HISTORY OF HYPERTENSIVE DISORDERS DURING PREGNANCY LINKED TO INCREASED RISK OF DEMENTIA

Alzheimer's Association

2022/8/5 12:20

PR97325

 

SAN DIEGO, Aug. 3, 2022 /PRNewswire=KYODO JBN/ --

 

Experiences of high blood pressure disorders during pregnancy are associated

with an increased risk of vascular dementia and accelerated brain aging,

according to studies reported today at the Alzheimer's Association

International Conference(R)) (AAIC(R)) 2022 (

https://c212.net/c/link/?t=0&l=en&o=3611257-1&h=4085809890&u=https%3A%2F%2Fwww.alz.org%2Faaic&a=Alzheimer%27s+Association+International+Conference

) in San Diego and virtually.

 

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Logo - https://mma.prnewswire.com/media/1869584/AAIC22_purple_font_rgb_Logo.jpg

 

Hypertensive disorders of pregnancy (HDP) -- conditions of high blood pressure

including chronic/gestational hypertension and preeclampsia -- have been

strongly linked to heart disease in later life, but, before today, little

research has connected these disorders with cognition. The key findings

presented at AAIC 2022 include:

 

    -- Women with a history of HDP were more likely to develop vascular

       dementia -- a decline in thinking skills caused by conditions that

       block or reduce blood flow to the brain -- later in life, compared

       to women with non-hypertensive pregnancies.

    -- Experience of HDP, specifically high blood pressure during pregnancy,

       was associated with white matter pathology, a predictor of accelerated

       cognitive decline, 15 years after pregnancy.

    -- Women with a history of severe preeclampsia had significantly higher

       levels of beta amyloid, an Alzheimer's-related brain change, as

       measured in blood, compared to women with non-hypertensive pregnancies.

 

Affecting nearly 1 in 7 hospital deliveries, HDP is one of the leading causes

of morbidity and mortality in birthing persons and fetuses worldwide. These

conditions impact Black, Latino, Asian/Pacific Islander and Native American

populations at disproportionately high rates.

 

"This is among the first longitudinal data linking hypertensive disorders of

pregnancy with dementia in a large study cohort," said Claire Sexton, D.Phil.,

senior director of scientific programs and outreach at the Alzheimer's

Association. "Considering the serious short- and long-term implications of HDP,

early detection and treatment are vital to protect both the pregnant person and

baby."

 

"These data illuminate the importance of prenatal care and monitoring the

long-term health of pregnant people," said Sexton. "Those who experience any

changes with their memory and cognition should have a discussion with their

health care provider."

 

HDP associated with higher risk of vascular dementia

 

To explore the association between HDP and later-life dementia, Karen Schliep,

Ph.D., MSPH, assistant professor in family and preventive medicine at

University of Utah Health, and colleagues, performed a retrospective cohort

study among 59,668 women who had experienced a pregnancy.

 

Women with a history of HDP had a 1.37 times higher adjusted risk of all-cause

dementia after taking into account maternal age, year of childbirth and parity

than women with non-hypertensive pregnancies. HDP was associated with a 1.64

times higher risk of vascular dementia and 1.49 times higher risk of other

related dementia, but not Alzheimer's disease. Gestational hypertension and

preeclampsia/eclampsia showed similar magnitudes in risk for vascular dementia.

 

"Our results confirm previous findings that preeclampsia is most strongly

associated with vascular dementia compared to Alzheimer's or other types of

dementia," said Schliep. "They further suggest that vascular dementia risk may

be just as high for women with a history of gestational hypertension as for

preeclampsia."

 

HDP associated with white matter pathology 15 years post-pregnancy

 

Given the well-established association between HDP and long-term

cerebrovascular health, Rowina Hussainali, M.Sc., a doctoral student in

epidemiology and obstetrics and gynecology at the Erasmus MC Medical Center,

Netherlands, and colleagues, aimed to examine the associations between HDP and

markers of vascular brain pathology 15 years after pregnancy.

