Long-term neurological consequences of hypertensive disorders of pregnancy: Implications for postpartum monitoring and intervention

Table 4 Cognitive outcomes following hypertensive disorders of pregnancy per PubMed analysis, including objective neuropsychological testing and subjective patient-reported measures

Ref.	Country/design	Exposure (HDP subtype)	Sample (exposed/ref)	Time since index pregnancy	Cognitive measure(s)	Main finding(s)	Notes/adjustments
Alers et al[42], 2023	Netherlands; population cohort	Prior PE	1036/527 ref	≤ 19 years	BRIEF-A executive and working memory composite	Executive function and working memory decrease (aRR: 9.20 and 7.94 at one year; sustained significance at up to 19 years postpartum)	Adjusted for age, BMI, and education
Wang et al[49], 2022	United States; Framingham Offspring study (longitudinal)	Prior PE	142/1107 ref (n = 1249)	Median 12 years	Dementia diagnosis (all-cause, Alzheimer’s, vascular)	PE → increase risk of all-cause dementia (HR: 1.56) and Alzheimer’s dementia (HR: 1.65)	Longitudinal adjudicated outcomes; adjusted for cardiovascular risk
Garovic et al[23], 2020	United States; retrospective cohort (Olmsted County)	GH, PE, superimposed HDP	571 HDP/1142 ref (mothers total number = 7544)	Median approximately 36 years	Dementia diagnosis	Dementia signal present but ns after multiple testing	Adjusted for education, smoking, obesity; CVD endpoints significant
Dayan et al[50], 2018	United States; retrospective cohort (CARDIA)	Prior HDP	193/375 ref (n = 568 total)	25 years at testing	Neuropsychological testing (digit symbol substitution test, Stroop Test Trial 3, Rey Auditory Verbal Learning Test)	Processing speed and executive function decrease (unadjusted P = 0.01-0.05; differences attenuated and ns after adjustment)	Adjusted for age, BMI, hypertension, education, and depression at approximately 18 years postpartum
Fields et al[51], 2017	United States; case-control (Mayo Clinic)	Prior eclampsia	40/40 ref	Approximately 35 years	Neuropsych battery (executive function, memory, attention; trail making B, logical memory I/II, verbal learning, auditory attention)	Executive and memory decrease (d = 0.5-2.0); cognitive impairment 20% vs 8%; CAC increase in impaired hPE group (P = 0.043)	Adjusted for age, education, hypertension, BMI, and medication use; ApoE-4 and mood symptoms were not explanatory
Mielke et al[46], 2016	United States; community cohort + MRI	History of HDP	208/1071 ref	Mid-late life	Processing speed (digit symbol, TMT-A, Stroop) decrease in HDP (all P ≤ 0.035); memory, language, executive ns	Processing speed decrease on digit symbol (P = 0.005), TMT-A (P = 0.035), and Stroop (P = 0.002); memory/Language/executive ns. Processing speed correlated with lower brain injury volume (b = -0.36, P = 0.004)	Adjusted for hypertension duration, nulliparity, and eGFR; results robust in sensitivity models
Postma et al[52], 2016	Netherlands; case-control MRI + neuropsych battery	Prior PE	46 eclamptic + 51 PE/47 ref	Approximately 6 years	Motor speed (TMT-5, P < 0.01); other domains ns	CFQ increase (44 ± 16 vs 36 ± 11, P < 0.001) and HADS increase (11 ± 6 vs 8 ± 5, P < 0.001) in HDP vs controls; no objective cognitive impairment on neuropsych testing	Subjective dysfunction persisted despite normal objective scores; WML not predictive of cognition
Nelander et al[30], 2016	Sweden; population cohort (≥ 65 years)	HDP ± proteinuria	419 HDP/2646 ref	Decades later	Registry diagnosis of dementia	Dementia: 7.6% vs 7.4% (HR: 1.19, 95%CI: 0.79-1.73); CVD: 22.9% vs 19.0% (HR: 1.29, 95%CI: 1.02-1.61); stroke: 13.4% vs 10.7% (HR: 1.36, 95%CI: 1.00-1.81)	Subgroup analysis by proteinuria; registry follow-up
Postma et al[45], 2014	Netherlands; cross-sectional questionnaires ± MRI subset	Eclampsia and PE	46 eclamptic + 51 PE/48 ref	Approximately 6-7 years	CFQ, HADS, neuropsych battery	CFQ and HADS increase in PE/eclampsia vs controls (P < 0.01); visuomotor speed slower (Trail Making B P < 0.001); other domains ns	Persistent subjective cognitive and mood symptoms post-HDP; not time-dependent

HDP: Hypertensive disorders of pregnancy; PE: Preeclampsia; Ref: Reference/control group; BRIEF-A: Behavior Rating Inventory of Executive Function - Adult Version; aRR: Adjusted risk ratio; BMI: Body mass index; HR: Hazard ratio; GH: Gestational hypertension; CVD: Cardiovascular disease; CAC: Coronary artery calcification; hPE: Hypertensive preeclampsia; TMT: Trail Making Test; eGFR: Estimated glomerular filtration rate; CFQ: Cognitive Failures Questionnaire; HADS: Hospital Anxiety and Depression Scale; ApoE-4: Apolipoprotein E ε4 allele; WML: White matter lesion; CI: Confidence interval.