Introduction
Alzheimer’s disease (AD) is the most common form of dementia.1 As of 2022, 6.55 million people in the USA had AD alone.2 Non-Alzheimer’s dementias comprise a large group of dementias that include vascular, Lewy-Body, frontotemporal and other dementias.3 There is a growing appreciation that vascular disease and associated vascular risk factors contribute to dementia risk.4 5
Vascular contributions to cognitive impairment and dementia (VCID) encompass a broad group of systemic vascular processes impacting brain health.4–6 Research in VCID has predominantly focused on cerebral small vessel disease (cSVD)7 8 and vascular risk factors including age, hypertension (HTN), hyperlipidaemia (HLD) and smoking.2 8–10 In contrast to cSVD, extracranial carotid atherosclerotic disease (ECAD) is characterised by large vessel atherosclerosis at the common carotid artery bifurcation and the internal carotid artery, leading to arterial stenosis.
Emboli from ECAD can cause cerebrovascular accidents, which have immediate effects on brain tissue and cognition and are associated with a well-defined long-term risk for dementia.11 Patients with ECAD who have no recent history of stroke or transient ischaemic attack (TIA) attributed to ECAD are considered asymptomatic. The prevalence of asymptomatic ECAD (aECAD) is approximately 7.5% for moderate ECAD (defined as 50%–70% stenosis) and 3% for severe ECAD (>70% stenosis) in individuals over 60 years of age, with higher predominance in men.12 Current treatment for aECAD primarily focuses on managing comorbidities (eg, smoking, HTN, HLD and diabetes) and on stroke prevention.13 However, there is no clinical evaluation or treatment goals targeting dementia outcomes. This is due to the lack of a well-established association between aECAD and dementia.
Few studies have focused on evaluating the impact of carotid disease on AD.14–20 Of these studies, five reported a positive association between carotid disease and AD,14–19 and one not confirming this association.20 Key limitations of these studies include (1) most rely on small cohorts; (2) use of non-clinical indicators of carotid atherosclerosis, such as carotid intima–media thickness ratio and common carotid plaque counting; (3) they do not control for cardiovascular confounders such as HTN, smoking, diabetes and heart disease and (4) inclusion of patients with both symptomatic and asymptomatic carotid disease. These studies, including the Rotterdam study,15 contributed significantly to the AD field by highlighting the importance of vascular disease and vascular risk factors in AD physiology. However, whether asymptomatic carotid stenosis is associated with AD and non-AD dementia risk remains unclear.
Defining the association between aECAD and AD as well as other forms of dementia is crucial considering the availability of effective treatments for aECAD that are currently not used for reducing the risk of AD and non-AD dementias. Furthermore, a deeper understanding of the cognitive effects of ECAD could inform clinical trials aimed at modifying the management of carotid disease. Cognition is a critical outcome to document in the aECAD population, as cognitive dysfunction results in increased disability, dependence, decreased medication adherence, higher healthcare costs and higher caregiving needs.2
This study evaluated the hypothesis that aECAD is associated with an elevated risk of AD and non-AD dementias leveraging longitudinal data with a US-based population insurance claims records.