 

The researchers examined 538 women, 445 with a non-hypertensive pregnancy and

93 with HDP, from the Generation R study. Pregnant women with an expected

delivery date between April 2002 and January 2006 were included. Fifteen years

later, some of these women underwent magnetic resonance imaging to assess brain

tissue volumes as well as other markers that could indicate pathology.

 

Hussainali and team found women with prior HDP had 38% more white matter

pathology (indicative of the wearing away of brain tissue) compared to women

with previous non-hypertensive pregnancy. This association was driven by women

with gestational hypertension, who had 48% more white matter pathology compared

to women with previous normotensive pregnancy. No differences were found with

other markers of brain pathology, such as infarcts or cerebral microbleeds. The

development of chronic hypertension after pregnancy strengthened this result,

especially in women with previous gestational hypertension.

 

"These data clearly indicate that a history of HDP was associated with more

damage to the brain 15 years after pregnancy -- damage that could have lasting

impacts on cognition," said Hussainali. "Women with a history of HDP should be

evaluated and treated early for hypertension and other cardiovascular risk

factors."

 

Preeclampsia linked to increased markers of brain inflammation

 

Preeclampsia is a severe hypertensive disorder of pregnancy that affects up to

5-8% of pregnancies (

https://c212.net/c/link/?t=0&l=en&o=3611257-1&h=2033610123&u=https%3A%2F%2Fwww.preeclampsia.org%2Fwomen-and-families&a=5-8%25+of+pregnancies

). A large body of data indicates that women with a history of preeclampsia

have an accumulation of health risk factors later in life, including heart

disease. As severe preeclampsia has been associated with the highest risks for

cerebrovascular disease, Sonja Suvakov, M.D., Ph.D., postdoctoral research

fellow and assistant professor of medicine at Mayo Clinic, and team, explored

whether vesicles -- small fluid-filled pouches -- released from brain cells

would be detectable in women years after their affected pregnancies.

 

The researchers found that women with a history of severe preeclampsia had

significantly higher concentrations of extracellular vesicles positive for

amyloid beta, a protein that makes up one of the hallmark brain lesions of

Alzheimer's. They also found a significant increase of extracellular vesicles

positive for markers of brain endothelium damage and inflammation. Similarly,

circulating levels of beta amyloid were also increased.

 

"These findings indicate that women with a history of preeclampsia have

increased levels of markers of neurovascular damage which may negatively impact

their cognitive skills," said Suvakov. "Further research is required to fully

understand the neurodegenerative and cognitive risks that a history of

hypertensive disorders confers on women throughout life."

 

About the Alzheimer's Association International Conference(R) (AAIC(R))

The Alzheimer's Association International Conference (AAIC) is the world's

largest gathering of researchers from around the world focused on Alzheimer's

and other dementias. As a part of the Alzheimer's Association's research

program, AAIC serves as a catalyst for generating new knowledge about dementia

and fostering a vital, collegial research community.

 

AAIC 2022 home page: www.alz.org/aaic/

AAIC 2022 newsroom: www.alz.org/aaic/pressroom.asp

AAIC 2022 hashtag: #AAIC22

 

About the Alzheimer's Association(R)

The Alzheimer's Association is a worldwide voluntary health organization

dedicated to Alzheimer's care, support and research. Our mission is to lead the

way to end Alzheimer's and all other dementia -- by accelerating global

research, driving risk reduction and early detection, and maximizing quality

care and support. Our vision is a world without Alzheimer's and all other

dementia(R). Visit alz.org (

https://c212.net/c/link/?t=0&l=en&o=3611257-1&h=573595038&u=https%3A%2F%2Fwww.alz.org%2F&a=alz.org

) or call 800.272.3900.

 

    -- Karen Schliep, Ph.D., MSPH, et al. What subtypes are driving the

       association between hypertensive disorders of pregnancy and dementia?

