title: Age at menopause and duration of reproductive period in association with dementia and cognitive function: A systematic review and meta-analysis.
abstract: The preponderance of dementia among postmenopausal women compared with same-age men and the female sex hormones neuroprotective properties support a tentative role of their deficiency in the dementia pathogenesis.
  
  
  
  Pairs of independent reviewers screened 12,323 publications derived from a search strategy for MEDLINE to identify articles investigating the association of age at menopause/reproductive period with (i) dementia and (ii) cognitive function; a snowball of eligible articles and reviews was conducted and authors were contacted for additional information. Random-effect models were used for the meta-analysis.
  
  
  
  Age at menopause (13 studies; 19,449 participants) and reproductive period (4 studies; 9916 participants) in the highest categories were not associated with odds of dementia (effect size [ES]: 0.97 [0.78-1.21]) and Alzheimer's disease (ES: 1.06 [0.71-1.58]). Significant heterogeneity was however noted in both analyses (I2: 63.3%, p=0.003 and I2: 72.6%, p=0.01, respectively). Subgroup analyses by outcome assessment, study design, level of adjustment and study quality did not materially change the findings. In 9/13 studies assessing cognitive function, advanced age at menopause/longer reproductive period was significantly associated with better cognitive performance/lower decline. Due to statistical differences, no meta-analysis was possible for cognitive function.
  
  
  
  Existing evidence does not support an association between indices of prolonged exposure to female hormones and lower dementia risk. There are indications, however, for better cognitive performance and delayed cognitive decline, supporting a link between female hormone deficiency and cognitive aging. Current literature limitations, indicated by the heterogeneous study-set, point towards research priorities in this clinically relevant area.
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece. Electronic address: mgeorgakis91@gmail.com.
authors.forename: Marios K
authors.initials: MK
authors.lastname: Georgakis
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece. Electronic address: lenia_91@yahoo.com.
authors.forename: Eleni I
authors.initials: EI
authors.lastname: Kalogirou
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece; Program Medical Neurosciences, Charité-Universitätsmedizin, Berlin, 10117, Germany. Electronic address: diam_ant@hotmail.com.
authors.forename: Andreas-Antonios
authors.initials: AA
authors.lastname: Diamantaras
authors.affiliation: Division of Internal Medicine, Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, H3G 1A4, Canada. Electronic address: stella.daskalopoulou@mcgill.ca.
authors.forename: Stella S
authors.initials: SS
authors.lastname: Daskalopoulou
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. Electronic address: cmunro@jhmi.edu.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Munro
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. Electronic address: kostas@jhmi.edu.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, 751 85, Sweden. Electronic address: alkistis.skalkidou@kbh.uu.se.
authors.forename: Alkistis
authors.initials: A
authors.lastname: Skalkidou
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece. Electronic address: epetrid@med.uoa.gr.
authors.forename: Eleni Th
authors.initials: ET
authors.lastname: Petridou
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D003704:Dementia / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008593:Menopause / Q000378:metabolism / Q000502:physiology*
keywords: Cognition; Cognitive impairment; Dementia; Female hormones; Menopause; Postmenopausal women