A Stony Brook University medical investigator is embarking on a first-of-its-kind analysis that will allow her to eavesdrop on the human brain, observing it all the way from a healthy state through the complex stages of Alzheimer’s disease.
It’s an endeavor that ultimately will involve more than 100 local volunteers as study subjects, said Dr. Christine DeLorenzo, the lead scientist and director of Stony Brook’s Center for Understanding Biology Using Imaging Technology.
The aim is to zero in on regions of the brain involved in memory, using a type of technology called positron emission tomography, or PET.
DeLorenzo’s efforts mirror a larger research thrust announced by the National Institute on Aging earlier this year: Alzheimer’s disease should be understood by the intricate and dynamic biological forces that are driving it. Symptoms alone are no longer sufficient for diagnosis.
At Stony Brook, DeLorenzo is on the hunt for those biological forces — markers of the disease — as physicians worldwide assert that uncloaking those indicators may ultimately provide ways of spotting the condition years, possibly decades, before overt symptoms emerge.
“We have begun a pilot study of people age 55 and older, looking at the entire range from health to Alzheimer’s disease,” DeLorenzo said.
With an intimate understanding of how the disease attacks the brain, newer treatments can be honed to more specifically target the damage. The hope is to provide interventions in the not-too-distant future that either stop or reverse such abnormalities before they morph into an accumulation of assaults that steal minds and destroy lives.
Alzheimer’s is a relentless neurodegenerative disorder for which there is currently no cure. Doctors still have no clear scientific understanding of how the disorder destroys the cells involved in memory.
The condition is the sixth leading cause of death in the United States, and the only one in the top 10 without a cure or reversible treatment. Currently, more than 400,000 people in New York, including 50,000 on Long Island, are living with the disorder, according to the Alzheimer’s Foundation of America.
Nationwide, more than 5.7 million people are afflicted with Alzheimer’s, the most common form of dementia. The disease is expected to increase explosively as the population ages.
DeLorenzo has focused her research on what’s known as the cholinergic system, made up of cells that are widely distributed throughout the brain. These cells are abundant in the three-pound organ’s hippocampus region, which is associated with short- and long-term memory.
“It’s a very critical system for memory,” DeLorenzo said, noting that Alzheimer’s launches its most aggressive attack on cholinergic neurons — cells that rely on the vital brain chemical known as acetylcholine.
That chemical, a neurotransmitter, is involved in sending signals throughout the brain in a vast communication network that underlies human thought and memory.
Most current treatments target cholinergic cells by blocking an enzyme that breaks down acetylcholine. The problem with the drugs, DeLorenzo said, is their limited effectiveness.
Coping despite the odds
Families affected by Alzheimer’s cope despite the unbeatable odds of a progressive disease and only five drugs approved to treat it over the past 22 years.
In Medford, Susan Miller, who oversees her husband’s life with Alzheimer’s, said the medications improved clarity, but definitely are not a cure.
Her husband, Jay Gassman, was diagnosed in 2012 at age 56 with early-onset Alzheimer’s, a form of the disease that occurs before 65. Early-onset dementia is rare because Alzheimer’s is largely a disease of old age. Regardless of when the disease starts, the medications prescribed are the same.
Gassman, who holds a doctoral degree, had been a clinical psychologist before Alzheimer’s developed. He takes two drugs for the disorder, Miller said.
One is galantamine, which works by helping to slow acetylcholine’s breakdown; he also takes a medication called Namenda, which regulates the activity of a brain chemical called glutamate. That compound is involved in the brain’s ability to process information, store it and then retrieve it. Both drugs are for mild to moderate forms of Alzheimer’s.
“We all would like something better,” Miller said of herself and other caregivers.
“Jay was able to tell me himself at the time that the galantamine was prescribed that it made him feel much clearer, that there was more clarity,” Miller said. “With the addition of Namenda that also seemed to bump things up a bit in terms of clarity and awareness, and he was able to express that.”
Despite the potent medications, Miller is certain of this fact: “He certainly continues to deteriorate. That’s a given.”
“If you didn’t know him, you would not think that anything was wrong,” she said.
“This is the cruelest disease,” Miller said of a condition that is assaulting the brain of her husband, a man who was once an expert on the human mind.
DeLorenzo is buoyed by the possibility that her research may offer something new for patients.
“We believe that we may be able to improve the efficacy of current treatments by gaining a better understanding of the structure and function of cholinergic neurons,” DeLorenzo said.
She and her colleagues will be comparing images of the cholinergic regions in healthy people to those who have Alzheimer’s during the three-year research project.
The Alzheimer’s Foundation of America, based in Manhattan, was so intrigued by DeLorenzo’s investigation that it awarded her a $206,184 grant to conduct the pilot study.
“We look upon this as a possible game-changer, a new ambitious and innovative research initiative,” said Charles J. Fuschillo Jr., president and chief executive of the foundation.
DeLorenzo’s research was funded because it ultimately could help refine methods of choosing the most effective treatments, Fuschillo said.
But while the Stony Brook investigation is generating attention, doctors remain stymied by the paucity of Alzheimer’s drugs.
In the last few years all Alzheimer’s medications in clinical trials have failed, a pattern that has occurred throughout much of the 21st century. Between 2002 and 2012, more than 400 trials were initiated for Alzheimer’s medications, but only one — Namenda — was approved.
DeLorenzo contends that clinical-trial failures stem from a lack of understanding the basic biology of Alzheimer’s disease, something that she and her team are tackling.
“The whole field is moving in the direction that we need to understand what is happening biologically, even before we see symptoms,” she said.