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      Pre-eclampsia and risk of dementia later in life: nationwide cohort study

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      The BMJ
      BMJ Publishing Group Ltd.

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          Abstract

          Objective

          To explore associations between pre-eclampsia and later dementia, overall and by dementia subtype and timing of onset.

          Design

          Nationwide register based cohort study.

          Setting

          Denmark.

          Population

          All women with at least one live birth or stillbirth between 1978 and 2015.

          Main outcome measure

          Hazard ratios comparing dementia rates among women with and without a history of pre-eclampsia, estimated using Cox regression.

          Results

          The cohort consisted of 1 178 005 women with 20 352 695 person years of follow-up. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia (hazard ratio 3.46, 95% confidence interval 1.97 to 6.10) later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late onset disease (hazard ratio 6.53, 2.82 to 15.1) than for early onset disease (2.32, 1.06 to 5.06) (P=0.08). Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios only moderately; sensitivity analyses suggested that body mass index was unlikely to explain the association with vascular dementia. In contrast, only modest associations were observed for Alzheimer’s disease (hazard ratio 1.45, 1.05 to 1.99) and other/unspecified dementia (1.40, 1.08 to 1.83).

          Conclusions

          Pre-eclampsia was associated with an increased risk of dementia, particularly vascular dementia. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that pre-eclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways. Asking about a history of pre-eclampsia could help physicians to identify women who might benefit from screening for early signs of disease, allowing for early clinical intervention.

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          Most cited references20

          • Record: found
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          • Article: not found

          Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease.

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            Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis.

            There is increasing evidence that pre-eclampsia, a principal cause of maternal morbidity, may also be a risk factor for future cardiovascular and cerebrovascular events. This review aimed to assess the current evidence and quantify the risks of cardiovascular disease (CVD), cerebrovascular events and hypertension associated with prior diagnosis of pre-eclampsia. Medline and Embase were searched with no language restrictions, as were core journals and reference lists from reviews up until January 2012. Case-control and cohort studies which reported cardiovascular and cerebrovascular diseases or hypertension diagnosed more than 6 weeks postpartum, in women who had a history of pre-eclampsia relative to women who had unaffected pregnancies, were included. Fifty articles were included in the systematic review and 43 in the meta-analysis. Women with a history of pre-eclampsia or eclampsia were at significantly increased odds of fatal or diagnosed CVD [odds ratio (OR) = 2.28, 95% confidence interval (CI): 1.87, 2.78], cerebrovascular disease (OR = 1.76, 95% CI 1.43, 2.21) and hypertension [relative risk (RR) = 3.13, 95% CI 2.51, 3.89]. Among pre-eclamptic women, pre-term delivery was not associated with an increased risk of a future cardiovascular event (RR = 1.32, 95% CI 0.79, 2.22). Women diagnosed with pre-eclampsia are at increased risk of future cardiovascular or cerebrovascular events, with an estimated doubling of odds compared to unaffected women. This has implications for the follow-up of all women who experience pre-eclampsia, not just those who deliver pre-term. This association may reflect shared common risk factors for both pre-eclampsia and cardiovascular and cerebrovascular disease.
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              • Article: not found

              Cerebral white matter lesions and the risk of dementia.

              To study the association between white matter lesions (WML) in specific locations and the risk of dementia. The Rotterdam Scan Study, a prospective population-based cohort study. We scored periventricular and subcortical WML on magnetic resonance imaging and observed participants until January 2002 for incident dementia. General population. We included 1077 people aged 60 to 90 years who did not have dementia at baseline. Incident dementia by Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM III-R) criteria. During a mean follow-up of 5.2 years, 45 participants developed dementia. Higher severity of periventricular WML increased the risk of dementia, whereas the association between subcortical WML and dementia was less prominent. The adjusted hazard ratio of dementia for each standard deviation increase in periventricular WML severity was 1.67 (95% confidence interval, 1.25-2.24). This increased risk was independent of other risk factors for dementia and partly independent of other structural brain changes on magnetic resonance imaging. White matter lesions, especially in the periventricular region, increase the risk of dementia in elderly people.
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                Author and article information

                Contributors
                Role: statistician
                Role: chief statistician
                Role: senior researcher
                Journal
                BMJ
                BMJ
                BMJ-UK
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2018
                17 October 2018
                : 363
                : k4109
                Affiliations
                [1]Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
                Author notes
                Correspondence to: H Boyd hoy@ 123456ssi.dk
                Author information
                http://orcid.org/0000-0001-6849-9985
                Article
                bass045624
                10.1136/bmj.k4109
                6191824
                30333106
                55d9c6ae-bb1f-48eb-b656-2eae63100ff2
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 15 September 2018
                Categories
                Research
                1332

                Medicine
                Medicine

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