Objective: To determine whether extracranial carotid atherosclerotic disease (ECAD) is associated with increased key neurodegenerative pathology such as neurofibrillary tangle (NFT), beta-amyloid plaque or cerebral amyloid angiopathy (CAA) accumulation, findings associated with Alzheimer's disease (AD) and other dementias.

Methods: Our prospective longitudinal clinicopathological study, the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program, records the presence or absence of clinically-diagnosed ECAD and does semi-quantitative density estimates of NFT, beta amyloid plaques and CAA at death. After adjusting for potential confounding factors determined by logistic regression analysis, histopathology density scores were evaluated in individuals with ECAD (n=66) and individuals without ECAD (n=125).

Results: We found that the presence of ECAD is associated with a 21% greater NFT burden at death compared to no ECAD (P=.02). Anatomically, increased NFT burden was seen throughout the brain regions evaluated but was only significant in the temporal lobe (P <.05) and the entorhinal cortex (P=.02). Complimentary to this finding, we found that subjects with carotid endarterectomy (CEA), the surgical treatment of ECAD (n=32), had decreased NFT densities compared to those who had ECAD without CEA (n=66) (P=.04). In contrast to NFT, we found that ECAD was not associated with beta-amyloid plaque or CAA density.

Conclusion: These findings indicate that ECAD is associated with NFT burden in the temporal lobe and entorhinal cortex, which has clinical significance for AD and non-AD dementias and cognitive dysfunction. Further understanding of whether ECAD increases risk for neurodegenerative brain changes is highly relevant because ECAD is a treatable disease that is otherwise not evaluated for or specifically treated as a dementia risk factor.