Preeclampsia as a reversible risk factor for Alzheimer’s disease: A prospective MRI study on morphological changes of the cerebral cortex and impairment of cognitive functions - 10/01/26

Doi : 10.1016/j.tjpad.2025.100475

Yuanyuan Wang ^a,^b,^c,^{^{1
Yuanyuan Wang and Meng Li contributed equally and share the first authorship.}} , Meng Li ^d,^{^{1
Yuanyuan Wang and Meng Li contributed equally and share the first authorship.}} , Tao Chen ^e , Yanli Li ^e,^f , Qingqing Wang ^e , Xinyue Zhang ^b , Na Wang ^b , Linfeng Yang ^e,^{^{2
Wenying Nie, Lingfei Guo and Linfeng Yang contributed equally and share the corresponding author.},}^⁎ , Lingfei Guo ^b,^{^{2
Wenying Nie, Lingfei Guo and Linfeng Yang contributed equally and share the corresponding author.},}^⁎ , Wenying Nie ^e,^{^{2
Wenying Nie, Lingfei Guo and Linfeng Yang contributed equally and share the corresponding author.},}^⁎
^a Binzhou medical university, Guanhai Road No.346, Yantai, Shandong 264003, China
^b Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jing-wu Road No. 324, Jinan 250021, Shandong, China
^c Beijing Friendship Hospital, Affiliated to Capital Medical University, No. 95, Yong'an Road, Xicheng District, Beijing 100032, China
^d Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany
^e Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, 2 Jian-guo xiao jing-san Road, Jinan, Shandong Province, China
^f Heze Maternal and Child Health Hospital. No. 399, Guangzhou Road, Mudan District, Heze City 274000, Shandong Province, China

^⁎Corresponding author at: Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, 2 Jian-guo xiao jing-san Road, Jinan, Shandong Province 250001, China.Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University2 Jian-guo xiao jing-san RoadJinanShandong Province250001China^⁎⁎Corresponding author at: Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jing-wu Road No. 324, Jinan 250021, Shandong, China.Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of EducationDepartment of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJing-wu Road No. 324JinanShandong250021China^⁎⁎⁎Corresponding author at: Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China. 2 Jian-guo xiao jing-san Road, Jinan, Shandong 250001, China.Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China. 2 Jian-guo xiao jing-san Road, Jinan, Shandong 250001, China

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Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 10 January 2026

Highlights

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This study, for the first time, identified specific alterations in cortical thickness and cortical surface area in patients with preeclampsia. These changes closely resemble the early pathological features observed in Alzheimer's disease. The cortical thickness in brain regions, including the right posterior cingulate tail, anterior cingulate head, posterior cingulate, and superior frontal gyrus, was significantly lower in the preeclampsia group than in the PHC group. These structural changes were strongly associated with clinical factors such as elevated MAP, high prepregnancy BMI, and decreased scores on the MoCA and AVLT. These findings suggest that these cortical alterations may be involved in the pathophysiological mechanisms of cognitive impairment mediated by MAP and prepregnancy BMI. Furthermore, they may represent the structural basis underlying cognitive dysfunction in preeclampsia, providing insights into the microstructural evolution of the brain and its relationship with cognitive changes. It also may represent one of the key early alterations in brain microstructure associated with Alzheimer's disease, highlighting the importance of carefully evaluating a patient's history of preeclampsia in clinical assessment and risk stratification. Longitudinal analyses have confirmed that preeclampsia is associated with reversible changes in cortical thickness and recoverable memory decline. However, no significant recovery in overall cognitive function or associated serological markers has been reported to date.

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Abstract

Purpose

To investigate the cross-sectional and longitudinal alterations in cortical thickness and surface area and Cognitive Impairment among patients with preeclampsia.

Methods

The thickness and surface area of the cerebral cortex were systematically segmented from MRI using the automated cortical segmentation software FreeSurfer, and the corresponding values for each brain region were accurately quantified. Data collection includes the clinical characteristics, serological markers of proteins associated with cognitive function, and cognitive assessments.

Results

Compared with healthy pregnancies, the cortical thicknesses of the right caudal anterior cingulate (R-CACg), right posterior cingulate (R-PoCg), right rostral anterior cingulate (R-RoACg), and right superior frontal (R-SF) in the preeclampsia group exhibited significant alterations. Notably, the change in the R-SF was specific to preeclampsia and was not associated with normal physiological pregnancies. Mediation analysis further confirmed that elevated prepregnancy BMI was directly associated with reduced Symbol Digit Modalities Test scores and indirectly contributed to cognitive decline through an increase in MAP. The cortical thickness of left pars opercularis was identified as a key component in this underlying mechanism. No statistically significant changes in cortical surface area were observed in patients with preeclampsia. Follow-up studies have indicated that cortical thickness alterations in brain regions associated with preeclampsia demonstrate signs of recovery. Among cognitive-related test indicators, only the Auditory Word Learning Test exhibited a statistically significant improvement.

Conclusion

The cortical thickness alterations in the R-CACg, R-PoCg, R-RoACg, and R-SF of patients with preeclampsia may represent the structural basis for cognitive impairment. Longitudinal studies have confirmed the neuroplasticity of cortical thickness changes and the potential for recovery from preeclampsia-related memory deficits.

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Graphical abstract

Image, graphical abstract

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Keywords : Magnetic resonance imaging, Cerebral cortical thickness and surface area, Preeclampsia, Mediation analysis, Cognitive functions, Longitudinal study

Abbreviations : CNS, AD, Aβ1–42, P-tau181, T-tau, NPHCs, PHCs, MoCA, SDMT, AVLT, SCWT, ANOVA, TE, DE, IE, R, L, CACg, PoCg, RoACg, SF, Op, MAP, BMI, GMV, rs-FMRI