HISTORY OF HYPERTENSIVE DISORDERS DURING PREGNANCY LINKED TO INCREASED RISK OF DEMENTIA
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 (
) in San Diego and virtually.
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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 (
). 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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