The role of cerebral microinfarcts in mixed Alzheimer’s and vascular pathology: implications for cognitive impairment

Abstract Background Alzheimer’s disease (AD) and vascular dementia (VaD) are the two leading causes of cognitive decline, with mixed dementia increasingly recognized as a common and clinically significant disease in the aging population. While the amyloid hypothesis traditionally defines AD, autopsy data increasingly reveal mixed dementia where AD pathology coexists with vascular lesions, particularly cerebral microinfarcts (CMIs). Objective This review investigates the role of CMIs as a critical mechanistic link between cerebrovascular disease (CVD) and neurodegeneration, particularly in the development of mixed dementia and progressive cognitive impairment. Methods A narrative review of published studies was conducted in PubMed/MEDLINE, ScienceDirect and Google Scholar (2015–2025). Based on defined inclusion/exclusion criteria, 101 full-text articles spanning high-field neuroimaging (3T/7T MRI, Neurite Orientation Dispersion and Density Imaging (NODDI)), fluid biomarkers and clinicopathological autopsy series were used to evaluate the mechanisms of microvascular injury, diagnostic performance and cognitive outcomes in mixed Alzheimer’s and vascular pathology. Results CMIs are significantly more prevalent in patients with dementia (57%) than in nondementia patients (31%). These lesions can independently accelerate cognitive decline across domains such as episodic memory and executive function. This review highlights a synergistic effect in which the combination of AD markers (plaques and tangles) and CMIs lowers the threshold of the brain for clinical dementia more than either pathology alone does. Cortical microinfarcts are often linked to amyloid angiopathy, which has the strongest correlation with cognitive impairments. Conclusion CMIs are vital contributors to mixed dementia. Addressing this detection gap in clinical imaging is essential for early diagnosis. Future strategies must integrate lifestyle interventions and aggressive management of vascular risk factors (VRFs), supported by evidence from the Livingston Commission and FINGER trial alongside traditional AD treatments, to mitigate the progression of the global pandemic effectively.