Vanderbilt Memory and Aging Project

NCT ID: NCT05372159

Last Updated: 2025-08-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-09-17

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Alzheimer Disease Aging Aged, 80 and Over Biomarkers Brain Case-Control Studies Cognitive Dysfunction Neuropsychological Tests

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

none, observational study

Intervention Type OTHER

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.

none, observational study

Intervention Type OTHER

none, observational study

Interventions

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none, observational study

none, observational study

Intervention Type OTHER

Eligibility Criteria

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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
* 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.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Angela Jefferson

Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Angela Jefferson, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

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Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Mallory Rockwell

Role: CONTACT

6153228676

Facility Contacts

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Paige Crepezzi

Role: primary

615-322-8676

Other Identifiers

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K23AG045966

Identifier Type: NIH

Identifier Source: secondary_id

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R01AG034962

Identifier Type: NIH

Identifier Source: secondary_id

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F32AG046093

Identifier Type: NIH

Identifier Source: secondary_id

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K24AG046373

Identifier Type: NIH

Identifier Source: secondary_id

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R01NS100980

Identifier Type: NIH

Identifier Source: secondary_id

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R01AG056534

Identifier Type: NIH

Identifier Source: secondary_id

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F32AG058395

Identifier Type: NIH

Identifier Source: secondary_id

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F31AG066358

Identifier Type: NIH

Identifier Source: secondary_id

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IIRG-08-8873

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

120158

Identifier Type: -

Identifier Source: org_study_id

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