Our main finding is that LEAD is associated with cognitive decline regardless of age, gender and common vascular risk factors. The mean MoCA score in the LEAD group was below 26 points what indicates cognitive impairment. The main differences between the study and the control group were noticed in attention, visuospatial/executive, delayed recall, visual memory and learning. These cognitive domains are often affected in cognitive impairment of vascular origin.
As a marker of generalized atherosclerosis, LEAD leads not only to intermittent claudication and symptoms related to lower extremities but also increase the risk of cardiovascular events including cardiovascular deaths [4,5,6]. In addition, previously published studies also suggest that patients with LEAD perform worse in neuropsychological evaluation then the healthy patients [7,8,9,10,11].
One large population study in China, the “APAC study” , found that a low ABI (below 0.9) is directly related to poorer neuropsychological test scores. 3048 people with no history of stroke were selected in this study. MMSE was performed in each patient and the ankle-brachial index was measured. Reduced ABI was found in 161 people (5.28%), and cognitive impairment in 154 (5.05%). After performing regression models, it was proved that people with a lowered ABI have a higher risk of cognitive disorders. This correlation was independent of age, gender, education level, or other risk factors for vascular disease. This study showed a correlation between LEAD and cognitive impairment in the Asian population. But their findings do not necessarily apply to white populations, and more research is needed.
Not only the low level of ABI correlates with cognitive functions. In a cross-sectional study , it was found that endothelial abnormalities, increased vascular stiffness and microcirculation disorders negatively affects cognitive functions in older population measured by the CANTAB test.
There is a growing body of published research documenting the relationship between cognitive impairment and LEAD. However, the nature of this association remains unclear. One possible explanation is that LEAD is a marker of general atherosclerosis, including cerebral artery disease. Asymptomatic carotid and cerebral atherosclerosis may cause silent infarcts and contribute to cognitive impairment in this mechanism. In our study, only people without carotid artery stenosis were enrolled in the study, and adjustment for cardiovascular disease and vascular risk factors did not change the significance of this correlation. Another possible explanation is that a patient with LEAD may experience subcortical white matter lesions that are also silent. In the Rotterdam Study , the mean ABI was significantly lower in people with white matter lesions than in those without. White matter lesions are associated with cognitive decline, and cognitive impairment can be explained by this mechanism [15,16,17].
Nevertheless, the link between white matter lesions and ABI is not that well established. In another study  with the use of MRI, the researchers found that the low level of ABI was associated with poorer cognitive functions, irrespective of concomitant cardiovascular risk factors. However, there was no such correlation between low ABI and changes in white matter, volume of brain tissue, or ischemic changes. This evidence shows that there might exist other than general atherosclerosis pathways leading to cognitive impairment in patients with peripheral artery disease and further research is needed.
In our follow-up study, no cognitive changes were found despite adequate restoration of blood flow in the lower extremities and an increase in ABI. This indicates that the poor results in neuropsychological assessment were not correlated with suffering from the LEAD symptom, but the cause is more complex.
Previously published studies used MMSE as a cognitive tool. It is worth notice that MMSE has several limitations because visuospatial/executive functions are not thoroughly tested. These functions are frequently impaired in cognitive impairment of vascular origin . In our study, we use MoCA test. A systematic review showed that the MoCA test outperformed the MMSE test in distinguishing patients with and without cognitive impairment .
Our data suggest that LEAD is strongly associated with cognitive impairment. This opens up the possibilities of taking actions to prevent or delayed this disease. In patients with LEAD, the use of secondary prevention, which is appropriate drug therapy and rehabilitation, will not only reduce the number of adverse events of the lower extremities, but may also lead to the maintenance of normal cognitive functions [21, 22].
The sample of this study was relatively low which was a major limitation to the study. Moreover, we did not perform any type the neuroimaging so it was impossible to examine the pathological background. However, the LEAD was diagnosed not only by indirect way with ABI but each patient had arterial imagining.