ects of completed and incomplete pregnancies on the risk of Alzheimer disease

Objective To investigate the effects of completed pregnancy with childbirth and incomplete pregnancy without childbirth on the late-life cognition and the risk of Alzheimer disease (AD) in women. Methods Using the pooled data of 3,549 women provided by 2 population-based cohort studies, we conducted logistic regression analyses to examine retrospectively the associations of completed and incomplete pregnancy with the risks of mild cognitive impairment and AD. For women without dementia, we also conducted analyses of covariance to examine the associations of completed and incomplete pregnancy with Mini-Mental State Examination (MMSE) score. Results Grand multiparous women who experienced ≥5 completed pregnancies showed an ≈1.7-fold higher risk of AD than those who experienced 1 to 4 completed pregnancies (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.04–2.72), while those who had incomplete pregnancies showed half the level of AD risk compared with those who never experienced an incomplete pregnancy (OR 0.43, 95% CI 0.24–0.76 for 1 incomplete pregnancy; OR 0.56, 95% CI 0.34–0.92 for ≥2 incomplete pregnancies). In women without dementia, the grand multiparous had worseMMSE scores than those with 1 to 4 completed pregnancies (p < 0.001), while those who experienced ≥1 incomplete pregnancies had better MMSE scores than those who never experienced an incomplete pregnancy (p = 0.008). Conclusions Grand multiparity was associated with high risk of AD, while incomplete pregnancy was associated with low risk of AD in late life. *These authors contributed equally to this work. From the Department of Brain and Cognitive Sciences (H.J., K.W.K.), Seoul National University College of Natural Sciences; Department of Psychiatry (J.B.B., J.W.H., D.Y.L., K.W.K.), Seoul National University, College of Medicine; Department of Neuropsychiatry (J.B.B., J.W.H., K.W.K.), Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Neurology (E.D.), Faculty of Medicine, University of Thessaly, Larissa; Department of Social Medicine, Psychiatry and Neurology (N.S.), National and Kapodistrian University of Athens, Greece; Department of Neurology (N.S.), Columbia University, New York, NY; Centre for Healthy Brain Ageing (P.S.S., D.M.L.) and Dementia Collaborative Research Centre (P.S.S.), University of New South Wales, Sydney, Australia; Department of Psychiatry (T.H.K.), Yonsei University Wonju Severance Christian Hospital; Department of Psychiatry (K.P.K.), Dongguk University Gyeongju Hospital; Department of Psychiatry (B.J.K.), Gyeongsang National University, School of Medicine, Jinju; Department of Neuropsychiatry (S.G.K.), Soonchunhyang University Bucheon Hospital; Department of Psychiatry (J.L.K.), School of Medicine, Chungnam National University, Daejeon; Department of Psychiatry (S.W.M.), School of Medicine, Konkuk University and Konkuk University Chungju Hospital; Department of Neuropsychiatry (J.H.P.), Jeju National University Hospital; Department of Psychiatry, School of Medicine (S.-H.R.), Konkuk University and Konkuk University Medical Center, Seoul; Department of Neuropsychiatry (J.C.Y.), Kyunggi Provincial Hospital for the Elderly, Yongin; Department of Neuropsychiatry (D.Y.L.), Seoul National University Hospital; Department of Neuropsychiatry (D.W.L.), Inje University Sanggye Paik Hospital, Seoul; Department of Psychiatry (S.B.L., J.J.L.), Dankook University Hospital, Cheonan; Department of Psychiatry (J.H.J.), Kangwon National University, School of Medicine, Chuncheon, South Korea; Department of Nutrition and Dietetics (M.Y.), Harokopio University, Athens; Laboratory of Cognitive Neuroscience (M.H.K.), School of Psychology, Aristotle University of Thessaloniki; School of Medicine (G.M.H.), University of Thessaly, Larissa; Athens Association of Alzheimer’s Disease and Related Disorders (P.S.), Marousi, Greece; and Department of Neurology (G.M.H), Medical School, University of Cyprus, Nicosia, Cyprus. Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. Copyright © 2018 American Academy of Neurology e1 Copyright a 2018 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Published Ahead of Print on July 18, 2018 as 10.1212/WNL.0000000000006000

[1]  M. Glymour,et al.  Contribution of Socioeconomic Status at 3 Life-Course Periods to Late-Life Memory Function and Decline: Early and Late Predictors of Dementia Risk , 2017, American journal of epidemiology.

[2]  Xuerui Tan,et al.  Association of Female Reproductive Factors with Hypertension, Diabetes and LQTc in Chinese Women , 2017, Scientific Reports.

[3]  Junfen Lin,et al.  Reproductive history and risk of cognitive impairment in elderly women: a cross-sectional study in eastern China. , 2015, Journal of Alzheimer's disease : JAD.

