Neurobiology of Aging
Volume 30, Issue 8 , Pages 1184-1191 , August 2009

Number of children is associated with neuropathology of Alzheimer's disease in women

  • Michal Schnaider Beeri

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Corresponding Author InformationCorresponding author at: Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy Place, Box 1230, New York, NY 10029, United States. Tel.: +1 212 6598807; fax: +1 212 6595626.
    • ,
  • Michael Rapp

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Department of Psychiatry, Campus Charite Mitte, Humboldt University, Berlin, Germany
    • ,
  • James Schmeidler

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Department of Biostatistics, One Gustave Levy L. Place, New York, NY 10029, United States
    • ,
  • Abraham Reichenberg

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Department of Psychological Medicine, Institute of Psychiatry, King's College, London, United Kingdom
    • ,
  • Dushyant P. Purohit

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Department of Pathology, One Gustave Levy L. Place, New York, NY 10029, United States
    • ,
  • Daniel P. Perl

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Department of Pathology, One Gustave Levy L. Place, New York, NY 10029, United States
    • ,
  • Hillel T. Grossman

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Bronx VA Medical Center, 130 Kingsbridge Road, Bronx, NY 10468, United States
    • ,
  • Isak Prohovnik

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Bronx VA Medical Center, 130 Kingsbridge Road, Bronx, NY 10468, United States
    • ,
  • Vahram Haroutunian

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Bronx VA Medical Center, 130 Kingsbridge Road, Bronx, NY 10468, United States
    • Both authors contributed equally to the study.
    • ,
  • Jeremy M. Silverman

      Affiliations

    • The Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy L. Place, New York, NY 10029, United States
    • Both authors contributed equally to the study.

Received 13 February 2007 ,Revised 16 October 2007 ,Accepted 8 November 2007.

