March 15, 2022

Imaging technique shows Alzheimer’s impact on brain connections

At a Glance

  • A new imaging technique found that fewer connections between brain cells were associated with the cognitive decline seen in people with early-stage Alzheimer’s disease.
  • More work is needed to see if this type of imaging could be used to diagnose the condition early or measure the effectiveness of new treatments.
Illustration of synapses The loss of synapses, the connections between nerve cells, is thought to cause the symptoms of Alzheimer’s disease.KateStudio / Shutterstock

Alzheimer’s disease is the most common cause of dementia among older adults. The loss of cognitive functioning—the ability to think, learn, remember, and reason—can have devastating effects on patients and their families.

As Alzheimer’s gets worse over time, plaques and tangles of proteins build up in the brain. These are thought to eventually cause the loss of connections between nerve cells, called synapses. Researchers think that this decrease in synaptic density causes the progressive symptoms of the disease.

Until recently, scientists haven’t been able to study synaptic density in the living brain. A compound has been developed for use with positron emission tomography, or PET scanning, that can safely reveal living synapses. This tracer binds to a protein found within synapses called glycoprotein 2A.

Researchers led by Drs. Adam Mecca and Christopher van Dyck from Yale University examined 45 people between the ages of 50 and 85 in a new study of this tracer. The participants had early-stage Alzheimer’s, identified by cognitive testing and imaging of plaque buildup in the brain.

The researchers performed PET scans using the new tracer. All volunteers also underwent extensive tests of brain functioning. These measured performance in five main areas of cognition: verbal memory, language, processing speed, maintaining focus, and the ability to orient objects in space.

The team then compared the associations between test scores and cognitive density as measured by the PET scans. The study was funded in part by NIH’s National Institute on Aging (NIA). Results were published on February 17, 2022, in Alzheimer’s & Dementia.

For all major areas of cognition tested, synaptic density predicted performance. That is, people with reduced synaptic density had lower test scores. This association remained strong after the researchers accounted for overall loss of brain volume, which can occur as Alzheimer’s disease progresses. The association between lower synaptic density and worsening cognition also held after the researchers accounted for the age, sex, and education levels of participants.

For comparison, the researchers tested the ability of gray matter volume to predict cognition. Gray matter is the outer layer of the brain, which normally has a high density of neurons. Reduced gray matter volume predicted poorer test scores in two of the five areas of cognition. This indicates that measuring the loss of synapses can better capture the brain changes that impact cognitive functioning.

“Imaging synaptic density may be a way to detect Alzheimer’s early, before symptoms develop,” Mecca says. “It might also be used to assess experimental prevention and treatment approaches.”

The study only took a snapshot of synaptic density at a single point in time. Longer studies are needed to image people over time as Alzheimer’s dementia develops. Such studies could show whether loss of synaptic density can predict a decline in cognitive health.

—by Sharon Reynolds

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References: Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [(11) C]UCB-J. Mecca AP, O'Dell RS, Sharp ES, Banks ER, Bartlett HH, Zhao W, Lipior S, Diepenbrock NG, Chen MK, Naganawa M, Toyonaga T, Nabulsi NB, Vander Wyk BC, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Alzheimers Dement. 2022 Feb 17. doi: 10.1002/alz.12582. Online ahead of print. PMID: 35174954.

Funding: NIH’s National Institute on Aging (NIA), National Institute of Mental Health (NIMH), and National Center for Advancing Translational Science (NCATS); American Brain Foundation; Dana Foundation; Yale University.