Dr. Cynthia Carlsson from the WI Alzheimer’s Disease Research
Center, is looking at the impact of
fish oil on the effects of Alzheimer’
s disease on veterans.
devoted her life’s work to researching the disease and finding effective treatments and eventually cures. She came to Madison in 1995 to do a
residency in trauma and medicine and is now a part of the Wisconsin Alzheimer’s Disease Research Center.

“We really try to cover the whole breadth of dementia care, making sure that we get good science so that we can develop prevention therapies
and treatment,” Calsson said in her office at the Middleton VA Hospital. “We also support caregivers and patients who already have the
disease. We also promote awareness so that people realize what is normal aging versus what is a worrisome issue that they should see their
physician for.”

The WI ALRC has chosen to develop longstanding relationships with the African American and other communities of color in Madison to
ensure that their research — and treatment — are effective for all segments of the population.

“We want it to be a nice continuum where we are learning from our research and giving right back to the community and the community is
giving us good ideas for the research,” Carlsson said. “Grassroots connections are very important. Otherwise, we don’t understand what the
key changes are in people who are in diverse communities.”

Carlsson is currently involved in the BRAVE study at the VA, which stands for Brain Amyloid and Vascular Effects Study, which is looking
into the impact that fish oil may have on the progression of Alzheimer’s disease.

Veterans are at increased risk of Alzheimer’s disease and African Americans and Latinos serve in the Armed Services at a higher rate than their
percent of the U.S. Population.

Why does it impact veterans at a higher rate?

“A lot of veterans have a lot of vascular risk factors,” Carlsson said. “They have a lot of depression and other factors that have affected their
lives like PTSD. Those factors influence what kinds of things that they are at risk for and what kind of brain changes they are at risk for. We
try to work with these different communities to help us understand what the key factors are that are affecting them personally and then
integrate that into our research. The trauma of battle does affect people physically and mentally. We know that veterans who have been in the
service tend to have more post-traumatic distress disorder, depression and anxiety. We’re not exactly sure how those factors tend to have a
negative impact on brain health. By including those and studying those as we look at ways to prevent the disease, we’re hoping to see we
could help people get the treatment they need earlier for depression, PTSD and other factors that may alter their risk for dementia. There are a
lot of factors within the service that can affect veterans’ health. It could be just the thought of being there and the mental struggles that people
go through such as the fear of being injured. There are types of trauma that occur in the service that women especially are at risk for, military
sexual trauma and others. There are a lot of different types of trauma besides the direct combat trauma.”

The buildup of amyloids in the brain is similar to the buildup of plaque in the blood vessels: they inhibit bodily functions.

“We can get buildup of clustural plaques in the arteries that help block the blood flow,” Carlsson said. “We can also have a buildup of a protein
called amyloid in the plaques in the brain tissue itself. There are a couple of different plaques that can negatively affect our brain health. In the
study, we are actually looking at both of those kinds, the blood vessel build-up of plaques and also the brain tissue that amyloids cluster in.”

During the past few decades, fish oil has gained prominence in its impact on heart health, spurred by the documented long lives of Japanese
fishermen. Carlsson and WI ADRC want to see if fish oil can have an impact of Alzheimer’s disease in veterans.

“There are some beneficial effects that fish oil has,” Carlsson said. “Somehow, it tends to improve blood vessel function. It helps to reduce
inflammation. There are a lot of beneficial effects of fish oil. Sometimes people think it may be that you need to have it in the diet itself and
actually eat the fish. A lot of these diet studies show that eating something in its natural state is probably more effective than a pill. But then to
find enough of that in its natural state, you would probably have to eat a lot of fish or a lot of fruit and vegetables, which we don’t encourage
people to do. But in our VA study, we are using a high dose prescription fish oil, more than you would be able to eat in your diet to see if that
higher dose has an even greater effect.”

The thought is that since heart health and brain health are often intertwined, then perhaps fish oil will also be helpful in the battle against
Alzheimer’s.