References 

  1. Andel R, Vigen C, Mack WJ, Clark LJ, Gatz M. The effect of education and occupational complexity on rate of cognitive decline in Alzheimer's patients. J. Int. Neuropsychol. Soc. 2006;12(1):147–152
  2. Andersen K, Launer LJ, Dewey ME, Letenneur L, Ott A, Copeland JR, et al. Gender differences in the incidence of AD and vascular dementia: the EURODEM studies, EURODEM Incidence Research Group. Neurology. 1999;53(9):1992–1997
  3. Asbury ET, Fritts ME, Horton JE, Isaac WL. Progesterone facilitates the acquisition of avoidance learning and protects against subcortical neuronal death following prefrontal cortex ablation in the rat. Behav. Brain Res. 1998;97(1/2):99–106
  4. Atwood CS, Meethal SV, Liu T, Wilson AC, Gallego M, Smith MA, et al. Dysregulation of the hypothalamic–pituitary–gonadal axis with menopause and andropause promotes neurodegenerative senescence. J. Neuropathol. Exp. Neurol. 2005;64(2):93–103
  5. Beeri MS, Rapp M, Silverman JM, Schmeidler J, Grossman HT, Fallon JT, et al. Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers. Neurology. 2006;66(9):1399–1404
  6. Bernstein L, Pike MC, Ross RK, Judd HL, Brown JB, Henderson BE. Estrogen and sex hormone-binding globulin levels in nulliparous and parous women. J. Natl. Cancer Inst. 1985;74(4):741–745
  7. Bowen RL, Isley JP, Atkinson RL. An association of elevated serum gonadotropin concentrations and Alzheimer disease?. J. Neuroendocrinol. 2000;12(4):351–354
  8. Bowen RL, Smith MA, Harris PL, Kubat Z, Martins RN, Castellani RJ, et al. Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology. J. Neurosci. Res. 2002;70(3):514–518
  9. Bowen RL, Atwood CS, Perry G, Smith MA. Mechanisms involved in gender differences in Alzheimer's disease: the role of luteinizing and follicle stimulation hormones. In:  Legato ML editors. Principles of Gender Specific Medicine. San Diego: Academic Press; 2004;p. 1234–1237
  10. Bowen RL, Verdile G, Liu T, Parlow AF, Perry G, Smith MA, et al. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition. J. Biol. Chem. 2004;279(19):20539–20545
  11. Braak H, Braak E. Evolution of the neuropathology of Alzheimer's disease. Acta Neurol. Scand. Suppl. 1996;1653–1712
  12. Cervantes M, Gonzalez-Vidal MD, Ruelas R, Escobar A, Morali G. Neuroprotective effects of progesterone on damage elicited by acute global cerebral ischemia in neurons of the caudate nucleus. Arch. Med. Res. 2002;33(1):6–14
  13. Cimarosti H, Siqueira IR, Zamin LL, Nassif M, Balk R, Frozza R, et al. Neuroprotection and protein damage prevention by estradiol replacement in rat hippocampal slices exposed to oxygen-glucose deprivation. Neurochem. Res. 2005;30(4):583–589
  14. Clapp JF, Capeless E. Cardiovascular function before, during, and after the first and subsequent pregnancies. Am. J. Cardiol. 1997;80(11):1469–1473
  15. Coffey CE, Lucke JF, Saxton JA, Ratcliff G, Unitas LJ, Billig B, et al. Sex differences in brain aging: a quantitative magnetic resonance imaging study. Arch. Neurol. 1998;55(2):169–179
  16. Colucci M, Cammarata S, Assini A, Croce R, Clerici F, Novello C, et al. The number of pregnancies is a risk factor for Alzheimer's disease. Eur. J. Neurol. 2006;13(12):1374–1377
  17. Corbo RM, Gambina G, Ulizzi L, Monini P, Broggio E, Rosano A, et al. Combined effect of apolipoprotein e genotype and past fertility on age at onset of alzheimer's disease in women. Dement. Geriatr. Cogn. Disord. 2007;24(2):82–85
  18. D’Elio MA, Ness RB, Matthews KA, Kuller LH. Are life stress and social support related to parity in women?. Behav. Med. 1997;23(2):87–94
  19. Dodoo FN. Female education, age, parity, and reproduction cessation in Ghana. Soc. Biol. 1992;39(1–2):102–108
  20. Du B, Ohmichi M, Takahashi K, Kawagoe J, Ohshima C, Igarashi H, et al. Both estrogen and raloxifene protect against beta-amyloid-induced neurotoxicity in estrogen receptor alpha-transfected PC12 cells by activation of telomerase activity via Akt cascade. J. Endocrinol. 2004;183(3):605–615
  21. Fahraeus L, Larsson-Cohn U, Wallentin L. Plasma lipoproteins including high-density lipoprotein subfractions during normal pregnancy. Obstet. Gynecol. 1985;66(4):468–472
  22. Fillenbaum GG, Peterson B, Morris JC. Estimating the validity of the clinical dementia rating scale: the CERAD experience. Consortium to establish a registry for Alzheimer's disease. Aging (Milano). 1996;8(6):379–385
