Association of Carotid Intima Media Thickening with Future Brain Region Specific Amyloid-β Burden

Article type: Research Article

Authors: Baradaran, Hediyeh^{a; *} | Peloso, Gina M.^b | Polak, Joseph F.^c | Killiany, Ronald J.^{d; e} | Ghosh, Saptaparni^{d; f} | DeCarli, Charles S.^g | Thibault, Emma G.^h | Sperling, Reisa A.^{h; i} | Johnson, Keith A.^{h; i} | Beiser, Alexa^{b; d; f} | Romero, Jose R.^{d; f} | Seshadri, Sudha^{d; f; j}

Affiliations: [a] Department of Radiology, University of Utah, Salt Lake City, UT, USA | [b] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [c] Department of Radiology, Tufts University School of Medicine, Boston, MA, USA | [d] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [e] Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA | [f] NHLBI’s Framingham Heart Study, Framingham, MA, USA | [g] Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Davis, CA, USA | [h] Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [i] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [j] Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA

Correspondence: [*] Correspondence to: Hediyeh Baradaran, MD, 30 N 1900 E #1A141, Salt Lake City, UT 84135, USA. Tel.: +1 801 581 4916; Fax: +1 801 581 2414; E-mail: [email protected].

Abstract: Background:Carotid atherosclerosis is associated with cognitive impairment and dementia, though there is limited evidence of a direct link between carotid disease and amyloid-β (Aβ) burden. Objective:We studied the association of baseline and progressive carotid intima media thickness (CIMT) with Aβ on 11C-Pittsburgh Compound B (PiB) to determine if those with carotid atherosclerosis would have higher Aβ burden. Methods:We studied 47 participants from the Framingham Offspring cohort with carotid ultrasounds measuring CIMT at their 6th clinic examination (aged 49.5±5.7 years) and an average of 9.6 years later, and PiB imaging measuring Aβ on average 22.1 years post baseline. We used multivariate linear regression analyses to relate baseline, follow-up, mean, and progression of internal carotid artery (ICA) and common carotid artery (CCA) CIMT to Aβ in brain regions associated with Alzheimer’s disease (AD) and related dementias (ADRD), adjusting for age, sex, and other vascular risk factors. Results:Participants with higher mean ICA IMT had more Aβ in the precuneus (beta±standard error [β±SE]: 0.466±0.171 mm, p = 0.01) and the frontal, lateral, and retrosplenial regions (β±SE: 0.392±0.164 mm, p = 0.022) after adjusting for age, sex, vascular risk factors, and medication use. We did not find an association between any CCA IMT measures and Aβ or progression of ICA or CCA IMT and Aβ. Conclusion:Carotid atherosclerosis, as measured by ICA IMT, is associated with increased Aβ burden later in life. These findings support a link between vascular disease and AD/ADRD pathophysiology.

Keywords: Alzheimer’s disease, amyloid, carotid atherosclerosis, carotid ultrasound

DOI: 10.3233/JAD-215679

Journal: Journal of Alzheimer's Disease, vol. 89, no. 1, pp. 223-232, 2022