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

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 APOEɛ4 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.

Fig. 1

Participant Inclusion/Exclusion Details. *Exclusion categories delineated on the right side of the figure are not mutually exclusive. Specifically, of the 9 participants assigned to more than one category, 8 were included in Neuropsychological Profile Inconsistent with MCI or NC and in at least one other category (i.e., 2 in MRI Contraindication, 3 in Presence of Major Psychiatric Disorder, 2 in No Reliable Study Partner Available, and one in History of Neurological Disorder). Another participant was categorized both in Met Criteria for NC but no MCI Match and MRI Contraindication.

Fig. 2

Vessel-Encoded pseudo-Continuous Arterial Spin Labeling. The white arrow illustrates a region of decreased cerebral blood flow.

Fig. 3

Magnetic Resonance Angiography. Illustration of a complete (A) and incomplete (B) Circle of Willis.

Fig. 4

Vessel Wall Imaging. The dashed line illustrates measurement of the outer diameter of the vessel wall and the solid line illustrates measurement of the inner diameter of the vessel wall. The diameters are reported as inner/outer for each vessel as follows: (A) middle cerebral artery, 2.84/3.73 mm, (B) anterior cerebral artery 2.19/3.31 mm, and (C) internal carotid artery 3.67/4.90 mm.