A Veteran's Final Gift

At age 18, Robert “Bob” Hincken enlisted in the United States Marine Corps. His most memorable moment, he shared with his wife, Pat O’Neil, was storming the beaches of Beirut with 1,700 fellow Marines in 1958 amidst a civil war in Lebanon. As noted by historians, the landing was comical in ways as surprised sunbathers scrambled and vendors soon showed up selling sodas and sandwiches. It was also deadly serious, as both Christians and Muslims saw the Marines as uninvited aggressors violating Lebanese sovereignty. It also marked America’s first-ever combat operation in the Middle East.

After Hincken completed his three-year enlistment, achieving the rank of sergeant, he returned home to Philadelphia. He then attended Villanova University before taking a job with the Naval Criminal Investigative Service, better known as NCIS, in Annapolis, Maryland. Eventually, he found himself at the Department of Veterans Affairs in Washington, D.C., where he was appointed assistant inspector general for investigation responsible for, among other things, investigating fraud, waste and abuse at VA hospitals. In 1989, he retired and then took a position at Disabled American Veterans.

 

Hincken finally fully retired in the mid-1990s to Florida and then Bluffton, South Carolina, where the troubles began around 2016. O’Neil described too many lost car keys, among other frustrating episodes of short-term memory loss. Then came disorientation and delusions, including one at an acute behavioral health geriatric hospital where he believed he was back on the job as an investigator for the VA. Gone was the sharp and entertaining extrovert O’Neil fell in love with.

“He was a character as much at home as anywhere else,” laughed O’Neil. “He was strong willed, well-read, well-informed, a funny news fanatic. He had a great sense of people and never met a stranger he didn’t befriend. His other passion was golf – even in his 70s he could shoot his age.”

The end came more quickly for Hincken than many suffering with dementia, said O’Neil. A near psychotic break, fortunately calmed by a greeting of “semper fi” by a hospital security officer who served with the Marines, was the tipping point. A psychiatrist noted symptoms of vascular dementia and recommended a full-time care center.

“It’s such an awful thing to watch – we don’t really know to what extent the person going through it knows he or she is going through it, in the later stages,” said O’Neil.

Months earlier, Hincken and O’Neil had discussed his intention to be an organ donor. Now with his diagnosis of vascular dementia, the organ of choice was clear.

Prior to her husband’s death in October of 2021, O’Neil had reached out to Eric Hamlett, Ph.D., an assistant professor in the Department of Pathology and Laboratory Medicine and the research coordinator of the MUSC Carroll A. Campbell Jr. Neuropathology Laboratory, also referred to as the MUSC Brain Bank, at the Medical University of South Carolina (MUSC) in Charleston. Hamlett found his way there following a graduate school experiment measuring the neural response of songbird babies upon first hearing their mother’s sounds. The findings of this experience amazed him and clarified his career choice. “I was shocked at the level of transformation of cellular biology in these avian brains. From that point on I was fascinated with neuroscience.”

Responding to O’Neil, Hamlett first noted the benefit of her husband preregistering as a brain donor, which offers access to experimental drugs and opportunities to participate in clinical studies aimed at measuring longitudinal changes in patients. He also stressed the importance of arranging to have her husband’s head put on a pillow of ice soon after passing, conceding that “When you lose someone, that’s the last thing you want to deal with.”

 

Hamlett also asked O’Neil for her husband’s medical history, especially records related to his brain health, along with the family’s perspective on his health issues. Hamlett in turn would send her a detailed medical profile, including any initial findings from analyses of Hincken’s brain tissue, which may be genetically informative regarding health risks inherited by his daughters and grandchildren.

“You would be surprised – a lot of families have not had the time to sum everything up,” said Hamlett. “It’s quite therapeutic to do that.”

