The Vanderbilt Memory & Aging Project: Study Design and Baseline Cohort Overview

Article type: Research Article

Authors: Jefferson, Angela L.^{a; *} | Gifford, Katherine A.^a | Acosta, Lealani Mae Y.^a | Bell, Susan P.^{a; b; c} | Donahue, Manus J.^{d; e} | Davis, L. Taylor^e | Gottlieb, JoAnn^f | Gupta, Deepak K.^b | Hohman, Timothy J.^a | Lane, Elizabeth M.^a | Libon, David J.^g | Mendes, Lisa A.^b | Niswender, Kevin^h | Pechman, Kimberly R.^a | Rane, Swatiⁱ | Ruberg, Frederick L.^{j; k} | Su, Yan Ru^b | Zetterberg, Henrik^{l; m} | Liu, Dandanⁿ

Affiliations: [a] Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA | [b] Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA | [c] Center for Quality Aging, Division of General Internal Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA | [d] Department of Neurology, Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA | [e] Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA | [f] Vanderbilt Institute for Clinical & Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA | [g] Rowan University - School of Osteopathic Medicine, Department of Geriatrics and Gerontology, New Jersey Institute for Successful Aging, Stratford, NJ, USA | [h] Tennessee Valley Healthcare System, Division of Diabetes, Endocrinology, & Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA | [i] Radiology, University of Washington Medical Center, Seattle, WA, USA | [j] Boston University School of Medicine, Boston, MA, USA | [k] Section of Cardiovascular Medicine, Boston Medical Center, Boston, MA, USA | [l] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden | [m] Deparment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK | [n] Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

Correspondence: [*] Correspondence to: Angela L. Jefferson, PhD, Vanderbilt Memory & Alzheimer’s Center, 1207 17th Avenue South, Suite 204, Nashville, TN 37212, USA. Tel.: 615 322 8676; Fax: 615 875 2727; E-mail: [email protected].

Abstract: Background: Vascular health factors frequently co-occur with Alzheimer’s disease (AD). A better understanding of how systemic vascular and cerebrovascular health intersects with clinical and pathological AD may inform prevention and treatment opportunities. Objective:To establish the Vanderbilt Memory & Aging Project, a case-control longitudinal study investigating vascular health and brain aging, and describe baseline methodology and participant characteristics. Methods: From September 2012 to November 2014, 335 participants age 60– 92 were enrolled, including 168 individuals with mild cognitive impairment (MCI, 73±8 years, 41% female) and 167 age-, sex-, and race-matched cognitively normal controls (NC, 72±7 years, 41% female). At baseline, participants completed a physical and frailty examination, fasting blood draw, neuropsychological assessment, echocardiogram, cardiac MRI, and brain MRI. A subset underwent 24-hour ambulatory blood pressure monitoring and lumbar puncture for cerebrospinal fluid (CSF) collection. Results: As designed, participant groups were comparable for age (p = 0.31), sex (p = 0.95), and race (p = 0.65). MCI participants had greater Framingham Stroke Risk Profile scores (p = 0.008), systolic blood pressure values (p = 0.008), and history of left ventricular hypertrophy (p = 0.04) than NC participants. As expected, MCI participants performed worse on all neuropsychological measures (p-values < 0.001), were more likely to be APOE ɛ4 carriers (p = 0.02), and had enhanced CSF biomarkers, including lower Aβ42 (p = 0.02), higher total tau (p = 0.004), and higher p-tau (p = 0.02) compared to NC participants. Conclusion:Diverse sources of baseline and longitudinal data will provide rich opportunities to investigate pathways linking vascular and cerebrovascular health, clinical and pathological AD, and neurodegeneration contributing to novel strategies to delay or prevent cognitive decline.

Keywords: Alzheimer’s disease, biomarkers, brain MRI, cardiac MRI, mild cognitive impairment, vascular risk factors

DOI: 10.3233/JAD-150914

Journal: Journal of Alzheimer's Disease, vol. 52, no. 2, pp. 539-559, 2016