Reproductive factors, including parity, may contribute to dementia risk, due to hormonal, physiological, social, and demographic factors. We hypothesized that higher parity would be associated with increased dementia risk.
Materials and Methods:
We utilized data from the Atherosclerosis Risk in Communities (ARIC) community-based cohort study. Participants were recruited in 1987–1989 and followed through 2017. Participants, all born between 1921 and 1945, were from four U.S. communities in Forsyth County, NC; Jackson, MS; Minneapolis, MN; and Washington County, MD. We included all female participants seen at ARIC visit three or five for whom parity and dementia outcomes were available (N = 7,921). The primary exposure was self-reported number of live births. Our primary outcome was dementia, diagnosed via neurocognitive assessments, informant interviews, and expert adjudication. We created Cox proportional hazards models to evaluate the association between parity and incident dementia, adjusting for demographic factors, education level, apolipoprotein E allele status, and vascular risk factors. We tested for interactions by race and birth cohort.
Results:
The adjusted hazard ratio was 0.82 (95% confidence intervals [CI] 0.69–0.99) for dementia in women with 0–1 births and 0.85 (95% CI 0.72–0.99) for women with 5+ births, compared to women with 2 births (reference group). This association was present in women born from 1924 to 1934, but not in women born in 1935 or later (p-interaction <0.001).
Conclusion:
We found an inverted U-shaped association of parity with dementia risk. This effect was modified by birth cohort, suggesting that the association may depend on demographic and sociocultural factors.
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References
1.
World Health Organization. Global Health Estimates: Life Expectancy and Leading Causes of Death and Disability. Available from: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates [Last accessed: March8, 2023].
2.
MillerEC, WilczekA, BelloNA, et al.Pregnancy, preeclampsia and maternal aging: From epidemiology to functional genomics. Ageing Res Rev, 2022; 73:101535; doi: 10.1016/j.arr.2021.101535
3.
RiedelBC, ThompsonPM, BrintonRD. Age, APOE and sex: Triad of risk of Alzheimer's disease. J Steroid Biochem Mol Biol, 2016; 160:134–147; doi: 10.1016/j.jsbmb.2016.03.012
4.
BarnesLL, WilsonRS, SchneiderJA, et al.Gender, cognitive decline, and risk of AD in older persons. Neurology, 2003; 60(11):1777–1781; doi: 10.1212/01.wnl.0000065892.67099.2a
5.
WeberMT, MakiPM, McDermottMP. Cognition and mood in perimenopause: A systematic review and meta-analysis. J Steroid Biochem Mol Biol, 2014; 142:90–98; doi: 10.1016/j.jsbmb.2013.06.001
6.
PetersonA, TomSE. A lifecourse perspective on female sex-specific risk factors for later life cognition. Curr Neurol Neurosci Rep, 2021; 21(9):46; doi: 10.1007/s11910-021-01133-y
7.
BarthC, de LangeAG. Towards an understanding of women's brain aging: the immunology of pregnancy and menopause. Front Neuroendocrinol, 2020; 58:100850; doi: 10.1016/j.yfrne.2020.100850
8.
HaasDM, ParkerCB, MarshDJ, et al.Association of adverse pregnancy outcomes with hypertension 2 to 7 years postpartum. J Am Heart Assoc, 2019; 8(19):e013092; doi: 10.1161/JAHA.119.013092
9.
LeonLJ, McCarthyFP, DirekK, et al.Preeclampsia and cardiovascular disease in a large uk pregnancy cohort of linked electronic health records: A CALIBER Study. Circulation, 2019; 140(13):1050–1060; doi: 10.1161/CIRCULATIONAHA.118.038080
10.
DayanN, KaurA, ElharramM, et al.Impact of preeclampsia on long-term cognitive function. Hypertension, 2018; 72(6):1374–1380; doi: 10.1161/HYPERTENSIONAHA.118.11320
11.
