Midlife Neuropsychological Profiles and Associated Vascular Risk: The Bogalusa Heart Study

Article type: Research Article

Authors: De Anda-Duran, Ileana^{a; *} | Kolachalama, Vijaya B.^{b; c} | Carmichael, Owen T.^d | Hwang, Phillip H.^e | Fernandez, Camilo^a | Au, Rhoda^{f; g} | Bazzano, Lydia A.^a | Libon, David J.^{h; i}

Affiliations: [a] Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA | [b] Department of Medicine, Boston University School of Medicine, Boston, MA, USA | [c] Department of Computer Science and Faculty of Computing & Data Sciences, Boston University, Boston, MA, USA | [d] Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge, LA, USA | [e] Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA | [f] Boston University Alzheimer’s Disease Center, Boston, MA, USA | [g] Department of Internal Medicine, Ochsner Health System, New Orleans, LA, USA | [h] Department of Psychology, Rowan University, Glassboro, NJ, USA | [i] New Jersey Institute for Successful Aging, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA

Correspondence: [*] Correspondence to: Ileana De Anda-Duran, MD, MPH, Epidemiology Department, Tulane University, School of Public Health and Tropical Medicine, 1440 Canal St. Ste. 2036, New Orleans, LA 70112, USA. Tel.: +1 (504)988-7143; E-mail: ideandaduran@tulane.edu.

Abstract: Background:Individuals with Alzheimer’s disease (AD) often present with coexisting vascular pathology that is expressed to different degrees and can lead to clinical heterogeneity. Objective:To examine the utility of unsupervised statistical clustering approaches in identifying neuropsychological (NP) test performance subtypes that closely correlate with carotid intima-media thickness (cIMT) in midlife. Methods:A hierarchical agglomerative and k-means clustering analysis based on NP scores (standardized for age, sex, and race) was conducted among 1,203 participants (age 48±5.3 years) from the Bogalusa Heart Study. Regression models assessed the association between cIMT ≥50th percentile and NP profiles, and global cognitive score (GCS) tertiles for sensitivity analysis. Results:Three NP profiles were identified: Mixed-low performance [16%, n = 192], scores ≥1 SD below the mean on immediate, delayed free recall, recognition verbal memory, and information processing; Average [59%, n = 704]; and Optimal [26%, n = 307] NP performance. Participants with greater cIMT were more likely to have a Mixed-low profile [OR = 3.10, 95% CI (2.13, 4.53), p < 0.001] compared to Optimal. After adjusting for education and cardiovascular (CV) risks, results remained. The association with GCS tertiles was more attenuated [lowest (34%, n = 407) versus highest (33%, n = 403) tertile: adjusted OR = 1.66, 95% CI (1.07, 2.60), p = 0.024]. Conclusion:As early as midlife, individuals with higher subclinical atherosclerosis were more likely to be in the Mixed-low profile, underscoring the potential malignancy of CV risk as related to NP test performance, suggesting that classification approaches may aid in identifying those at risk for AD/vascular dementia spectrum illness.

Keywords: Alzheimer’s disease, atherosclerosis, cognition, midlife, neuropsychological subtyping, vascular risk

DOI: 10.3233/JAD-220931

Journal: Journal of Alzheimer's Disease, vol. 94, no. 1, pp. 101-113, 2023