Abstract
This study aimed to investigate the association between hypertensive disorders of pregnancy (HDP) and subsequent risk of dementia using a systematic review and meta-analysis of cohort studies. We searched PubMed and Scopus for eligible studies that investigated the association between HDP and dementia risk. Using the random-effects model, pooled hazard ratio (HR) and 95% confidence interval (CI) of dementia risk in women with HDP were calculated. We applied the I2 statistic to measure heterogeneity across studies and the test for funnel plot asymmetry to evaluate publication bias. Six cohort studies were eligible: three from the United States, two from Sweden, and one from Denmark. When combined, HDP was associated with the risk of dementia: pooled HR (95% CI) = 1.31 (1.12, 1.53). The heterogeneity across studies was moderate (I2 = 47.3%, p-heterogeneity = 0.091), but no signs of publication bias were detected. The association of HDP with vascular dementia was stronger than that with Alzheimer’s disease: pooled HRs (95% CIs) = 1.66 (1.13, 2.43) and 1.29 (0.97, 1.72), respectively. In conclusion, HDP was associated with a higher risk of dementia and this association was more prominent with vascular dementia.
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References
GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022;7:e105–e25.
Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and management of dementia: review. JAMA. 2019;322:1589–99.
Seidel D, Thyrian JR. Burden of caring for people with dementia - comparing family caregivers and professional caregivers. A descriptive study. J Multidiscip Health. 2019;12:655–63.
Durgante H, Contreras ML, Backhouse T, Mavrodaris A, Ferreira MG, Paulo DLV, et al. Challenges in dementia care: comparing key issues from Brazil and the United Kingdom. Dement Neuropsychol. 2020;14:216–22.
Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396:413–46.
Sierra C. Hypertension and the risk of dementia. Front Cardiovasc Med. 2020;7:5.
Metoki H, Iwama N, Hamada H, Satoh M, Murakami T, Ishikuro M, et al. Hypertensive disorders of pregnancy: definition, management, and out-of-office blood pressure measurement. Hypertens Res. 2022;45:1298–309.
Postma IR, Bouma A, Ankersmit IF, Zeeman GG. Neurocognitive functioning following preeclampsia and eclampsia: a long-term follow-up study. Am J Obstet Gynecol. 2014;211:37.e1–9.
Fields JA, Garovic VD, Mielke MM, Kantarci K, Jayachandran M, White WM, et al. Preeclampsia and cognitive impairment later in life. Am J Obstet Gynecol. 2017;217:74.e1–74.e11.
Miller KB, Miller VM, Barnes JN. Pregnancy history, hypertension, and cognitive impairment in postmenopausal women. Curr Hypertens Rep. 2019;21:93.
Soma-Pillay P, Suleman FE, Makin JD, Pattinson RC. Cerebral white matter lesions after pre-eclampsia. Pregnancy Hypertens. 2017;8:15–20.
Targosz-Gajniak M, Siuda J, Ochudło S, Opala G. Cerebral white matter lesions in patients with dementia - from MCI to severe Alzheimer’s disease. J Neurol Sci. 2009;283:79–82.
van Dijk M, van Bezu J, Poutsma A, Veerhuis R, Rozemuller AJ, Scheper W, et al. The pre-eclampsia gene STOX1 controls a conserved pathway in placenta and brain upregulated in late-onset Alzheimer’s disease. J Alzheimers Dis. 2010;19:673–9.
Kalkunte SS, Neubeck S, Norris WE, Cheng SB, Kostadinov S, Vu Hoang D, et al. Transthyretin is dysregulated in preeclampsia, and its native form prevents the onset of disease in a preclinical mouse model. Am J Pathol. 2013;183:1425–36.
Basit S, Wohlfahrt J, Boyd HA. Pre-eclampsia and risk of dementia later in life: nationwide cohort study. BMJ. 2018;363:k4109.
Garovic VD, White WM, Vaughan L, Saiki M, Parashuram S, Garcia-Valencia O, et al. Incidence and long-term outcomes of hypertensive disorders of pregnancy. J Am Coll Cardiol. 2020;75:2323–34.
Schliep KC, Shaaban CE, Meeks H, Fraser A, Smith KR, Majersik JJ, et al. Hypertensive disorders of pregnancy and subsequent risk of Alzheimer’s disease and other dementias. Alzheimers Dement. 2023;15:e12443.