  23. Garcia-Segura LM, Azcoitia I, DonCarlos LL. Neuroprotection by estradiol. Prog. Neurobiol. 2001;63(1):29–60
  24. Genazzani AR, Gastaldi M, Bidzinska B, Mercuri N, Genazzani AD, Nappi RE, et al. The brain as a target organ of gonadal steroids. Psychoneuroendocrinology. 1992;17(4):385–390
  25. Gleason CE, Cholerton B, Carlsson CM, Johnson SC, Asthana S. Neuroprotective effects of female sex steroids in humans: current controversies and future directions. Cell Mol. Life Sci. 2005;62(3):299–312
  26. Goodman Y, Bruce AJ, Cheng B, Mattson MP. Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J. Neurochem. 1996;66(5):1836–1844
  27. Hankinson SE, Colditz GA, Hunter DJ, Manson JE, Willett WC, Stampfer MJ, et al. Reproductive factors and family history of breast cancer in relation to plasma estrogen and prolactin levels in postmenopausal women in the Nurses’ Health Study (United States). Cancer Causes Control. 1995;6(3):217–224
  28. Hardy R, Lawlor DA, Black S, Wadsworth ME, Kuh D. Number of children and coronary heart disease risk factors in men and women from a British birth cohort. BJOG. 2007;114(6):721–730
  29. Haroutunian V, Perl DP, Purohit DP, Marin D, Khan K, Lantz M, et al. Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch. Neurol. 1998;55(9):1185–1191
  30. Haroutunian V, Purohit DP, Perl DP, Marin D, Khan K, Lantz M, et al. Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease. Arch. Neurol. 1999;56(6):713–718
  31. Haroutunian V, Serby M, Purohit DP, Perl DP, Marin D, Lantz M, et al. Contribution of Lewy body inclusions to dementia in patients with and without Alzheimer disease neuropathological conditions. Arch. Neurol. 2000;57(8):1145–1150
  32. Honig LS, Kukull W, Mayeux R. Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center. Neurology. 2005;64(3):494–500
  33. Hy LX, Keller DM. Prevalence of AD among whites: a summary by levels of severity. Neurology. 2000;55(2):198–204
  34. Kritz-Silverstein D, Barrett-Connor E, Wingard DL. The relationship between multiparity and lipoprotein levels in older women. J. Clin. Epidemiol. 1992;45(7):761–767
  35. Kritz-Silverstein D, Barrett-Connor E, Wingard DL, Friedlander NJ. Relation of pregnancy history to insulin levels in older, non-diabetic women. Am. J. Epidemiol. 1994;140(4):375–382
  36. Lahmann PH, Lissner L, Gullberg B, Berglund G. Socio-demographic factors associated with long-term weight gain, current body fatness and central adiposity in Swedish women. Int. J. Obes. Relat. Metab. Disord. 2000;24(6):685–694
  37. Lao XQ, Thomas GN, Jiang CQ, Zhang WS, Yin P, Schooling M, et al. Parity and the metabolic syndrome in older Chinese women: the Guangzhou Biobank Cohort Study. Clin. Endocrinol. (Oxf.). 2006;65(4):460–469
  38. Lawlor DA, Emberson JR, Ebrahim S, Whincup PH, Wannamethee SG, Walker M, 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. Circulation. 2003;107(9):1260–1264
  39. Lewis CE, Funkhouser E, Raczynski JM, Sidney S, Bild DE, Howard BV. Adverse effect of pregnancy on high density lipoprotein (HDL) cholesterol in young adult women. The CARDIA Study. Coronary artery risk development in young adults. Am. J. Epidemiol. 1996;144(3):247–254
  40. Luchsinger JA, Mayeux R. Cardiovascular risk factors and Alzheimer's disease. Curr. Atheroscler. Rep. 2004;6(4):261–266
  41. Marin R, Guerra B, Hernandez-Jimenez JG, Kang XL, Fraser JD, Lopez FJ, et al. Estradiol prevents amyloid-beta peptide-induced cell death in a cholinergic cell line via modulation of a classical estrogen receptor. Neuroscience. 2003;121(4):917–926
  42. McLay RN, Maki PM, Lyketsos CG. Nulliparity and late menopause are associated with decreased cognitive decline. J. Neuropsychiatry Clin. Neurosci. 2003;15(2):161–167
  43. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The consortium to establish a registry for Alzheimer's disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41(4):479–486
  44. Morris JC, Ernesto C, Schafer K, Coats M, Leon S, Sano M, et al. Clinical dementia rating training and reliability in multicenter studies: the Alzheimer's disease Cooperative Study experience. Neurology. 1997;48(6):1508–1510
  45. Morrison JH, Brinton RD, Schmidt PJ, Gore AC. Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J. Neurosci. 2006;26(41):10332–10348