FoxM, BerzuiniC, KnappLA. Cumulative estrogen exposure, number of menstrual cycles, and Alzheimer's risk in a cohort of British women. Psychoneuroendocrinology, 2013; 38(12):2973–2982; doi: 10.1016/j.psyneuen.2013.08.005
12.
ZhouR, LiuHM, ZouLW, et al.Associations of parity with change in global cognition and incident cognitive impairment in older women. Front Aging Neurosci, 2022; 14:864128; doi: 10.3389/fnagi.2022.864128
13.
SchelbaumE, LoughlinL, JettS, et al.Association of reproductive history with brain MRI biomarkers of dementia risk in midlife. Neurology, 2021; 97(23):e2328–e2339; doi: 10.1212/WNL.0000000000012941
14.
PrinceMJ, AcostaD, GuerraM, et al.Reproductive period, endogenous estrogen exposure and dementia incidence among women in Latin America and China: A 10/66 population-based cohort study. PLoS One, 2018; 13(2):e0192889; doi: 10.1371/journal.pone.0192889
15.
XiH, GanJ, LiuS, et al.Reproductive factors and cognitive impairment in natural menopausal women: A cross-sectional study. Front Endocrinol (Lausanne), 2022; 13:893901; doi: 10.3389/fendo.2022.893901
16.
BeeriMS, RappM, SchmeidlerJ, et al.Number of children is associated with neuropathology of Alzheimer's disease in women. Neurobiol Aging, 2009; 30(8):1184–1191, doi:10.1016/j.neurobiolaging.2007.11.011
17.
PtokU, BarkowK, HeunR. Fertility and number of children in patients with Alzheimer's disease. Arch Womens Ment Health, 2002; 5(2):83–86; doi: 10.1007/s00737-002-0142-6
18.
KnopmanDS, GottesmanRF, SharrettAR, et al.Mild cognitive impairment and dementia prevalence: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Alzheimers Dement (Amst), 2016; 2:1–11; doi: 10.1016/j.dadm.2015.12.002
19.
WrightJD, FolsomAR, CoreshJ, et al.The ARIC (Atherosclerosis Risk In Communities) Study: JACC focus seminar 3/8. J Am Coll Cardiol, 2021; 77(23):2939–2959; doi: 10.1016/j.jacc.2021.04.035
20.
The Atherosclerosis Risk in Communities (ARIC) Study: Design and objectives. The ARIC investigators. Am J Epidemiol, 1989; 129(4):687–702.
21.
NorbyFL, ChenLY, SolimanEZ, et al.Association of left ventricular hypertrophy with cognitive decline and dementia risk over 20years: The Atherosclerosis Risk In Communities-Neurocognitive Study (ARIC-NCS). Am Heart J, 2018; 204:58–67; doi: 10.1016/j.ahj.2018.07.007
22.
RawlingsAM, Bandeen-RocheK, GrossAL, et al.Factor structure of the ARIC-NCS neuropsychological battery: An evaluation of invariance across vascular factors and demographic characteristics. Psychol Assess, 2016; 28(12):1674–1683; doi: 10.1037/pas0000293
23.
GottesmanRF, SchneiderAL, ZhouY, et al.Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA, 2017; 317(14):1443–1450; doi: 10.1001/jama.2017.3090
24.
GottesmanRF, AlbertMS, AlonsoA, et al.Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol, 2017; 74(10):1246–1254; doi: 10.1001/jamaneurol.2017.1658
25.
McKhannGM, KnopmanDS, ChertkowH, et al.The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement (Amst), 2011; 7(3):263–269; doi: 10.1016/j.jalz.2011.03.005
26.
AlbertMS, DeKoskyST, DicksonD, et al.The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement (Amst), 2011; 7(3):270–279, doi:10.1016/j.jalz.2011.03.008
27.
