Discussion

In this cross-sectional study of community-dwelling older adults aged ≥ 60 years, we found that carotid atherosclerotic plaque burden, quantified by carotid plaque score, was independently associated with possible MCI. Even after adjusting for age, sex and education, higher plaque scores were associated with significantly greater odds of cognitive impairment. Additionally, increased ICA RI was associated with possible MCI, suggesting that both structural and hemodynamic markers of carotid disease are linked to cognitive performance. Domain-specific analyses further revealed that plaque burden was most strongly associated with impairments in visuospatial abilities and language performance. Together, these findings highlight a potential role for subclinical extracranial vascular pathology in domain-specific cognitive performance in aging populations.

Our findings are broadly consistent with a large body of evidence linking carotid atherosclerosis with cognitive dysfunction across diverse populations. Liang et al. reported in a cohort of 932 adults that the presence of ≥ 3 carotid plaques was significantly associated with poorer semantic fluency, and that greater intima–media thickness (IMT) was associated with reductions in global cognition and semantic fluency12. Although they did not observe a statistically significant association between plaque count and global cognition, their results reinforce the relevance of structural atherosclerosis to cognitive health in midlife and older age. Several population-based studies have reported similar results. In Ugandan older adults, plaque presence was strongly associated with cognitive impairment, while the Beaver Dam Offspring Study also showed associations between plaque scores and multiple cognitive domains dysfunction in middle-aged participants13,14. Our findings extend this evidence by demonstrating that plaque burden remains cognitively associated even in a narrower, older age group (≥ 60 years) using MoCA, a tool more sensitive to mild deficits than the MMSE used in several prior studies. The Tokyo Oldest Old Survey similarly identified lower MMSE performance among participants aged ≥ 85 years with high plaque scores, underscoring the predictive value of plaque burden in the oldest populations15. Our sample differed by including younger elderly adults, yet findings were directionally aligned. Longitudinal data from the Three-City Study and the BRAVE study also support these findings, showing that carotid plaque—but not IMT—predicts either dementia incidence or poorer cognitive performance16,17. Mechanistic insight is suggested by studies such as CABLE, where plaque presence correlated with amyloid and tau pathology, indicating a potential link between extracranial vascular disease and Alzheimer-related processes18. Similarly, Lin et al. demonstrated that advanced carotid atherosclerosis predicted poorer executive, visuospatial, and orientation performance over 10 years, mirroring the domain-specific associations we observed in visuospatial and language function19. Evidence from cardiovascular cohorts further supports the cognitive relevance of carotid pathology. Among patients with coronary heart disease, Molshatzki et al. found that high IMT and bilateral plaques were associated with lower cognitive performance even after excluding individuals with prior stroke20. A large Spanish cohort also demonstrated poorer cognitive performance across multiple domains in adults with carotid plaque, independent of stenosis severity21. Studies involving imaging modalities also confirm these observations. In the Framingham Offspring Study, even moderate internal carotid stenosis (≥ 25%) was associated with deficits in executive and nonverbal memory22. The ACE 1950 Study found a weak but significant association between plaque score and MoCA scores, similar to our findings, though multivariable adjustments weakened the association—possibly due to the younger study population23. Interestingly, the Northern Manhattan Study did not find significant associations between plaque presence or area and cognitive outcomes, although IMT was linked to episodic memory and plaques were associated with greater white-matter hyperintensity burden24. The authors noted important racial and ethnic heterogeneity that may influence vascular–cognition relationships. Overall, the consistency of evidence across continents, ethnicities, and study designs reinforces the biological plausibility of our findings.

We found that ICA RI was significantly higher in participants with possible MCI and remained independently associated with cognitive impairment in multivariate analyses. Higher RI reflects increased distal vascular resistance, suggesting impaired microvascular perfusion or reduced arterial compliance. This aligns with several previous studies. Rinjani et al. reported higher RI values among individuals with cerebral small vessel disease (CSVD) markers, and Wardlaw et al. demonstrated consistent associations between increased carotid pulsatility indices and poorer processing speed and visuospatial function—even when degree of stenosis was not predictive25,26. The ANTIQUE substudy corroborated these observations, showing that carotid plaque width, age, diabetes, and hypertension were key determinants of elevated RI27. Importantly, the threshold for abnormal RI (> 0.63) aligns closely with our findings, where our participants with possible MCI had a median RI of 0.63. Together, these findings suggest that hemodynamic compromise—independent of the degree of stenosis—may be linked to cognitive performance.

