ApoE4 carriage is associated with 2.02 times higher prevalence of cognitive impairment in patients with intracranial atherosclerosis, especially in females.
Does ApoE4 carriage increase the prevalence of cognitive impairment in patients with intracranial atherosclerosis?
ApoE4 carriage is independently associated with a twofold increased odds of cognitive impairment in patients with intracranial atherosclerosis, with the effect partially mediated by worsening atherosclerosis severity.
Background: While the apolipoprotein E ε4 (ApoE4) allele is an established genetic risk factor for Alzheimer’s disease and links to cerebrovascular pathology, its specific impact on cognitive impairment in individuals with intracranial atherosclerosis remains undefined. We sought To investigate whether and how ApoE4 influences cognition in patients with intracranial atherosclerosis. Methods: This cross-sectional analysis utilized baseline data from a prospective multicenter cohort study at nine centers. Four hundred and nine patients with intracranial atherosclerosis (mean age 60 years; 55% male) were enrolled. Cognitive impairment, defined as mild cognitive impairment or dementia, was assessed using a comprehensive neuropsychological battery. ApoE4 carriage, intracranial atherosclerosis severity (via magnetic resonance angiography), plasma Alzheimer’s disease biomarkers (Aβ42/Aβ40, pTau217, GFAP, NfL), and neuroimaging markers (cerebral small vessel disease burden, brain atrophy) were evaluated. Multivariable logistic regression and mediation analyses were performed. Results: ApoE4 carriers had a higher prevalence of cognitive impairment compared to noncarriers (62% vs 48%). After full adjustment (age, sex, education, stroke or transient ischemic attack history, cerebral small vessel disease burden, Alzheimer’s disease biomarkers), ApoE4 carriage was associated with an increased prevalence of cognitive impairment (OR = 2.02; 95% CI, 1.10 to 3.76), This prevalence was stronger in females (OR = 4.90; 95% CI, 1.96 to 13.48). Mediation analysis revealed that the number of vessels with ≥50% stenosis possibly partially mediated the association between ApoE4 carriage and cognitive status (indirect effect: 10%), whereas Alzheimer’s disease biomarkers and cerebral small vessel disease burden did not. Conclusions: ApoE4 carriage is independently associated with increased prevalence of cognitive impairment in ICAS patients, particularly in females. The association was possibly partially mediated by worsening ICAS severity, but not by Alzheimer’s disease or cerebral small vessel disease. ApoE genotyping may help stratify patients with intracranial atherosclerosis for developing targeted interventions.
Cheng et al. (2026) studied this question. ApoE4 carriage is associated with 2.02 times higher prevalence of cognitive impairment in patients with intracranial atherosclerosis, especially in females.