It isn’t noticeable at first, starting with changes to the brain that the brain can compensate for, meaning no real impact on day-to-day functions or cognition.

But as time passes the brain can no longer compensate for these changes and the damage it’s experiencing. Subtle problems with memory and thinking begin to pop up. Subtle turns to noticeable. Noticeable turns to inhibiting the ability to carry out everyday activities and eventually to requiring around-the-clock care.

This is the broad view progression from pre-clinical to severe Alzheimer’s disease, a degenerative brain disease that becomes worse with time and age, and is the most common cause of dementia, as explained by the Alzheimer’s Association.

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In Colorado, an estimated 76,000 people are living with Alzheimer’s dementia, and that number is expected to increase 21% to 92,000 by 2025, a 2020 Alzheimer’s Association report states. As of July 2019, 14.6% of Coloradans or roughly 840,000 people were 65 or older, U.S. Census data show.

But while generally speaking it’s been shown that living in higher altitude communities in places like Colorado can lead to a more active, healthier lifestyle and even prolonged life, how does living at altitude impact and correlate with degenerative brain diseases that cause dementia, like Alzheimer’s?

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In short, the answer is complicated and not well researched by scientists and clinicians, as explained by Dr. Huntington Potter, director of the Alzheimer’s and Cognition Center at the University of Colorado Anschutz Medical Campus.

“As far as I know, there isn’t a lot of evidence one way or another about high altitudes versus low altitudes for Alzheimer’s disease risk,” Potter said. “We can’t say one way or another whether high altitude is a risk factor for Alzheimer’s.”

DEMENTIA AT ALTITUDE

Alzheimer’s disease is namely the result of the accumulation of the protein fragment beta-amyloid outside of neurons in the brain and of an abnormal form of the protein tau inside neurons, as described by the Alzheimer’s Association.

These accumulations over time can contribute to the damage and death of neurons by interfering with neuron-to-neuron communication at synapses, an Alzheimer’s Association report says, and can block the essential transport of nutrients and other essential molecules inside neurons — resulting in early symptoms of memory loss, apathy and depression; later symptoms of impaired communication, disorientation, confusion, poor judgment, behavioral changes; and ultimately difficulty speaking, swallowing and walking as neuron damage gets worse.

At the Alzheimer’s and Cognition Center, which is part of both the CU Anschutz Medical Campus and School of Medicine, clinicians and researchers are dedicated to discovering effective early diagnostics, preventions, treatments and ultimately cures for Alzheimer’s disease and related neurodegenerative disorders, according to its website.

For Potter, that means looking at biomarkers or diagnostic proteins in the blood that can help clinicians predict the disease earlier; conducting projects that look at the longitudinal sort of lifespan of people with Alzheimer’s disease; and other research that can quickly be translated to better care, treatment and hopefully a cure.

Right now, the center is studying a drug called Leukine, which preliminary data shows may actually improve Alzheimer’s disease in the short term, Potter explained. The center also is studying other drugs that attack the disease, which so far are looking very promising as well.

“Leukine may be the first one we found that looks promising but we have several coming up that look promising as well,” Potter said.

“It’s been a tremendous privilege to work with all of the clinicians and scientists and scientist clinicians at the Alzheimer’s and Cognition Center, and we’re absolutely determined to make Colorado one of the places that discovers the cure for Alzheimer’s disease.”

When it comes to looking at the potential correlation between living at high altitude and the risk for Alzheimer’s and other dementia-inducing diseases, Potter and Dr. Peter Pressman of the Alzheimer’s and Cognition Center said it would take great effort, time and funding to research.

Pressman, who is a behavioral neurologist and researcher with the center, said on top of securing and carefully selecting a large group of people living at altitude to participate in a study, researchers would also have to follow that group for around a decade to get meaningful results — which is not impossible, but not easy.

