Vanderbilt Memory and Aging Project (VMAP)

This study will use an observational cohort to cross-sectionally and longitudinally relate vascular health to clinical, imaging, and biological markers of early Alzheimer's disease and cerebrovascular disease among aging adults. Adjusting for relevant clinical covariates, we will test the hypothesis that vascular health is associated with clinical, brain magnetic resonance imaging (MRI), neuropsychological, and cerebrospinal fluid markers of early cerebrovascular and Alzheimer's disease changes (i.e., prior to the onset of significant cognitive decline or dementia). Secondarily, we will examine medical and genetic factors that might mediate associations between vascular health and brain aging, such as inflammatory processes, insulin resistance, and genetic factors (e.g., APOE, a susceptibility risk factor for dementia). Findings will advance knowledge regarding the role that vascular health plays in brain aging.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Dysfunction; Alzheimer Disease; Aging; Biomarkers; Brain; Aged, 80 and Over; Case-Control Studies; Neuropsychological Tests
• Intervention / Treatment: Other: none, observational study

Detailed Description

As the population ages, Alzheimer's disease and dementia are becoming a public health crisis. In the initial cycle, the Vanderbilt Memory & Aging Project was established to examine cardiovascular function in relation to structural neuroimaging changes and cognition. The investigators tested whether associations were more prominent in clinically symptomatic individuals. The investigators successfully enrolled several hundred participants age 60 and older, data successfully supported multiple training grant opportunities (e.g., National Research Service Awards, Career Development Awards), and the investigators published numerous papers. The results suggest subclinical cardiovascular changes relate to worse cognition, white matter changes, and cerebral atrophy, especially in the hippocampus and other cortical regions primarily affected in Alzheimer's disease. Evidence to date supports the central hypothesis that well-established homeostatic mechanisms designed to protect cerebral blood supply become less effective with age, altering the integrity of cerebral hemodynamics, and lowering the threshold for neurodegenerative and cognitive changes. Interestingly, preliminary associations between subclinical cardiovascular integrity and cerebral hemodynamics are stronger among carriers of the apolipoprotein E ε4 (APOE-ε4) allele, an Alzheimer's disease genetic risk factor. Furthermore, findings are more prominent in cognitively unimpaired participants, suggesting subtle cardiac hemodynamic changes may act as an underrecognized precipitating contributor of neurodegeneration and corresponding cognitive decline, distinct from the exacerbating effects of overt cerebrovascular disease. In the next cycle, the investigators propose to better characterize underlying mechanisms linking early cardiac hemodynamic changes to abnormal brain aging in cognitively unimpaired participants, and test whether APOE-ε4 moderates the effect of vascular damage on brain health. The investigators will follow the existing cohort and supplement it with enrollment of several hundred cognitively unimpaired participants to increase statistical power for more comprehensive analyses. The new participants will complete serial longitudinal assessments with identical procedures plus lumbar puncture for cerebrospinal fluid acquisition. Innovative translational efforts leveraging sophisticated neuroimaging and molecular biomarkers are critical to better detect early, asymptomatic cardiac hemodynamic changes, which may be more influential in initiating downstream cerebrovascular and neurodegenerative processes than previously recognized.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Mallory Rockwell; Phone Number: 6153228676; Email: mallory.rockwell@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Paige Crepezzi; Phone Number: 615-322-8676

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Community-dwelling older adults.

Description

Inclusion Criteria:

• Participants recruited will include 1,000 adults age 50 and older.
• After the eligibility visit, a small portion of participants (~150) enrolling must meet diagnostic criteria for mild cognitive impairment according to a clinician diagnosis and/or medical records (i.e., participants must have mild memory or cognitive problems, but they must be free of any functional problems and not have Alzheimer's disease or another form of dementia). The remaining ~850 participants will be cognitively unimpaired adults age 50 and older.
• Because the neuropsychological tests used to measure cognitive performance are validated on English-speaking populations, we require that English be the primary language of all participants.

