Grant supports Research on Abnormal Brain Aging

With the aid of an $18.2 million, five-year grant renewal from the National Institute on Aging, the Vanderbilt Memory and Aging Project (VMAP) will advance interdisciplinary research into abnormal brain aging and cognitive decline in older adults, with continuing emphasis on the role of blood flow changes in the heart and brain.

Growing evidence suggests modest age-related changes in cardiovascular and cerebrovascular health, which might not typically be seen by clinicians as a warning sign, can be precursors of cognitive decline, Alzheimer’s disease and other forms of dementia.

“For decades, Alzheimer’s research has focused on the important role of two protein abnormalities, amyloid plaques and tau tangles. However, evidence from VMAP has shown that memory loss and cognitive decline in aging reflects much more complex disease processes. Vascular health may be an essential component of preventing Alzheimer’s disease and the devastating memory loss that accompanies it,” said the project’s principal investigator, Angela Jefferson, PhD, professor of Neurology and director of the Vanderbilt Memory and Alzheimer’s Center.

According to the World Health Organization, some 50 million people worldwide have dementia, and Alzheimer’s may contribute to 60-70% of cases. There is no cure for Alzheimer’s and no proven method of prevention.

“This significant grant renewal will help Vanderbilt University Medical Center advance a promising area of discovery as we continue to expand our research and clinical efforts in the field of Alzheimer’s and dementia,” said Dane Chetkovich, MD, PhD, Margaret and John Warner Professor and chair of Neurology.

Following its launch in 2012, VMAP recruited 336 study participants ages 60 and over who agreed to undergo evaluation every 18 to 24 months. At recruitment, half of the participants were cognitively normal, and half had mild cognitive impairment, a clinical syndrome thought to reflect the earliest stage of Alzheimer’s disease or dementia. The grant renewal, along with a $4.4 million grant awarded to VMAP co-investigator Katherine Gifford, PsyD, will help VMAP expand and diversify this research cohort.

“These new funding sources will support increasing our current participant base to 900 participants with a focus on recruiting more people from racial groups that have historically been underrepresented in Alzheimer’s research. This expansion will make VMAP the largest study of its kind in the aging neuroscience space with detailed cardiovascular, cerebrovascular and Alzheimer’s disease biomarker assessments,” Jefferson said.

Assessments include a physical examination, a blood draw, memory testing, a brain MRI, a heart MRI, echocardiogram and lumbar puncture for cerebrospinal fluid sampling. Participants are also encouraged to join the optional brain PET study and brain autopsy program.

The project has supported numerous training grants for early career scientists. Among the project’s higher profile findings to date:

Older people who have suboptimal blood flow from their hearts also have blood flow reductions in the temporal lobe regions of the brain where Alzheimer’s pathology first begins;

In brain MRIs in older adults, fluid-filled spaces around cerebral small vessels are associated with compromised cognitive abilities;

Greater stiffness of the aorta, the body’s main artery from the heart, is associated with lower cerebral blood flow and may play a role in cognitive decline.

The Vanderbilt Memory and Alzheimer’s Center encourages anyone age 50 or older who is interested in joining the study to visit the center’s website to learn more about how to get involved. Test results are reported to participants, including any incidental findings that may be clinically significant. Exclusion criteria for the study include a history of major psychiatric illness or head injury with loss of consciousness.

Jefferson has a dozen co-investigators in VMAP who hail from departments across the Vanderbilt campus, including Neurology, Radiology and Radiological Sciences, Medicine, Chemistry, Electrical Engineering and Biostatistics.

VMAP is supported by National Institute on Aging grants AG034962 and AG062826.

“The Alzheimer’s Association has long recognized the vascular contributions to Alzheimer’s disease,” said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer. “We are proud to have supported Dr. Jefferson’s early and promising work in this space that has led to significant follow-on funding from the National Institute on Aging.”