Diagnostic and statistical manual of mental disorders: DSM-5™, 5th ed. American Psychiatric Publishing, Inc.: Arlington, VA, US; 2013.
28.
AlonsoA, MosleyTHJr., GottesmanRF, et al.Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: The Atherosclerosis Risk in Communities (ARIC) study. J Neurol Neurosurg Psychiatry, 2009; 80(11):1194–1201; doi: 10.1136/jnnp.2009.176818
29.
SchneiderAL, GottesmanRF, MosleyT, et al.Cognition and incident dementia hospitalization: Results from the atherosclerosis risk in communities study. Neuroepidemiology, 2013; 40(2):117–124; doi: 10.1159/000342308
30.
BaeckeJA, BuremaJ, FrijtersJE. A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr, 1982; 36(5):936–942; doi: 10.1093/ajcn/36.5.936
31.
MedianoMFF, MokY, CoreshJ, et al.Prestroke physical activity and adverse health outcomes after stroke in the Atherosclerosis Risk in Communities Study. Stroke, 2021; 52(6):2086–2095; doi: 10.1161/STROKEAHA.120.032695
32.
MakiPM, HendersonVW. Hormone therapy, dementia, and cognition: The Women's Health Initiative 10 years on. Climacteric, 2012; 15(3):256–262; doi: 10.3109/13697137.2012.660613
33.
BrintonRD, YaoJ, YinF, et al.Perimenopause as a neurological transition state. Nat Rev Endocrinol, 2015; 11(7):393–405; doi: 10.1038/nrendo.2015.82
34.
AppiahD, NwabuoCC, EbongIA, et al.Trends in age at natural menopause and reproductive life span among US women, 1959–2018. JAMA, 2021; 325(13):1328–1330; doi: 10.1001/jama.2021.0278
35.
GilsanzP, LeeC, CorradaMM, et al.Reproductive period and risk of dementia in a diverse cohort of health care members. Neurology, 2019; 92(17):e2005–e2014; doi: 10.1212/WNL.0000000000007326
36.
YooJE, ShinDW, HanK, et al.Female reproductive factors and the risk of dementia: A nationwide cohort study. Eur J Neurol, 2020; 27(8):1448–1458; doi: 10.1111/ene.14315
37.
PawluskiJL, GaleaLA. Hippocampal morphology is differentially affected by reproductive experience in the mother. J Neurobiol, 2006; 66(1):71–81; doi: 10.1002/neu.20194
38.
KinsleyCH, TrainerR, Stafisso-SandozG, et al.Motherhood and the hormones of pregnancy modify concentrations of hippocampal neuronal dendritic spines. Horm Behav, 2006; 49(2):131–142; doi: 10.1016/j.yhbeh.2005.05.017
39.
LiR, CuiJ, JothishankarB, et al.Early reproductive experiences in females make differences in cognitive function later in life. J Alzheimers Dis, 2013; 34(3):589–594; doi: 10.3233/JAD-122101
40.
JungJH, LeeGW, LeeJH, et al.Multiparity, Brain atrophy, and cognitive decline. Front Aging Neurosci, 2020; 12:159; doi: 10.3389/fnagi.2020.00159
41.
ReadSL, GrundyEMD. Fertility history and cognition in later life. J Gerontol B Psychol Sci Soc Sci, 2017; 72(6):1021–1031; doi: 10.1093/geronb/gbw013
42.
FurstenbergFF. Banking on families: How families generate and distribute social capital. J Marriage Fam, 2005; 67:809–821.
43.
ZhouZ, WangP, FangY. Social engagement and its change are associated with dementia risk among chinese older adults: A longitudinal study. Sci Rep, 2018; 8(1):1551; doi: 10.1038/s41598-017-17879-w
44.
GrundyE, ReadS. Social contacts and receipt of help among older people in England: Are there benefits of having more children?. J Gerontol B Psychol Sci Soc Sci, 2012; 67(6):742–754; doi: 10.1093/geronb/gbs082
45.