Exclusion Criteria:

• No available reliable study partner
• History of major psychiatric illness (e.g., schizophrenia, bipolar), neurological illness (e.g., stroke, epilepsy, multiple sclerosis, Parkinson's disease, dementia), or head injury with significant loss of consciousness. These exclusion criteria have been applied because they affect brain structure and function.
• Diagnosis of congestive heart failure
• Diagnosis of atrial fibrillation or other heart arrhythmia
• Diagnosis of Chronic obstructive pulmonary disease
• Diagnosis of cancer (current)
• History of serious alcohol or drug abuse (past or current)
• Participants unable to undergo MRI will be excluded. Reasons may include: a. Subjects who have any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc.). b. Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced. c. Subjects who have cerebral aneurysm clips. d. Subjects who may have shrapnel imbedded in their bodies (e.g., from war wounds), metal workers and machinists (e.g., potential for metallic fragments in or near the eyes). e. Subjects who are pregnant. Given that the minimum age of recruitment for the current study is 50 years of age, it is unlikely that prospective participants will be excluded because of pregnancy. f. Subjects who have excessive amounts of metal dental work based on records released by their dentist.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cognitively healthy adults; Eligible participants completed a 4-hour screening visit, and a consensus team determined cognitive status according to the National Institute on Aging and Alzheimer's Association Workgroup guidelines.	Other: none, observational study; none, observational study
Cognitively impaired adults; Eligible participants completed a 4-hour screening visit, and a consensus team determined cognitive status according to the National Institute on Aging and Alzheimer's Association Workgroup guidelines.	Other: none, observational study; none, observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
White matter hyperintensities Volume	White matter lesion volume measured by FLAIR imaging modality	baseline to year five
Grey Matter Volume	Grey matter volume measured by T1 imaging modality	baseline to year five
Cerebral Blood Flow	Resting cerebral blood flow to brain regions measured by T3 perfusion	baseline to year five
Lacunar infarcts	Number of lacunar infarcts measured by MRI	baseline to year five
Small vessel microbleeds	Presence and number of microbleeds measured by MRI	baseline to year five
Left ventricular ejection fraction	Left ventricular ejection fraction measured by echocardiogram	baseline to year five
Cardiac output	Amount of blood the heart pumps from each ventricle per minute, litres per minute (L/min). Measured by echocardiogram	baseline to year five
Cardiac stroke volume	Stroke volume measured by echocardiogram	baseline to year five
Pulse Wave velocity	pulse wave velocity measured by cardiac MRI	baseline to year five
Cardiac Strain	Global longitudinal strain and global circumferential strain measured by cardiac MRI	baseline to year five
Biological marker for Alzheimer's disease	Tau, amyloid, neurodegenerative levels measured in cerebrospinal fluid samples	baseline to year five
Blood based biological marker for Alzheimer's disease	Tau, amyloid, neurodegenerative levels measured in blood samples	baseline to year five
APOE Genotype	APOE e4 allele status	baseline to year five

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA)
• Investigators: Principal Investigator: Angela Jefferson, PhD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2012
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 12, 2022

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: biomarkers; Alzheimer's disease; mild cognitive impairment; cardiac MRI; brain MRI; vascular risk factors; longitudinal studies
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease
• Other Study ID Numbers: 120158; K23AG045966 (U.S. NIH Grant/Contract); R01AG034962 (U.S. NIH Grant/Contract); F32AG046093 (U.S. NIH Grant/Contract); K24AG046373 (U.S. NIH Grant/Contract); R01NS100980 (U.S. NIH Grant/Contract); R01AG056534 (U.S. NIH Grant/Contract); F32AG058395 (U.S. NIH Grant/Contract); F31AG066358 (U.S. NIH Grant/Contract); IIRG-08-8873 (Other Grant/Funding Number: Alzheimer's Association)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No