Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease

doi:10.1212/WNL.0000000000006000

. 2018 Aug 14;91(7):e643-e651.

doi: 10.1212/WNL.0000000000006000. Epub 2018 Jul 18.

Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease

Hyesue Jang¹, Jong Bin Bae¹, Efthimios Dardiotis¹, Nikolaos Scarmeas¹, Perminder S Sachdev¹, Darren M Lipnicki¹, Ji Won Han¹, Tae Hui Kim¹, Kyung Phil Kwak¹, Bong Jo Kim¹, Shin Gyeom Kim¹, Jeong Lan Kim¹, Seok Woo Moon¹, Joon Hyuk Park¹, Seung-Ho Ryu¹, Jong Chul Youn¹, Dong Young Lee¹, Dong Woo Lee¹, Seok Bum Lee¹, Jung Jae Lee¹, Jin Hyeong Jhoo¹, Mary Yannakoulia¹, Mary H Kosmidis¹, Giorgos M Hadjigeorgiou¹, Paraskevi Sakka¹, Ki Woong Kim²

Affiliations

¹ 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.
² 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. kwkimmd@snu.ac.kr.

PMID: 30021919
PMCID: PMC9811944
DOI: 10.1212/WNL.0000000000006000

Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease

Hyesue Jang et al. Neurology. 2018.

. 2018 Aug 14;91(7):e643-e651.

doi: 10.1212/WNL.0000000000006000. Epub 2018 Jul 18.

Authors

Affiliations

¹ 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.
² 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. kwkimmd@snu.ac.kr.

PMID: 30021919
PMCID: PMC9811944
DOI: 10.1212/WNL.0000000000006000

Abstract

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 worse MMSE 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.

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Figures

**Figure. Effects of completed and incomplete pregnancies on MMSE scores of women without dementia in late life**
Analysis of variance with the Tukey post hoc comparisons adjusted for cohort; age; level of education; socioeconomic status; employment; history of diabetes mellitus, hypertension, and hyperlipidemia; Geriatric Depression Scale Short Form score; years of reproductive period; and age at menopause. Error bars indicate standard error. MMSE = Mini-Mental State Examination.

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References

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[1] Mielke MM, Vemuri P, Rocca WA. Clinical epidemiology of Alzheimer's disease: assessing sex and gender differences. Clin Epidemiol 2014;6:37–48. - PMC - PubMed

[2] Mielke MM, Vemuri P, Rocca WA. Clinical epidemiology of Alzheimer's disease: assessing sex and gender differences. Clin Epidemiol 2014;6:37–48. - PMC - PubMed

[3] Ptok U, Barkow K, Heun R. Fertility and number of children in patients with Alzheimer's disease. Arch Womens Ment Health 2002;5:83–86. - PubMed

[4] Ptok U, Barkow K, Heun R. Fertility and number of children in patients with Alzheimer's disease. Arch Womens Ment Health 2002;5:83–86. - PubMed

[5] Colucci M, Cammarata S, Assini A, et al. . The number of pregnancies is a risk factor for Alzheimer's disease. Eur J Neurol 2006;13:1374–1377. - PubMed

[6] Colucci M, Cammarata S, Assini A, et al. . The number of pregnancies is a risk factor for Alzheimer's disease. Eur J Neurol 2006;13:1374–1377. - PubMed

[7] Beeri MS, Rapp M, Schmeidler J, et al. . Number of children is associated with neuropathology of Alzheimer's disease in women. Neurobiol Aging 2009;30:1184–1191. - PMC - PubMed

[8] Beeri MS, Rapp M, Schmeidler J, et al. . Number of children is associated with neuropathology of Alzheimer's disease in women. Neurobiol Aging 2009;30:1184–1191. - PMC - PubMed

[9] Inagaki T, Gautreaux C, Luine V. Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas. Horm Behav 2010;58:415–426. - PMC - PubMed

[10] Inagaki T, Gautreaux C, Luine V. Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas. Horm Behav 2010;58:415–426. - PMC - PubMed

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Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease

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Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease

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