Hypertension in pregnancy may be a risk factor for Alzheimer’s disease in Asians

Women with a history of hypertensive disorders in pregnancy are at increased risk of developing brain changes that lead to Alzheimer’s disease (AD), according to a study from Singapore.

In a local cohort of community-dwelling midlife women without dementia, serum p-tau217 levels were slightly higher among those with vs without a history of hypertension in pregnancy (mean, 0.30 vs 0.26 pg/ml; p=0.085). [J Prev Alzheimers Dis 2025;doi:10.1016/j.tjpad.2025.100316]

Serum p-tau217 levels were significantly associated with older age (mean difference [MD], 0.002, 95 percent confidence intervals [CI], 0.001–0.003), mild cognitive impairment (MD, 0.016, 95 percent CI, 0.001–0.032), lower BMI (<18.5 kg/m²) (MD, 0.068, 95 percent CI, 0.027–0.109), eGFR <60 mL/min/1.73 m² (MD, 0.132, 95 percent CI, 0.072–0.193), and the APOE4 carrier genotype (MD, 0.038, 95 percent CI, 0.018–0.058).

In an analysis that accounted for the above-mentioned factors, hypertension in pregnancy emerged as an independent risk factor for increased serum p-tau217 levels (MD, 0.040, 95 percent CI, 0.013–0.067).

“To our knowledge, this is the first investigation into the relationship between the history of pregnancy hypertension and AD pathology many decades later,” according to the investigators.

Hypertension in pregnancy can progress into more severe conditions such as pre-eclampsia and eclampsia. The investigators pointed out that in women with pre-eclampsia, cerebral blood velocity responses can be altered, which is linked to changes in brain function and structure. [Am J Obstet Gynecol 2022;226:S786-S803; Curr Hypertens Rep 2019;21:1-8]

“Our findings merit consideration of a history of hypertensive disorders in pregnancy as a potential risk factor for AD,” they said.

The analysis included 743 women (mean age 62.9 years, 82.3 percent Chinese) recruited from four well-women clinics at the National University Hospital, Singapore. More than half of them (58.5 percent) were overweight or obese, 48.0 percent had hypertensive disease at midlife, 42.3 percent had mild cognitive impairment (Montreal Cognitive Assessment scores ≤25), 22.0 percent had reduced renal function (eGFR <90 mL/min/1.73 m²), and 16.7 percent were carriers of the high risk APOE4 genotype.

Of the women, 68 (9.2 percent) reported a history of hypertension in pregnancy. The mean age at onset was 29.3 years, and the mean latency period between pregnancy and p-tau analysis was 32.1 years. Roughly three quarters (74.4 percent) of the cases of hypertension in pregnancy occurred during the first pregnancy, 28.2 percent occurred more than once, and 27.3 percent required hospital admission.

Despite the study’s reliance on self-reported pregnancy hypertension history, the investigators emphasized that they used a serum p-tau217 immunoassay that has been validated to accurately identify AD, comparable with results using cerebral spinal fluid biomarkers and superior to brain atrophy assessments, with reproducible cut-offs across cohorts that can detect longitudinal changes at the preclinical disease stage. Additionally, key confounders such as age, mild cognitive impairment, hypertension, BMI, renal function, and APOE4 genotype were accurately and rigorously quantified. [JAMA Neurol 2024;81:255-263; Alzheimers Dement 2025;21:e70319; Neurology 2025;105:e213769]

In closing, the investigators stressed the need for obstetricians and primary care physicians to take a proactive approach to monitor women with a history of hypertension in pregnancy as a risk factor for AD signs of cognitive decline as they age, which can facilitate early clinical intervention.