Carotid Arteries in Cerebral Small Vessel Disease and Dementia

Carotid artery disease (CAD) is a recognised important cause of stroke. However, the relationship between CAD and cerebral small vessel disease (SVD) and dementia remains unclear. We hypothesized that CAD in older individuals significantly affects cerebral perfusion, and leadsto cerebral SVD. We performed a clinicopathological study in patients from the Cognitive Function After Stroke (CogFAST) study and prospectively recruited patients with various dementia diagnoses and evidence of cerebral SVD. In addition to brain tissues, we collected postmortem samples of the internal carotid arteries (ICA) from these cohorts in the Newcastle Brain Tissue Resource. Standard neuropathological examination was performed for diagnosis and assignment of the cases per current diagnostic criteria for vascular and neurodegenerative dementias, which were assessed for the presence of vascular pathology including the degree of stenosis and sclerosis in vascular tissues. We evaluated a total of 159 ICA samples and brain tissues from all cases with evidence of SVD. Severity of ICA stenosis and sclerotic index correlated strongly with both clinical stroke and brain infarction (F15, df 135, P<0.001 ). More than 90% of the subjects had one subtype of ICA lesion in the order: intimal thickening >fibrocalcific >fibrous cap (thick) >fibrous cap (thin) >thrombus group with a strong inflammatory reaction in fibrocalcific atheromas. Linear regression analysis showed that ICA stenosis was positively correlated to both SVD pathology scores and total number of vascular lesions (r=0.34, 95% CI 0.18-0.49, P<0.034) . We found that severity of stenosis was related to anterior circulation involvement and small infarcts in the subcortical structures including the white matter (WM) rather than the cortex. Total intracranial artery scores were correlated with ICA stenosis and sclerosis (r=0.43, 95% CI 0.26-0.56, P<0.001 ). In the CogFAST group analysis, the smallest lesions in the WM but not in the cortex or basal ganglia and thalamus were associated with severity of ICA stenosis (r=0.42, 95% CI 0.27-0.56, P <0.05). Carotid atherosclerosis promotes cerebral SVD types of change and influences the cerebral arterial system. Our observations also suggest extracranial ICA pathology impacts on the perfusion and integrity of the deep WM.