A new study conducted by Vanderbilt Kennedy Center faculty and through the Vanderbilt Center for Cognitive Medicine has found important differences in the brains of adults with Down syndrome that could help identify mechanisms of memory, learning, and attention loss during the development of Alzheimer’s disease. The study looked at a part of the brain’s communication system called the cholinergic system, which plays a key role in memory and thinking.
Using a specialized brain scan called PET imaging, researchers were able to measure the health of cholinergic nerve endings in the brain. These nerve endings help carry messages using a chemical called acetylcholine, which is known to be important for attention, learning, and memory. In Alzheimer’s disease, this system typically breaks down.
Surprisingly, the study found that adults with Down syndrome have a higher density of these cholinergic connections in several areas of the brain compared to people without Down syndrome. However, as they get older, their brain scans show a faster decline in these connections than in the general population. In addition, the study team found that the health of the brain cholinergic system declines as amyloid protein (elevated in Alzheimer’s disease) accumulates and as memory function declines, suggesting a link to developing Alzheimer’s disease.
Paul Newhouse, M.D.
“Most adults with Down syndrome develop signs of Alzheimer’s disease by the time they reach their 60s,” said Paul Newhouse, M.D., Jim Turner Professor of Cognitive Disorders and professor of Psychiatry & Behavioral Sciences, Pharmacology, and Medicine. “By studying how their brains change over time, we are gaining a clearer picture of how the disease progresses—and how we might intervene earlier. Our hope is that we will be able to develop new ways to protect memory and thinking skills for as long as possible.”
While more research is needed, this study could lead to earlier and more accurate detection of Alzheimer’s disease in people with Down syndrome. It also opens the door to new treatments that focus on protecting the brain’s cholinergic system.
“This study is a big step in the right direction,” said Newhouse. “And it was made possible thanks to the individuals with Down syndrome and their families who participated in the research.”
To learn more about this study and other research related to aging and Down syndrome, visit the Vanderbilt Center for Cognitive Medicine.
Also, Newhouse and his colleagues have had their research papers published in three journals. These papers provide more detailed information on the background, research methods, and results.
Russell JK, Conley AC, Boyd BD, Begnoche JP, Schlossberg R, Stranick A, Rosenberg A, Acosta LMY, Martin D, Neal Y, Kanel P, Albin RL, Rafii MS, Dumas J, Newhouse PA. Differences in cholinergic terminal density in adults with Down syndrome compared to neurotypical controls measured by [18F]-fluoroethoxybenzovesamicol positron emission tomography imaging. Neurobiology of Aging 148 (2025) 50-60; PMID: 39914061 DOI: 10.1016/j.neurobiolaging.2025.01.008
Russell JK, Conley AC, Boyd BD, Begnoche JP, Schlossberg R, Stranick A, Rosenberg AJ, Acosta LMY, Martin D, Neal Y, Rafii MS, Dumas J, Newhouse PA. Brain Cholinergic Terminal Density and Cognitive Performance in Adults with Down Syndrome Measured Using [18F]-Fluoroethoxybenzovesamicol PET Imaging is Associated with Amyloid Accumulation. Alzheimer’s & Dementia 21.4 (2025): e70134. doi.org/10.1002/alz.70134
Russell JK, Conley AC, Wilson JE, Newhouse PA. Cholinergic system structure and function changes in individuals with Down Syndrome during the development of Alzheimer’s disease. Current Topics in Behavioral Neurosciences 2024 Nov 2. doi: 10.1007/7854_2024_523.
Correlations between age and [18F]-FEOBV uptake in adults with DS and neurotypically developed controls. Shown are the negative beta-values of the whole brain (minus white matter) voxel-based association between age and [18F]-FEOBV uptake in neurotypically developed individuals (A) and adults with DS (B). Yellow indicates a beta value of zero, with colder colors indicating a decrease in [18F]-FEOBV uptake with increasing age. All negative voxels are shown with no masking by significance performed.