RossCE, MirowskyJ. Family relationships, social support and subjective life expectancy. J Health Soc Behav, 2002; 43(4):469–489.
46.
KirkwoodTB, RoseMR. Evolution of senescence: Late survival sacrificed for reproduction. Philos Trans R Soc Lond B Biol Sci, 1991; 332(1262):15–24; doi: 10.1098/rstb.1991.0028
47.
DeclercqE, ZephyrinLC. Maternal Mortality in the United States: A Primer [Internet]. New York, USA: The Commonweath Fund; updated December 16, 2020. Available from: https://www.commonwealthfund.org/publications/issue-brief-report/2020/dec/maternal-mortality-united-states-primer [Last accessed: July25, 2023].
48.
Centers for Disease Control and Prevention. Fertility Tables for Birth Cohorts by Color 1973. Available from: https://stacks.cdc.gov/view/cdc/21853 [Last accessed; March 11, 2023].
49.
National Center for Education Statistics. 120 Years of American Education: A Statistical Portrait. Available from: https://nces.ed.gov/pubs93/93442.pdf [Last accessed: March12, 2023].
50.
BeckerGS. A Treatise on the family. Am J Sociol, 1983; 89:468–470.
51.
CreangaAA, BatemanBT, KuklinaEV, et al.Racial and ethnic disparities in severe maternal morbidity: A multistate analysis, 2008–2010. Am J Obstet Gynecol, 2014; 210(5):435 e1–e8; doi: 10.1016/j.ajog.2013.11.039
52.
Gyamfi-BannermanC, PanditaA, MillerEC, et al.Preeclampsia outcomes at delivery and race. J Matern Fetal Neonatal Med, 2020; 33(21):3619–3626; doi: 10.1080/14767058.2019.1581522
53.
GrandiSM, FilionKB, YoonS, et al.Cardiovascular disease-related morbidity and mortality in women with a history of pregnancy complications. Circulation, 2019; 139(8):1069–1079; doi: 10.1161/CIRCULATIONAHA.118.036748
54.
WuP, GulatiM, KwokCS, et al.Preterm delivery and future risk of maternal cardiovascular disease: A systematic review and meta-analysis. J Am Heart Assoc, 2018; 7(2):e007809; doi: 10.1161/JAHA.117.007809
55.
WuP, HaththotuwaR, KwokCS, et al.Preeclampsia and future cardiovascular health: A systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes, 2017; 10(2):e003497; doi: 10.1161/CIRCOUTCOMES.116.003497
56.
MillerEC, BelloNA, DavisR, et al.Women with adverse pregnancy outcomes have higher odds of midlife stroke: The population assessment of tobacco and health study. J Womens Health (Larchmt), 2021; 31(4):503–512; doi: 10.1089/jwh.2021.0184
57.
ParikhNI, CnattingiusS, DickmanPW, et al.Parity and risk of later-life maternal cardiovascular disease. Am Heart J, 2010; 159(2):215–221.e6; doi: 10.1016/j.ahj.2009.11.017
58.
ShiraziTN, HastingsWJ, RosingerAY, et al.Parity predicts biological age acceleration in post-menopausal, but not pre-menopausal, women. Sci Rep, 2020; 10(1):20522; doi: 10.1038/s41598-020-77082-2
59.
RoteSM, AngelJL. Gender-based pathways to cognitive aging in the Mexican-origin population in the United States: The significance of work and family. J Gerontol B Psychol Sci Soc Sci, 2021; 76(4):e165–e175; doi: 10.1093/geronb/gbaa189
60.
FujishiroK, MacDonaldLA, CroweM, et al.The role of occupation in explaining cognitive functioning in later life: Education and occupational complexity in a U.S. National Sample of Black and White Men and Women. J Gerontol B Psychol Sci Soc Sci, 2019; 74(7):1189–1199; doi: 10.1093/geronb/gbx112
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