Carotid Artery Atherosclerosis, MRI-defined Structural Brain Abnormalities, and Cognitive Performance in Elderly American Indians: The Strong Heart Study

Tauqeer Ali^1*Dedra Buchwald²Dean Shibata³Mary J Roman⁴Steven Verney⁵Barbara V Howard⁶Jason Gari Umans⁶Shelley Cole⁷Cynthia West⁶Ying Zhang⁸Jessica Reese⁸Dorothy A Rhoades⁹Marcia O'leary¹⁰W T Longstreth¹¹Amanda Fretts¹²Astrid Suchy-Dicey¹³

• ¹Department of Biostatistics and Epidemiology, Center for American Indian Health Research, Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, United States
• ²Neurosciences Institute, Department of Neurological Surgery, UW Medicine, University of Washington, Seattle, United States
• ³Department of Radiology, University of Washington, Seattle, United States
• ⁴Weill Cornell Medicine, New York, United States
• ⁵Department of Psychology, The University of New Mexico, Albuquerque, United States
• ⁶MedStar Research Institute, Hyattsville, United States
• ⁷Texas Biomedical Research Institute, San Antonio, United States
• ⁸Department of Biostatistics and Epidemiology, Center for American Indian Health Research, Hudson College of Public Health, The University of Oklahoma Health Sciences, Oklahoma City, United States
• ⁹Department of Medicine, College of Medicine, The University of Oklahoma Health Sciences, Oklahoma City, United States
• ¹⁰Missouri Breaks Industries Research Inc, Eagle Butte, United States
• ¹¹Department of Neurology, University of Washington, Seattle, United States
• ¹²Department of Epidemiology, School of Public Health, University of Washington, Seattle, United States
• ¹³Boston University School of Medicine, Slone Epidemiology Center, Boston, United States

Background and Objective: American Indian populations face disproportionately high rates of atherosclerotic cardiovascular disease (CVD), yet the potential consequences of mid-life carotid atherosclerosis on brain health and cognition later in life remain poorly understood. This study addresses a critical knowledge gap by evaluating whether subclinical carotid atherosclerosis in midlife is associated with later-life structural brain abnormalities and cognitive performance in a large cohort of American Indian adults from the Strong Heart Study. This is the first investigation to explore these associations in this underserved and understudied population, using longitudinal data with vascular, neuroimaging, and cognitive measures. Methods: A total of 783 participants (mean age 59.9 years) underwent carotid ultrasonography between 1998 and 1999 to assess intima-media thickness and plaque. Between 2010 and 2013, participants received brain magnetic resonance imaging to assess infarcts, hemorrhages, white matter lesions, and brain atrophy. Cognitive function was also evaluated during this period. Multivariable regression models adjusted for sociodemographic, behavioral, and clinical CVD risk factors were used to assess associations. Results: Greater intima-media thickness was associated with more severe sulcal widening, and presence and extent of plaque were associated with poorer verbal fluency; both findings remained significant after adjustment for sociodemographic, behavioral, and clinical risk factors. No significant associations were observed between carotid measures and the presence of infarcts, hemorrhages, or white matter lesions. Conclusion: These findings suggest that subclinical carotid atherosclerosis in midlife may contribute to later-life brain atrophy and cognitive vulnerability, particularly in verbal fluency, among American Indians.