or adult experiences to the risk of bilateral oophorectomy. Future plans We hypothesise that the abrupt hormonal changes caused by bilateral oophorectomy in younger women have a major effect on the ageing processes across the full body. Therefore, we plan to investigate the risk of a wide range of chronic conditions following bilateral oophorectomy. Specific studies are underway for kidney diseases, psychiatric diseases and neurological diseases. In addition, we plan to invite a subsample of women from the bilateral oophorectomy cohort to participate in an in-person study involving brain imaging and the collection of biomarkers.