  46. Ness RB, Harris T, Cobb J, Flegal KM, Kelsey JL, Balanger A, et al. Number of pregnancies and the subsequent risk of cardiovascular disease. N. Engl. J. Med. 1993;328(21):1528–1533
  47. Nicholson WK, Asao K, Brancati F, Coresh J, Pankow JS, Powe NR. Parity and risk of type 2 diabetes: the atherosclerosis risk in Communities Study. Diabetes Care. 2006;29(11):2349–2354
  48. O’donoghue K, Choolani M, Chan J, de la FJ, Kumar S, Campagnoli C, et al. Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis. Mol. Hum. Reprod. 2003;9(8):497–502
  49. Pike CJ. Estrogen modulates neuronal Bcl-xL expression and beta-amyloid-induced apoptosis: relevance to Alzheimer's disease. J. Neurochem. 1999;72(4):1552–1563
  50. Ptok U, Barkow K, Heun R. Fertility and number of children in patients with Alzheimer's disease. Arch. Womens Ment. Health. 2002;5(2):83–86
  51. Qureshi AI, Giles WH, Croft JB, Stern BJ. Number of pregnancies and risk for stroke and stroke subtypes. Arch. Neurol. 1997;54(2):203–206
  52. Rao CV, Lei ZM. The past, present and future of nongonadal LH/hCG actions in reproductive biology and medicine. Mol. Cell Endocrinol. 2007;269(1–2):2–8
  53. Sadaniantz A, Saint LL, Parisi AF. Long-term effects of multiple pregnancies on cardiac dimensions and systolic and diastolic function. Am. J. Obstet. Gynecol. 1996;174(3):1061–1064
  54. Scarmeas N, Albert SM, Manly JJ, Stern Y. Education and rates of cognitive decline in incident Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry. 2006;77(3):308–316
  55. Serby M, Brickman AM, Haroutunian V, Purohit DP, Marin D, Lantz M, et al. Cognitive burden and excess Lewy-body pathology in the Lewy-body variant of Alzheimer disease. Am. J. Geriatr. Psychiatry. 2003;11(3):371–374
  56. Short RA, Bowen RL, O’Brien PC, Graff-Radford NR. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo Clin. Proc. 2001;76(9):906–909
  57. Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: women's health initiative memory study. JAMA. 2004;291(24):2947–2958
  58. Singh M. Progesterone-induced neuroprotection. Endocrine. 2006;29(2):271–274
  59. Smith YR, Minoshima S, Kuhl DE, Zubieta JK. Effects of long-term hormone therapy on cholinergic synaptic concentrations in healthy postmenopausal women. J. Clin. Endocrinol. Metab. 2001;86(2):679–684
  60. Sobow T, Kloszewska I. Parity, number of pregnancies, and the age of onset of Alzheimer's disease. J. Neuropsychiatry Clin. Neurosci. 2004;16(1):120–121
  61. Tang YP, Haslam SZ, Conrad SE, Sisk CL. Estrogen increases brain expression of the mRNA encoding transthyretin, an amyloid beta scavenger protein. J. Alzheimers Dis. 2004;6(4):413–420
  62. Toescu V, Nuttall SL, Martin U, Kendall MJ, Dunne F. Oxidative stress and normal pregnancy. Clin. Endocrinol. (Oxf). 2002;57(5):609–613
  63. Vural P, Akgul C, Canbaz M. Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women. Pharmacol. Res. 2006;54(4):298–302
  64. Webber KM, Casadesus G, Atwood CS, Bowen RL, Perry G, Smith MA. Gonadotropins: a cohesive gender-based etiology of Alzheimer disease. Mol. Cell Endocrinol. 2007;260–262:271–275
  65. Webber KM, Casadesus G, Marlatt MW, Perry G, Hamlin CR, Atwood CS, et al. Estrogen bows to a new master: the role of gonadotropins in Alzheimer pathogenesis. Ann. N.Y. Acad. Sci. 2005;1052:201–209
  66. Webber KM, Casadesus G, Perry G, Atwood CS, Bowen R, Smith MA. Gender differences in Alzheimer disease: the role of luteinizing hormone in disease pathogenesis. Alzheimer Dis. Assoc. Disord. 2005;19(2):95–99
  67. Wilson RS, Arnold SE, Schneider JA, Kelly JF, Tang Y, Bennett DA. Chronic psychological distress and risk of Alzheimer's disease in old age. Neuroepidemiology. 2006;27(3):143–153
  68. Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, et al. Brain estrogen deficiency accelerates Abeta plaque formation in an Alzheimer's disease animal model. Proc. Natl. Acad. Sci. U.S.A. 2005;102(52):19198–19203
  69. Zhang Y, Champagne N, Beitel LK, Goodyer CG, Trifiro M, LeBlanc A. Estrogen and androgen protection of human neurons against intracellular amyloid beta1-42 toxicity through heat shock protein 70. J. Neurosci. 2004;24(23):5315–5321

PII: S0197-4580(07)00438-1

doi: 10.1016/j.neurobiolaging.2007.11.011

Neurobiology of Aging
Volume 30, Issue 8 , Pages 1184-1191 , August 2009

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