As the brain bank’s gatekeeper, Hamlett shares donor brain tissue with researchers engaged in studies at MUSC and other centers searching for molecular mechanisms that lead to neurodegenerative diseases. In doing so, Hamlett described a combination of techniques, including proteomics, or the study of proteins, and the activation of designer receptors that he and colleagues found that enhanced memory in a mouse model of Down syndrome (Journal of Neuroscience, Jan. 28, 2015). While advances in health care have significantly extended the lifespans of individuals with Down syndrome, noted Hamlett, they continue to exhibit high comorbidity with Alzheimer’s disease.

“They live so long now, their lifespan has literally tripled since the 1970s, yet no one has come up with a solution to help those individuals,” said Hamlett. “Eighty percent of them develop Alzheimer’s.”

Human brain tissue in such quests is essential, noted Hamlett. While lab-created cell-culture models are informative in picking up specific signaling events that may occur in the brain, he explained, they are doing so in an artificial environment. Consequently, a substantial number of signaling cues that control cell biology are lost in these mechanistic studies.

“One might say I initiate studies of microglia with a cell culture model,” said Hamlett. “It’s very powerful, but a lot of the answers we have from cell cultures don’t necessarily answer what the microglia are doing in the environment of the brain. Are they participating with synapses of neurons, altering fluid in cells or creating bystander effects on the cells around them? There are a lot of these constituents we cannot create without studying real brain tissue.”

 

Hamlett added that cell culture models cannot create connections that are physiologically formed through brain maturation, like language centers. The value of studying brain tissue in general, he said, is the ability to learn about cell biology in different regions that are responsible for different functions of the brain, including memory. Animal studies are helpful in this regard, as mice, for example, have tremendous similarities in their microglial cells, which have the defensive job of supporting the survival of neurons.

“Mice have tremendous genetic diversity relevant to homo sapiens; we’re over 75% identical genetically, but there are huge differences in terms of aging cells,” said Hamlett. “Postmortem human donation is so important because it brings the brain complexity and exact genetic diversity that’s needed to study disease.”

As it turns out, what can be learned from the postmortem human brain works hand in hand with cellular and animal studies, a neural orchestra of sorts, conducted by researchers to get at the pathological consequences of dementia. In a recent study, for example, MUSC researchers found that the brains of people who died of Alzheimer’s disease had 34% fewer pericytes than healthy brains, in the hippocampus, a part of the brain associated with memory. Lining the walls of tiny blood vessels, pericytes regulate the blood-brain barrier and help to remove amyloid-beta, the culprit in Alzheimer’s disease. When pericytes are lost, immune cells and impurities begin to leak into the brain, causing it to become inflamed and eventually leading to cell death and declining mental function. A mouse model of Alzheimer’s showed that pericyte loss in the hippocampus increased levels of a gene called Fli-1 and that blocking this blood protein improved performance on behavioral tests meant to assess memory (Molecular Therapy, 2022).

“We are really excited by these data because they suggest that Fli-1 could be a new therapeutic target for Alzheimer’s disease,” said Hongkuan Fan, Ph.D., an associate professor in the MUSC Department of Pathology and Laboratory Medicine, who led the research team.

Perry Halushka, M.D., Ph.D., Distinguished University Professor of Cell and Molecular Pharmacology, agreed. “Pericytes may play a much more important role in dementia than people originally thought. This is especially true in the aging population, where vascular dementia is going to become a bigger problem.”

That observation, along with the determination of the man she knew, confirmed for O’Neil that her husband’s donation would make a difference.

“Bob’s final contribution to this world we live in, and he made many in his 83 years, was to advance and hopefully cure this horrible disorder,” said O’Neil. “Knowing Hincken, he can do it!”

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Although there are some 20 million living armed forces veterans in the United States, their attitudes toward organ donation have not been deeply examined. In a recent survey of 1,517 New England veterans, however, 96% of them supported donation of organs and tissue, with 59% registered as donors.

Veterans interested in learning more about brain tissue donation can contact the Carroll A. Campbell Jr. Neuropathology Laboratory/MUSC Brain Bank at 843-792-7867 and read more about the Department of Veterans Affairs Biorepository Brain Bank.