Premenopausal bilateral oophorectomy and Alzheimer's disease imaging biomarkers later in life

Introduction: Premenopausal bilateral oophorectomy (PBO) before the age of 46 years is associated with an increased risk of dementia. We investigated the long-term effects of PBO performed before age 50 years on amyloid beta (Aβ), tau, and neurodegeneration imaging biomarkers of Alzheimer's disease (AD).

Methods: Mayo Clinic Cohort Study of Oophorectomy and Aging-2 participants were divided into early PBO (< 46 years; n = 61), and late PBO (46-49 years; n = 51) groups and were compared to referent women who did not undergo PBO (n = 119).

Results: Early PBO was associated with thinner entorhinal cortex (p = 0.014), higher tau load at higher levels of Aβ load (Pp = 0.005), higher Aβ load (p = 0.026), and smaller temporal lobe cortical thickness (p = 0.022), only at older ages compared to the referent group.

Discussion: PBO before the age of 46 years is associated with entorhinal cortex thinning, elevated tau at higher Aβ levels, along with an AD-like pattern of atrophy at older ages.

Clinical trials registration: NCT03821857 sex-specific effects of endocrine disruption on aging and AD.

Highlights: Premenopausal bilateral oophorectomy (PBO) before the ages of 46 (early PBO) years and ages 46 to 49 (late PBO) years was studied. Early PBO was associated with reduced entorhinal cortex thickness later in life. Early PBO was associated with greater amyloid beta (Aβ) load at older ages. Early PBO was associated with greater Alzheimer's disease pattern of atrophy at older ages. Early PBO was associated with higher tau load at higher Aβ levels.