       Findings from an 80-year retrospective cohort study (Funders: National

       Institute on Aging, National Center for Research Resources, National

       Cancer Institute)

    -- Rowina Hussainali, M.Sc., et al. Hypertensive disorders of pregnancy

       and markers of vascular brain pathology after 15 years: a prospective

       cohort study (Funders: Preeclampsia Foundation; Coolsingel Foundation;

       Erasmus MC, Erasmus University Rotterdam, Netherlands Organization for

       Health Research and Development, Netherlands Organization for

       Scientific Research, Ministry of Health, Welfare and Sport; Ministry

       of Youth and Families; European Research Council)

    -- Sonja Suvakov, M.D., Ph.D., et al. Circulating extracellular vesicles

       of neurovascular origin are elevated in women with severe preeclampsia

       years after their affected pregnancies

 

*** AAIC 2022 news releases may contain updated data that does not match what

is reported in the following abstracts.

 

Proposal ID: 62343

Title: What subtypes are driving the association between hypertensive disorders

of pregnancy and dementia? Findings from an 80-year retrospective cohort study

Background: We recently found that women with, versus without, a history of HDP

had a higher hazard of all-cause dementia, vascular dementia (VaD), and

other/unspecified dementia, but not Alzheimer's disease (AD). Here, we assess

associations of HDP subtypes with later life dementias.

Methods: We performed a retrospective cohort study among women with at least 1

singleton pregnancy (1939–2019) in Utah. Classification of HDP was done via

birth certificates (text string, 1939–1977; ICD9 codes, 1978–1988; and check

boxes with additional text, 1989–2013) with death certificates and inpatient

records used for validation. Classification of dementia was assessed using ICD

9/10 codes via death, inpatient, and Medicare records. HDP exposed women

(n=19,989) were one-to-two matched with unexposed women (n=39,679) by 5-year

age groups, year of childbirth, and parity at the time of pregnancy (Figure 1).

Cox regression models were used to estimate adjusted Hazard Ratios (aHR) and

95% CI for HDP subtypes with all-cause and specific dementias.

Results: HDP pregnancies were comprised of preeclampsia/eclampsia (65.9%) and

gestational hypertension (33.5%). The remaining HDP cases were due to HELLP

syndrome (0.6%), which we did not evaluate here due to small case count.

Incidence of dementia over follow-up (1979–2019) was 4.1%; of these, 70% were

other/unspecified, 24% were AD, and 6% were VaD. Women with a history of

preeclampsia/eclampsia, compared to unexposed, had a 1.38 higher hazard of

all-cause dementia, while women with gestational hypertension had a 1.36 higher

hazard (Table 1). Breaking down by dementia subtypes, women with a history of

preeclampsia/eclampsia had a 1.51 higher hazard of other/unspecified dementia,

while women with gestational hypertension had a 1.31 higher hazard. The

strength of association of gestational hypertension with VaD was 2.75, nearly

double that for preeclampsia/eclampsia, which was 1.58. HDP subtypes were not

associated with AD.

Conclusion: Our results are in line with the largest study to date conducted in

Denmark that found preeclampsia to be most strongly associated with VaD

compared to other dementia subtypes. Our results further suggest that risk of

VaD may be just as high for women with a history of gestational hypertension as

for preeclampsia.

 

Presenting Author

Karen Schliep, Ph.D., MSPH

University of Utah, United States

 

Proposal ID: 62354

Title: Hypertensive disorders of pregnancy and markers of vascular brain

pathology after 15 years: a prospective cohort study

Background: Substantial evidence suggests an association between hypertensive

disorders of pregnancy (HDP) and long term cerebrovascular health. We aimed to

determine the associations between HDP and markers of vascular brain pathology

fifteen years after pregnancy

Method: This was a nested cohort study embedded in a population-based

prospective cohort followed from early pregnancy. We included 538 women, 445

(82.7%) with normotensive index pregnancies and 93 (17.2%) with HDP in the

index pregnancy. Fifteen years after pregnancy (median of 14.6 years 90% range

14.0; 15.7), women had a mean age of 46.5 years (SD = 4.2). These women

underwent magnetic resonance imaging to assess brain tissue volumes as well as

white matter hyperintensities (WMH), lacunar infarcts, and cerebral microbleeds

as markers of vascular brain pathology.