[4]  N. Scarmeas,et al.  The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD): Rationale, Study Design, and Cohort Description , 2014, Neuroepidemiology.

[5]  S. Swan,et al.  Differences in ovarian hormones in relation to parity and time since last birth. , 2014, Fertility and sterility.

[6]  P. Vemuri,et al.  Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences , 2014, Clinical epidemiology.

[7]  Molly Fox,et al.  Cumulative estrogen exposure, number of menstrual cycles, and Alzheimer's risk in a cohort of British women , 2013, Psychoneuroendocrinology.

[8]  M. Schumacher,et al.  Progesterone Protective Effects in Neurodegeneration and Neuroinflammation , 2013, Journal of neuroendocrinology.

[9]  D. Shapiro,et al.  Fertility Transition in Sub-Saharan Africa: Falling and Stalling , 2013 .

[10]  Kaarin J Anstey,et al.  COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups , 2013, Alzheimer's & Dementia.

[11]  E. Sinforiani,et al.  Reproductive life events and Alzheimer’s disease in Italian women: a retrospective study , 2012, Neuropsychiatric disease and treatment.

[12]  Peter P. Zandi,et al.  Hormone therapy and Alzheimer disease dementia , 2012, Neurology.

[13]  L. Galea,et al.  Endocrine substrates of cognitive and affective changes during pregnancy and postpartum. , 2012, Behavioral neuroscience.

[14]  L. Galea,et al.  Influence of different estrogens on neuroplasticity and cognition in the hippocampus. , 2010, Biochimica et biophysica acta.

[15]  V. Luine,et al.  Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas , 2010, Hormones and Behavior.

[16]  D. Perl,et al.  Number of children is associated with neuropathology of Alzheimer's disease in women , 2009, Neurobiology of Aging.

[17]  L. Rubin,et al.  Effects of menstrual cycle phase and oral contraceptive use on verbal memory , 2008, Hormones and Behavior.

[18]  L. Galea,et al.  Adult hippocampal cell proliferation is suppressed with estrogen withdrawal after a hormone-simulated pregnancy , 2008, Hormones and Behavior.

[19]  Jorge Ghiso,et al.  Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats , 2008, Hormones and Behavior.

[20]  J. Park.  An overview of Korean longitudinal study on health and aging , 2007 .

[21]  P. Peeters,et al.  Lifetime cumulative number of menstrual cycles and serum sex hormone levels in postmenopausal women , 2007, Breast Cancer Research and Treatment.

[22]  F. Clerici,et al.  The number of pregnancies is a risk factor for Alzheimer's disease , 2006, European journal of neurology.

[23]  J. Pankow,et al.  Parity and Risk of Type 2 Diabetes , 2006, Diabetes Care.

[24]  L. Galea,et al.  High level estradiol impairs and low level estradiol facilitates non-spatial working memory , 2004, Behavioural Brain Research.

[25]  R. Petersen.  Mild cognitive impairment as a diagnostic entity , 2004, Journal of internal medicine.

[26]  D. Lawlor,et al.  Is the Association Between Parity and Coronary Heart Disease Due to Biological Effects of Pregnancy or Adverse Lifestyle Risk Factors Associated With Child-Rearing?: Findings From the British Women’s Heart and Health Study and the British Regional Heart Study , 2003, Circulation.

[27]  R. Heun,et al.  Fertility and number of children in patients with Alzheimer's disease , 2002, Archives of Women's Mental Health.

[28]  S. Cummings,et al.  Cognitive decline in women in relation to non-protein-bound oestradiol concentrations , 2000, The Lancet.

[29]  R. Sapolsky,et al.  Glucocorticoids, stress, and their adverse neurological effects: relevance to aging , 1999, Experimental Gerontology.

[30]  R. Berkowitz,et al.  Perinatal outcome in grand and great-grand multiparity: effects of parity on obstetric risk factors. , 1999, American journal of obstetrics and gynecology.

[31]  J. Overstreet,et al.  Relationship of serum estradiol and progesterone concentrations to the excretion profiles of their major urinary metabolites as measured by enzyme immunoassay and radioimmunoassay. , 1991, Clinical chemistry.

[32]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[33]  H. Ruder,et al.  Estrone sulfate, estrone, estradiol and estriol plasma levels in human pregnancy. , 1972, The Journal of clinical endocrinology and metabolism.

[34]  C. Hobel,et al.  Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy. , 1972, American journal of obstetrics and gynecology.

[35]  Molly Fox,et al.  Maternal breastfeeding history and Alzheimer's disease risk. , 2013, Journal of Alzheimer's disease : JAD.

[36]  R. Prentice,et al.  The effects of postmenopausal hormone therapy on serum estrogen, progesterone, and sex hormone-binding globulin levels in healthy postmenopausal women , 2010, Menopause.

[37]  Leslie Carol Botha.  Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women , 2003 .

[38]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.