Brain imaging research looks to find Alzheimer's at its earliest stages

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A magnetic resonance imaging (MRI) machine.

Brandeis researchers are embarking on a five-year study to examine activity in a small nucleus in the brain that could identify Alzheimer's disease at earlier stages than ever before.
 
Assistant professor of psychology Anne Berry has been awarded $6.2 million from the National Institutes of Health to examine changes over time in the locus coeruleus, a tiny structure in the brainstem known as the "blue spot" because its high melanin concentrations make it appear dark blue under a microscope. It is the brain's primary producer of norepinephrine, which is essential for memory and supports functions that protect the brain against disease. It is also one of the first brain structures to develop abnormal tau protein, a hallmark of Alzheimer’s disease.
 
Brain imaging technology has advanced significantly over the past seven years to allow for the measurement of small brain structures like the locus coeruleus and the visualization of tau pathology in the living human brain. Berry’s research is in partnership with Massachusetts General Hospital's Athinoula A. Martinos Center for Biomedical Imaging, one of the world's most advanced brain imaging centers.

Anne Berry

"What is clear from these brain scans so far is that normal older adults who don't have memory complaints, who seem to be doing just fine, actually do have measurable tau in their brain in memory regions," Berry said. "For some people, they will maintain these lower levels of pathology. For others, that tau starts to spread out into the rest of the temporal lobe as disease processes accelerate. We think that maintaining healthy levels of the brain chemical norepinephrine is key to determining which path you head down. These early regions are going to be optimal targets for intervention."
 
The study is part of a larger project within Berry’s Neurochemistry and Cognition Lab called the Brandeis Aging Brain Study. Nicknamed ‘BABS,’ the study includes a cohort of healthy, cognitively normal middle-aged and older adults interested in participating in longitudinal research examining the neural basis of age-related changes in cognition. Participants complete neuropsychological testing every few years and are offered other studies conducted by Berry’s lab, including projects focusing on emotional memory and curiosity. The cohort is an inclusive, diverse and representative sample of the greater Boston area, bringing community members into research using state-of-the-art technology and investigating important questions about aging.

As the population rapidly ages, this research comes at a critical time. Alzheimer's disease is a type of dementia that usually becomes apparent with mild memory loss and can eventually lead to an inability to hold a conversation or carry out daily activities. Symptoms typically don't appear before age 60 and the risk increases with age. The Alzheimer's Association projects that the number of people diagnosed with this disease will triple to 14 million people by 2060.
 
About 90 participants in the locus coeruleus study will undergo MRI and PET scans starting this fall at the Martinos Center. They will also provide a blood plasma sample. The participants will return three years later and undergo the same tests again.
 
The images provided by the scans will allow for measurement of tau pathology, the structural integrity of the locus coeruleus and synthesis capacity of norepinephrine and dopamine. The blood plasma sample will measure markers of inflammation, tau pathology, amyloid-beta pathology and offer other potentially useful applications as technology advances.
 
"Putting all of those measures together gives you quite a good snapshot of an individual's brain health," Berry said. "Putting that together with information about changes in cognitive function over time, emotional health, sleep and other lifestyle factors will allow us to comprehensively track older adults’ aging trajectories."
 
The study will also include separate behavioral tests, where 400 to 500 participants will be shown a series of neutral images and emotionally evocative images to test aspects of their memory. Participants ages 60 to 85 are currently being invited to apply for both parts of the study.
 
The NIH's National Institute on Aging awarded the $6.2 million grant in June. Preliminary findings are anticipated as soon as 2025, and the study will conclude by 2027.