Many have witnessed death and destruction, while others suffered multiple concussions (mild traumatic brain injury) caused by the many explosions to which they were exposed.
While physical scars may not be obvious, behavioral disorders and problems caused by repetitive mild traumatic brain injury (mTBI) are all too apparent in many of these Veterans – the nightmares and sleep disturbance of post-traumatic stress disorder (PTSD), depression, anxiety, memory loss, irritability, impulsivity, persistent headaches and more.
As a laboratory scientist, Peskind can peer into the brain of living Veterans by using sophisticated neuroimaging and, in their group’s mouse blast mTBI model and brain tissue from deceased Veterans, at the microscopic level to see structural damage, neuron activity disruption and other dysfunction that may be the cause of these Veterans’ debilitating symptoms.
For the multi-faceted clinician-scientist, it’s been her way for nearly 40 years to: understand the anguish of her patients; get into the laboratory to pinpoint possible underlying causes; and offer whatever puzzle pieces that she finds so that research teams can develop new targets for prevention and treatment of these disorders.
Peskind is also driven by compassion and commitment to her Veteran patients, who become partners in research, too. “I have so much respect for them,” said Peskind, an SIBCR-supported scientist. “Even after all that they’ve gone through, they remain selfless and devoted to serving the public good.”
Peskind is the Friends of Alzheimer’s Research Professor of Psychiatry in the Department of Psychiatry and Behavioral Sciences at the University of Washington School of Medicine; Co-Director of the VA VISN 20 Northwest Mental Illness Research, Education, and Clinical Center (MIRECC); and Director of both the MIRECC fellowship and a National Institute on Aging T32 institutional training grant.
While her academic title reflects her expertise in Alzheimer’s disease, the other disorders she studies – mild TBI and PTSD, both have been linked to increased risk of Alzheimer’s and other related neurodegenerative diseases. A prolific investigator, Peskind has published more than 350 studies.
Collecting crucial cerebrospinal fluid
One her pioneering studies in 2005 exploded the myth that lumbar punctures, or spinal, taps to draw cerebrospinal fluid (CSF) from research participants are risky, painful and uncomfortable.
Collecting CSF is important for studying fluid biomarkers, which are essential in research into neurodegenerative disease such as Alzheimer’s and Parkinson’s.
Peskind, a hands-on scientist who had performed more than a thousand lumbar punctures in the MIRECC, demonstrated and documented a new and safe method now used by research groups around the world.
Blocking agitation in people with dementia
It was in CSF, that Peskind and co-researchers discovered in 1995 that the brain’s system for storing and releasing the neurotransmitter norepinephrine is enhanced during normal aging and boosts even more in patients with Alzheimer’s disease. This adrenaline hyperactivity, which peaks at 4 p.m., explains the phenomenon of the late afternoon agitation and sometimes aggressive behavior (called “sundowning”), often seen in dementia patients, Peskind surmised.
There are no good treatments for this disruptive agitation for these patients, said Peskind. Atypical antipsychotics are often prescribed, but the benefits are questionable for this group of patients, and they have prominent negative side effects.
Now, with a target to aim – the brain’s adrenaline system – Peskind and longtime colleague Murray Raskind, also a SIBCR-supported investigator and Director of the VA Northwest MIRECC, developed clinical trials to test prazosin, an FDA-approved drug for hypertension, to treat Alzheimer’s disease patients with disruptive agitation that is common in the middle and late stages of the disease. Prazosin works by blocking norepinephrine in the brain – at a receptor called the alpha-1 adrenoreceptor.
Raskind and Peskind had also conducted clinical trials of prazosin to treat trauma nightmares and sleep disturbance in Veterans with PTSD. And both are teaming with Jeff Iliff, an SIBCR-supported neuroscientist, to test if prazosin can improve sleep and the brain’s own waste clearing (glymphatic) system in Veterans with traumatic brain injury.
Trauma from blasts
Today, Peskind turns most of her research attention to mild traumatic brain injury (mTBI), the “signature injury” of the Iraq and Afghanistan wars. It’s estimated that up to 500,000 service members in those wars came home with persistent post-concussive symptoms.
Those Veterans were frequently exposed to blasts, including from improvised explosive devices (IEDs), which send out highly intense shock waves that didn’t necessarily knock them over, but they were apparently harsh enough to rock the brain and cause concussion or mTBI.
In a study published in 2016, Peskind and co-researchers worked with 33 Veterans and found by functional imaging that the more blasts that they were exposed to, the more they showed chronic changes in neuronal activity in the cerebellum. This group of Veterans averaged 20 blast exposures that were severe enough to cause symptoms consistent with mTBI.
To examine these changes more closely, the research team studied the brains of mice that were exposed to mild blasts, and they also found neuron loss in the cerebellum. “It’s the same kind of effect that you see in boxers and other athletes who experience repeated blows to the head and are risk for chronic traumatic encephalopathy (CTE),” said Peskind.
The key in this study was pinpointing the cerebellum, long acknowledged as the center for sensory input and motor output, including movement coordination. Researcher now believe, however, that the cerebellum can influence person’s emotions and cognition.
“Problems with mood, irritability, anger dyscontrol, and impulsivity are very common in Veterans with repetitive mTBI,” said Peskind. “We need to pay more attention to how mTBI affects the cerebellum if we want to fully understand the emotional difficulties that our Veterans with mTBI are experiencing.”
She also noted that 75 percent of the mTBI Veterans she treats also have combat trauma PTSD.
“Something is going on in a very specific part of the brain that we don’t fully understand yet,” said Peskind.
True to form, Peskind’s research points the way for other scientists who may eventually design treatments for suffering Veterans.