Using various imaging techniques, it is possible to assess markers of pre-clinical large vessel disease. Intima media thickness (IMT) and carotid plaque are measures of atherosclerosis in the carotid artery, which can be obtained via ultrasonography. Both IMT and carotid plaque are more prevalent in patients with dementia and AD than in cognitively healthy individuals [
41]. Moreover, both measures are related to increased cognitive decline in patients with AD [
42]. Additionally, several population-based studies have shown that individuals with the highest IMT measures have an increased risk of incident dementia, including AD [
32],[
43],[
44]. Carotid plaque scores were also associated with an increased risk of AD in one study, but this association lacked statistical significance [
44]. Another marker of pre-clinical large vessel disease is calcification volume in the atherosclerotic plaque, which can be assessed using computed tomography (CT). Although calcification is only part of the plaque, it is a suitable measure of the underlying plaque burden [
45]. CT has the disadvantage of radiation exposure, but CT measures of atherosclerotic calcification are more observer-independent than ultrasonography measures. Few studies have investigated the relation between CT-derived atherosclerotic calcification and dementia, but some studies found that larger calcification volumes in the coronary arteries, aortic arch, and carotid arteries relate to worse cognitive performance [
46],[
47]. Moreover, larger calcification volume was associated with smaller brain tissue volumes and worse microstructural integrity of the white matter, which are both factors related to an increased risk of AD [
46]. Mechanisms linking carotid large vessel disease to AD include sub-clinical cerebral small vessel disease (see below), hypoperfusion, or shared etiology [
3],[
4],[
6].