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. 2025 Aug 29;25(1):363.
doi: 10.1186/s12883-025-04371-6.

APOE ε2 is associated with reduced risk of early post-stroke cognitive impairment but not with long-term functional outcome

Yangbo Hou #  1 , Shuyun Hua #  2 , Zhi Guo  2 , Jiwei Cheng  1 , Guoyi Li  3 , Liangqi Wang  4   5 , Qian Xiao  6
Affiliations

APOE ε2 is associated with reduced risk of early post-stroke cognitive impairment but not with long-term functional outcome

Yangbo Hou et al. BMC Neurol. .

Abstract

Background: The associations between APOE genotype and early cognitive impairment and long-term functional prognosis after acute ischemic stroke (AIS) are uncertain.

Objective: To investigate the associations between APOE genotype and early cognitive impairment and long-term functional prognosis after AIS.

Methods: Our study was a single-center, prospective cohort study, that included 109 patients with AIS. At baseline, APOE genotype, cognition and white matter hyperintensities (WMH) were assessed within 2 weeks of stroke onset. At 3 months and 18 months, the modified Rankin scale (mRS) was used to assess the functional outcome after stroke.

Results: ε2 carriers had better cognitive performance than ε2 noncarriers did in the Montreal Cognitive Assessment (MoCA, p = 0.003) and the Trail Making Test (TMT, p = 0.038). Multivariate logistic regression analysis revealed that ε2 was an independent protective factor for early post-stroke cognitive impairment (OR 0.213, 95% CI 0.055–0.820), whereas ε4 was not associated with early post-stroke cognitive impairment (OR 2.582, 95% CI 0.314–21.219). ε2 had no significant effect on WMH, whereas ε4 aggravated WMH, especially in the deep white matter (DWM). No significant interaction effect between the Fazekas score and ε2 on early post-stroke cognitive impairment was found. Female sex (OR 7.081, 95% CI 2.531–19.813), admission NIHSS score (OR 1.265, 95% CI 1.062–1.507), and DWM Fazekas score (OR 2.224, 95% CI 1.106–4.469) were independent risk factors for long-term unfavorable prognosis after ischemic stroke.

Conclusion: ε2 was associated with reduced risk of early post-stroke cognitive impairment, but not with the favorable long-term functional prognosis after stroke.

Keywords: Apolipoproteins e; Cognitive dysfunction; Genotype; Ischemic stroke; Leukoaraiosis; Prognosis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of Putuo Hospital, Shanghai University of Traditional medicine (PTEC-A-2020-66-1). All written informed consent was obtained from the participants or their legal representatives. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Receive operating characteristic curves for the prediction of 18-month stroke outcome in AIS patients. Abbreviations: PRE_1: the predicted probability based on the logistic regression model; DWM: deep white matter; NIHSS: National Institute of Health Stroke Scale
See this image and copyright information in PMC

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