“Not only does fish oil help the blood vessels to the heart, but also the blood vessels to the brain to help make sure that the amyloid is cleared
well and gives good blood flow to nourish the brain as well,” Carlsson said. “For this study, the BRAVE study, it’s brain amyloid vascular
effects. It’s in veterans who are 50 to 75-years-old. People who have apparent Alzheimer’s, people who have a general vascular risk profile,
we’re trying to see if this prescription can help improve the blood flow to the brain, reduce the amyloid buildup and help improve and maintain
good cognitive function. It’s an 18-month study. We’re aiming for 150 people. We have about 50 people so far. And so people will be
prescribed either the prescription fish oil or a matching mineral oil placebo.”

Now when the term placebo is used in association with medical research, some people shudder when recalling what happened with the
Tuskegee study on syphilis resulted in the African American male subjects going untreated. Carlsson’s and the WI ADRC’s research makes
sure that there is no harm no matter what phase of the research African Americans and others are involved in.

“With all clinical trials, we have to have both a treatment and a placebo,” Carlsson said. “Unfortunately some studies have found that placebo
therapies are safer than the drugs themselves. That’s why we always need a comparison group of people taking the placebo medicine, not as a
way to not be helpful to both groups, but we really have to see because sometimes, something will change over time. If I just looked at people’
s amyloid levels in their brains at baseline, get everyone treatment and then look at everyone at the end, then it may be that just over time, the
levels just naturally go down. We wouldn’t be able to tell if it’s the medicine or just the natural time course of what happens. Without that
other information, you might prescribe a whole bunch of people to take this medicine, pay for the cost, suffer potential side effects and it
might not have any benefit to them. That placebo arm is just as important as the treatment arm to see if medicines are helpful or not.”

And speaking of being helpful, if African Americans want the results of the research to be relevant to the African American community, then it
is important that African Americans and Latinos participate in all phases of the study.

“Having a well-represented population is really important to our program so that we can make sure that the results that we find are applicable
to all people,” Carlsson emphasized. “If we only look in a certain subpopulation of veterans, such as only non-Hispanic white adults, then our
results are only generizable to non-Hispanic white adults. We want to make sure that we have good representation of women and men and
people from different racial and ethnic backgrounds. Those are the factors that are going to help us best to understand who benefits most as
Researching the Impact Fish Oil on Alzheimer’s Disease
and Veterans
The Sacrifice May Not End with Military
Service
By Jonathan Gramling

With the continued growth of the number of Americans over the age of 65 —
up 1.4 million since 2014 to today’s 47.8 million — the incidence of Alzheimer’
s disease is also on the rise. Alzheimer’s, which can devastate a family’s
financial and emotional resources, has had an especially devastating impact on
the African American and Latino communities with African Americans twice as
likely and Latinos 1.5 times as likely to contract the disease.

Dr. Cynthia Carlsson has been concerned about Alzheimer’s disease since high
school when her grandmother was diagnosed with Alzheimer’s and has
we move towards personalized medicine. We can figure out, ‘This
community tends to benefit more. Or this community tends to have more
blood pressure problems or factors that are more important to their risk of
dementia.’ We can help tailor our treatments and our therapies towards
those different communities and individuals.”

Participation in the study lasts 18 months where in addition to taking the
fish oil prescription, participants come into the clinic three times for tests.

“The veteran would have a baseline Lumbar puncture procedure,”
Carlsson said. “We put a thin needle into the lower back area and collect
some spinal fluid. They take some cognitive tests and also an MRI scan.
They have that done at three different points in time. From that
information, we can tell if the medicine is helping their thinking and some
of these markers that we are looking for. I have personally done over
1,000 Lumbar procedures. We’ve done thousands in our program. Most
people tolerate it very well. Most people are nervous about it, but tolerate it
well. It has a little discomfort with a pressure sensation. Usually if
someone gets a side effect, they get a headache that can come after the
procedure. But the risk is less than two percent in our program. It’s a
pretty low chance of having a side effect afterwards. But people can have
a side effect and we walk them through how to manage that if they do get
headaches or low back discomfort.”

And what is the reward? It’s gaining more knowledge about your own
health and assisting future African American and Latino veterans enjoy
their retirement, limiting the level of suffering they experience after they
have served their country.