Result: Women with prior HDP had 38% (95% CI: [8% ; 75%]) higher WMH volume

compared to women with previous normotensive pregnancy. This association was

driven by women with gestational hypertension, who had 48% (95% CI: [11% ;

95%]) higher WMH volume compared to women with previous normotensive pregnancy.

No differences were found with infarcts or cerebral microbleeds. The

development of chronic hypertension after pregnancy strengthened this result,

especially in women with previous gestational hypertension.

Conclusion: A history of HDP was associated with more WMH burden fifteen years

after pregnancy. This effect was driven by women with previous gestational

hypertension. The development of chronic hypertension after pregnancy

contributed to this effect. Women with a history of HDP should be evaluated and

treated early for hypertension and other cardiovascular risk factors.

 

Presenting author:

Rowina Hussainali, M.Sc.

Erasmus MC University Medical Center, Netherlands

 

Proposal ID: 62360

Title: Circulating extracellular vesicles of neurovascular origin are elevated

in women with severe preeclampsia years after their affected pregnancies

Background: Preeclampsia (PE), a pregnancy specific hypertensive disorder, has

been associated with elevated risk for strokes, cognitive decline, and smaller

brain volumes later in life. As severe PE has been associated with the highest

risks for cerebrovascular disease, we hypothesized that circulating

extracellular vesicles (EVs) of neurovascular origin will be detectable in

women years after severe PE as a marker of persistent neurovascular damage and

amyloid-Beta.

Method: A cohort of 40 women with histories of normotensive pregnancies

(control group) and age- and parity-matched to 40 women with history of mild

(n=33) and severe (n=7) PE were identified using the Rochester Epidemiology

Project. Diagnosis of severe PE was ascertained based on clinical criteria

(Table). While none of the women had any major cardiovascular events, our

previous study of this cohort has demonstrated that total gray matter volumes

were smaller in women with a history of preeclampsia and late-life hypertension

compared with the other groups. Blood-borne EVs derived from neurovascular

cellular activation were determined by standardized digital flow cytometry.

Plasma concentration of amyloid-Beta was measured by ELISA. Differences among

the groups were tested by ANOVA, with the least difference test for post hoc

analysis. The association between EVs and MRI brain imaging was assessed by

Pearson correlation coefficient.

Result: Women with history of severe PE had a significantly higher

concentration of amyloid-Beta carrying EVs compared to controls (p=0.003). EVs

positive for the markers of blood-brain barrier- endothelial damage (LDL-R) and

inflammatory coagulation pathway activator (tissue factor), were significantly

higher in women with history of severe PE compared to controls (p=0.008 and

p=0.002, respectively), as well as to the women with history of mild PE. Plasma

concentration of total amyloid-Beta was also significantly greater in women

with history of severe vs. mild PE (p=0.037) (Table). The number of tissue

factor positive EVs was negatively correlated with total gray matter volume

(cm3) (p<0.05).

Conclusion: Women with a history of severe PE demonstrate elevated levels of

markers of neuroinflammation and neurovascular damage, as well as greater

amyloid-Beta secretion. Excessive inflammation may contribute to previously

described brain atrophy in these women.

 

Presenting Author:

Sonja Suvakov, M.D., Ph.D.

Mayo Clinic, Minnesota, United States

 

SOURCE  Alzheimer's Association

 

CONTACT:  Alzheimer's Association Media Line, +1 312.335.4078, media@alz.org,

OR AAIC 2022 Press Office, aaicmedia@alz.org; OR Karen Schliep, Ph.D., MSPH,

Karen.Schliep@utah.edu; OR Rowina Hussainali, M.Sc., r.hussainali@erasmusmc.nl;

OR Sonja Suvakov, M.D., Ph.D., suvakov.sonja@mayo.edu

 

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