Several mechanisms plausibly explain the link between carotid atherosclerosis and cognitive dysfunction. Chronic cerebral hypoperfusion: Plaque-related arterial stiffening and reduced cerebrovascular reserve may lead to sustained reductions in cerebral blood flow, preferentially affecting watershed regions and fronto-subcortical networks that support executive and processing speed functions28. Microembolization and silent infarcts: Atheromatous plaques, particularly those with complex morphology, may shed microemboli causing subclinical infarcts that accumulate to impair cognition, especially in domains sensitive to distributed white matter integrity29,30. Impaired cerebrovascular reactivity: Elevated ICA RI and related indices indicate reduced autoregulatory capacity; impaired reactivity has been associated with domain-specific cognitive deficits and may potentiate vulnerability to additional vascular or neurodegenerative insults31. Systemic endothelial dysfunction and inflammation: Shared risk factors (hypertension, diabetes, dyslipidemia) promote both carotid atherogenesis and cerebral microvascular injury through endothelial dysfunction, oxidative stress and inflammatory pathways32. These pathways likely interact and vary in relative importance among individuals; hemodynamic compromise may dominate in some, whereas embolic or inflammatory mechanisms may be more relevant in others.

Educational attainment demonstrated the strongest independent association with possible MCI in both multivariable models. This finding is consistent with the well-recognized influence of education on cognitive reserve and performance on cognitive screening instruments such as the MoCA33. Evidence from Egyptian and international cohorts consistently demonstrates that educational attainment modifies cognitive trajectories across aging34,35. Interestingly, while education predicts baseline cognitive performance, its influence on rate of decline is less clear36; however, our findings support its robust protective effect on cognitive status in late life. Although educational level was adjusted for in the multivariable analyses and MoCA-Basic was used for participants with limited educational attainment according to the study protocol, residual confounding or some degree of misclassification cannot be excluded because cognitive impairment was defined using screening instruments rather than comprehensive clinical and neuropsychological assessment.

Key strengths of this study include: (1) the use of the Montreal Cognitive Assessment (MoCA), which is more sensitive than the Mini-Mental State Examination (MMSE) for detecting mild cognitive deficits; (2) the use of education-appropriate cognitive screening instruments, with the MoCA-Basic administered to participants with limited educational attainment or illiteracy to reduce the influence of education on cognitive screening performance; (3) quantitative carotid plaque scoring, allowing assessment of plaque burden rather than simple plaque presence or absence; (4) concurrent assessment of a hemodynamic marker (ICA RI), providing complementary structural and hemodynamic information; and (5) inclusion of community-dwelling Egyptian adults aged ≥ 60 years, an understudied population that expands the evidence on carotid atherosclerosis and cognitive function in Middle Eastern and North African populations.

Several limitations temper inference. First, the cross-sectional design precludes causal inference and temporal sequencing; plaque burden and elevated RI may be markers rather than drivers of cognitive decline. Second, cognitive impairment was classified using MoCA-based screening instruments rather than comprehensive clinical and neuropsychological assessment. Although education-appropriate cognitive screening instruments were used and educational attainment was adjusted for in the multivariable models, residual confounding related to education and cognitive reserve, as well as some degree of misclassification, cannot be excluded. Third, brain MRI was not routinely performed because the study included community-dwelling older adults without known neurological disease. Consequently, intracranial atherosclerosis, silent cerebrovascular lesions, and white matter changes could not be evaluated and may have influenced the observed associations. Fourth, single-center recruitment may limit generalizability to populations with different demographic or vascular risk profiles. Fifth, although ultrasound protocols were standardized, operator and measurement variability remain potential sources of error. From a research perspective, prospective longitudinal studies are warranted to determine whether progression of carotid plaque burden and persistent hemodynamic abnormalities are associated with subsequent cognitive decline and whether modification of vascular risk factors influences these associations.