Vanderbilt Memory and Aging Project

Alzheimer Disease Clinical Trial

— VMAP  

Official title:

Vanderbilt Memory and Aging Project

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05372159
• Other study ID #: 120158
• Secondary ID: K23AG045966R01AG
• Status: Recruiting
• Start date: September 17, 2012
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2023
• Source: Vanderbilt University Medical Center
• Contact: Michelle Houston
• Phone: 6153228676
• Email: michelle.houston[@]vumc.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aged, 80 and Over
• Aging
• Alzheimer Disease
• Biomarkers
• Brain
• Cognitive Dysfunction
• Neuropsychological Tests

Intervention

Other:
• none, observational study
none, observational study

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	White matter hyperintensities Volume	White matter lesion volume measured by FLAIR imaging modality	baseline to year five
Primary	Grey Matter Volume	Grey matter volume measured by T1 imaging modality	baseline to year five
Primary	Cerebral Blood Flow	Resting cerebral blood flow to brain regions measured by T3 perfusion	baseline to year five
Primary	Lacunar infarcts	Number of lacunar infarcts measured by MRI	baseline to year five
Primary	Small vessel microbleeds	Presence and number of microbleeds measured by MRI	baseline to year five
Primary	Left ventricular ejection fraction	Left ventricular ejection fraction measured by echocardiogram	baseline to year five
Primary	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
Primary	Cardiac stroke volume	Stroke volume measured by echocardiogram	baseline to year five
Primary	Pulse Wave velocity	pulse wave velocity measured by cardiac MRI	baseline to year five
Primary	Cardiac Strain	Global longitudinal strain and global circumferential strain measured by cardiac MRI	baseline to year five
Primary	Biological marker for Alzheimer's disease	Tau, amyloid, neurodegenerative levels measured in cerebrospinal fluid samples	baseline to year five
Primary	Blood based biological marker for Alzheimer's disease	Tau, amyloid, neurodegenerative levels measured in blood samples	baseline to year five
Primary	APOE Genotype	APOE e4 allele status	baseline to year five