title: Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women.
abstract: OBJECTIVE
  To determine the association between age at surgical menopause and both cognitive decline and Alzheimer disease (AD) pathology in 2 longitudinal cohorts.
  
  
  METHODS
  Female subjects from 2 longitudinal studies of cognitive decline (Religious Orders Study and Rush Memory and Aging Project) were included (total n = 1,884). The primary analysis examined the association between age at surgical menopause and decline in a global cognition score. Secondary analyses examined additional outcomes: 1) decline in 5 cognitive subdomains and 2) a global measure of the burden of AD pathology. In exploratory analyses, we examined the effect of hormone replacement therapy (HRT). We adjusted all models for age, education, smoking, and cohort and stratified by surgical vs natural menopause.
  
  
  RESULTS
  For the 32% of subjects with surgical menopause, earlier age at menopause was associated with faster decline in global cognition (p = 0.0007), specifically episodic memory (p = 0.0003) and semantic memory (p = 0.002). Earlier age at menopause was also associated with increased AD neuropathology (p = 0.038), in particular neuritic plaques (p = 0.013). HRT use for at least 10 years, when administered within a 5-year perimenopausal window, was associated with decreased decline in global cognition. No associations were seen in women who had natural menopause.
  
  
  CONCLUSIONS
  Early age at surgical menopause was associated with cognitive decline and AD neuropathology. Ongoing studies should clarify the potential effect of HRT on this relationship.
authors: From the Program in Translational NeuroPsychiatric Genomics (R.B., E.S., L.B.C., P.L.D.), Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital; Harvard Medical School (R.B., L.B.C., P.L.D.), Boston, MA; and the Departments of Neurological Sciences (L.L.B.) and Neuropathology (J.A.S., D.A.B.), Rush University Medical Center, Chicago, IL.
authors: Riley
authors: R
authors: Bove
authors: Elizabeth
authors: E
authors: Secor
authors: Lori B
authors: LB
authors: Chibnik
authors: Lisa L
authors: LL
authors: Barnes
authors: Julie A
authors: JA
authors: Schneider
authors: David A
authors: DA
authors: Bennett
authors: Philip L
authors: PL
authors: De Jager
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006306:Health Surveys; D020249:Hormone Replacement Therapy / Q000706:statistics & numerical data*; D006801:Humans; D008137:Longitudinal Studies; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D061212:Memory, Episodic; D008593:Menopause / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000209:etiology / Q000473:pathology; D016037:Single-Blind Method; D016896:Treatment Outcome