Wang K, Guo K, Ji Z, Liu Y, Chen F, Wu S, et al. Association of preeclampsia with incident dementia and Alzheimer’s disease among women in the Framingham Offspring Study. J Prev Alzheimers Dis. 2022;9:725–30.
Andolf EG, Sydsjö GC, Bladh MK, Berg G, Sharma S. Hypertensive disorders in pregnancy and later dementia: a Swedish National Register Study. Acta Obstet Gynecol Scand. 2017;96:464–71.
Nelander M, Cnattingius S, Åkerud H, Wikström J, Pedersen NL, Wikström AK. Pregnancy hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older: a cohort study. BMJ Open. 2016;6:e009880.
Andolf E, Bladh M, Möller L, Sydsjö G. Prior placental bed disorders and later dementia: a retrospective Swedish register-based cohort study. BJOG. 2020;127:1090–9.
Abheiden CN, van Doornik R, Aukes AM, van der Flier WM, Scheltens P, de Groot CJ. Hypertensive disorders of pregnancy appear not to be associated with Alzheimer’s disease later in life. Dement Geriatr Cogn Dis Extra. 2015;5:375–85.
Sukmanee J, Liabsuetrakul T. Risk of future cardiovascular diseases in different years postpartum after hypertensive disorders of pregnancy: a systematic review and meta-analysis. Medicine. 2022;101:e29646.
Samara AA, Liampas I, Dadouli K, Siokas V, Zintzaras E, Stefanidis I, et al. Preeclampsia, gestational hypertension and incident dementia: a systematic review and meta-analysis of published evidence. Pregnancy Hypertens. 2022;30:192–7.
Schliep KC, Mclean H, Yan B, Qeadan F, Theilen LH, de Havenon A, et al. Association between hypertensive disorders of pregnancy and dementia: a systematic review and meta-analysis. Hypertension. 2023;80:257–67.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.
Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed on 6 July 2022.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
Higgins J, Thompson S, Deeks J, Altman D. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.
Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.
Theilen LH, Fraser A, Hollingshaus MS, Schliep KC, Varner MW, Smith KR, et al. All-cause and cause-specific mortality after hypertensive disease of pregnancy. Obstet Gynecol. 2016;128:238–44.
Pankiewicz K, Szczerba E, Maciejewski T, Fijałkowska A. Non-obstetric complications in preeclampsia. Prz Menopauzalny. 2019;18:99–109.
Rayes B, Ardissino M, Slob EAW, Patel KHK, Girling J, Ng FS. Association of hypertensive disorders of pregnancy with future cardiovascular disease. JAMA Netw Open. 2023;6:e230034.
Melchiorre K, Thilaganathan B, Giorgione V, Ridder A, Memmo A, Khalil A. Hypertensive disorders of pregnancy and future cardiovascular health. Front Cardiovasc Med. 2020;7:59.
Strandhagen E, Berg C, Lissner L, Nunez L, Rosengren A, Torén K, et al. Selection bias in a population survey with registry linkage: potential effect on socioeconomic gradient in cardiovascular risk. Eur J Epidemiol. 2010;25:163–72.
Lewandowska M, Więckowska B. The influence of various smoking categories on the risk of gestational hypertension and pre-eclampsia. J Clin Med. 2020;9:1743.
Zhong G, Wang Y, Zhang Y, Guo JJ, Zhao Y. Smoking is associated with an increased risk of dementia: a meta-analysis of prospective cohort studies with investigation of potential effect modifiers. PLoS One. 2015;10:e0118333.
Braunthal S, Brateanu A. Hypertension in pregnancy: pathophysiology and treatment. SAGE Open Med. 2019;7:2050312119843700.
Funding
This study was supported by the Intramural Research Fund (20-4-9) for the cardiovascular diseases of the National Cerebral and Cardiovascular Center, the JST Grant Number JPMJPF2018, and the Japan Agency for Medical Research and Development (dk0207025).
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All authors made a substantial contribution to this work. Conceptualization (AA and YK), data collection (AA and MT), analysis and manuscript writing (AA), resources (YK), and revision and editing (AA, RK, MT, YS, SN, KS, HK, QG, CM, and YK).
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Arafa, A., Kashima, R., Shimamoto, K. et al. Hypertensive disorders of pregnancy and the risk of dementia: a systematic review and meta-analysis of cohort studies. Hypertens Res 47, 859–866 (2024). https://doi.org/10.1038/s41440-023-01520-7
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DOI: https://doi.org/10.1038/s41440-023-01520-7
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