MEMORY
Protection
A researcher wants to make surgery safer for aging patients’ brains.
A
B Y A M A N D A M . G R O S V E N O R l ILLUSTRATION BY VINALD FRANCIS
S A CLINICIAN, LORI DAIELLO, PharmD, ScM,
worked with countless families struggling to care for
loved ones with dementia and Alzheimer’s disease. She
says she’d hear things like, “‘Mom’s memory was fine
until after she had that knee replacement, or that shoulder surgery.’”
The frequency of the complaints “really concerned me,” Daiello
adds. “So I thought, well, maybe I’ll do research.”
Previous studies found that up to 45 percent of senior patients
experience postoperative delirium (POD): temporary confusion,
disorientation, and memory or attention problems during the week
following surgery. Postoperative cognitive dysfunction (POCD),
meanwhile, affects 5 to 55 percent of patients and may not be
apparent until several months after they leave the hospital.
Although most patients with POCD will return to normal within
six months of surgery, studies also showed that up to 15 percent will
experience “a more serious condition that can lead to persistent
problems with memory or thinking,” says Daiello, a researcher at
the Rhode Island Hospital Alzheimer’s Disease and Memory
Disorders Center.
“The majority of people will have good and safe outcomes
following surgery,” she adds. “But the older we get, the risk of
developing some type of postoperative cognitive disorder increases.”
Daiello first tried to get to the bottom of this as a research fellow
and then an epidemiology graduate student at Brown in the late
2000s, when the prevailing literature claimed that anesthesia was
the reason some patients’ cognitive abilities declined after surgery.
But more recent research indicates it’s probably not the primary
cause. “So if it isn’t anesthesia, what is it?” she wondered.
HOLE IN THE WALL
The answer may lie in the blood-brain barrier, “one of the most
fascinating parts of the brain that most people have never heard
of,” Daiello says.
The barrier is formed by the endothelial cells that line the tiny
blood vessels surrounding the brain, which join very tightly in a
nearly impenetrable junction. This “wall” is supposed to keep the
brain safe by preventing noxious substances in the blood from
entering its environment.
However, for reasons that are unclear, the blood vessels that form
this protective structure can become damaged over time, letting in
potentially harmful substances. Daiello says that in some people, the
combination of a “leaky” blood-brain barrier and high concentra-
tions of certain inflammatory proteins found in the bloodstream
after surgery may be at least partly responsible for postoperative
cognitive problems, by harming neurons in the aging brain.
Recent research shows that the blood-brain barrier is also leaky in
some neurodegenerative diseases like Alzheimer’s, ALS, epilepsy,
and multiple sclerosis, as well as in traumatic brain injuries and
strokes, she adds.
Now Daiello, an associate professor of neurology and of health
services, policy, and practice (research) at Brown, can test the
hypothesis, thanks to a five-year, $3.8 million grant from the
National Institutes of Health.
Over the next five years, her research team will scan the brains of
200 people undertaking major surgery, both before and then three
months after their operations. The researchers will also conduct
paper-and-pencil memory tests and study inflammatory factors in
blood to identify certain proteins that might provide clues to what’s
going on biologically.
Anesthesia isn’t “entirely off the hook” as a possible contributor to
memory loss, Daiello says. But she hopes that studying the blood-
brain barrier might help scientists find ways to prevent postopera-
tive cognitive problems in senior surgical patients.
“More older people facing major operations are questioning
whether surgery intended to heal the body might harm the brain,”
she says. Identifying and understanding the mechanisms behind
cognitive impairment is an important first step toward finding
“effective ways to protect the aging brain.” ●
HEALTH DISCOVERIES l WINTER 2020 17