“It’s easy to fund a study for a few years. People give you money to do something for two to three years, but two to three years is not enough time for a process as slow as Alzheimer’s and dementia to really even pick up,” Pressman said. “I’m not saying that’s not possible, it’s doable, but it would take some effort.”

Dr. Brooke Allen, neurologist, founder of Roaring Fork Neurology in Basalt and medical director at Renew Roaring Fork, an assisted living and memory care center in Glenwood Springs, expressed similar thoughts.

Allen said as a part of any mild cognitive impairment or dementia evaluation, her team checks the oxygen level a patient has and considers the altitude at which that person spends most of their time.

Lower oxygen levels can certainly contribute to people experiencing confusion, dizziness and mild short-term memory issues. But outside of looking at oxygen levels and how they could be contributing to symptoms, Allen said she doesn’t consider altitude a higher risk situation.

“I’ve never really personally looked and it … but I think doing a retrospective sort of epidemiology review would probably make sense at first to even see if there’s a need to research it,” Allen said.

At Roaring Fork Neurology, where Allen and her team diagnose and treat headaches, migraines, concussions, Parkinson’s disease, dementia and other disorders of the nervous system, about 25% of the practice is treating patients with some sort of dementia or mild cognitive impairment, Allen said — a percentage that’s stayed fairly stable over the past 10 years she’s been working in the Basalt area.

This mild cognitive impairment means patients haven’t lost the ability to carry out the activities of daily living, but are having some trouble with things like using new equipment, not being able to work a remote control or having more trouble with finance calculations, Allen said.

To treat patients experiencing this mild cognitive impairment, Allen’s team first looks at risk factors like age, gender and DNA, which are not modifiable but are contributors; high blood pressure, diabetes, sleep apnea, high cholesterol, obesity, and exercise levels, which are modifiable; and B12 levels, signs of infection, a potential brain tumor or structural abnormality and oxygen levels, factors which can “reverse” the symptoms being experienced if they exist and are addressed.

But overall, Allen said she feels Roaring Fork Valley residents 65 and older tend to be much younger than their age in terms of their lifestyle, which is a positive in terms of dementia prevention.

About four years ago, Allen and her team conducted a long-term pre-clinical Alzheimer’s trial as part of the Alzheimer’s Prevention Initiative’s Generation Program, a study that looked at the effectiveness of preventative treatments for individuals between 65 and 75 who had no symptoms of dementia.

Allen said over 250 people came in to participate in the study and all generally led healthy, active lifestyles.

“I think in our valley, I’ve experienced meeting those kinds of people and not thinking of altitude as a risk factor but as a lifestyle opportunity in a rural area like ours,” Allen said of the people who participated in the recent study.

Looking at this potential correlation between living at high altitude and risk of Alzheimer’s dementia and others is not just a difficult feat for Colorado researchers — little research with concrete findings exists nationally and globally as well.

One study published in 2015 by Dr. Stephen Thielke in JAMA Psychiatry looked at deaths attributed to Alzheimer’s dementia reported in 58 counties in California to try to determine whether rates of dementia were associated with average altitude of residence. The study found that the counties at higher elevation generally had lower rates of dementia mortality.

“Oxidative abnormalities have been long proposed to be central to the pathogenesis of dementia,” the study research letter states. “One group of researchers previously found that hypoxia prevents neurodegeneration in rats in experimental Alzheimer disease and hypothesized that adaptation to induced hypoxia may prevent dementia. To our knowledge, our work is the first to find epidemiological evidence for such effects. Additional work is needed to determine whether this relationship holds in other populations.”

But beyond this study, there isn’t much conclusive evidence for or against a correlation, as emphasized by Dr. Brent Kious, a psychiatrist, assistant professor and researcher with both University of Utah Health and the school’s Department of Psychiatry.

Kious has studied the link between living at high altitude and major depressive disorder, anxiety and suicide, and said he and his research team have been interested in the impact of altitude on the incidence and median age of onset of Parkinson’s disease, but has not studied this impact or the effects of altitude on dementia risk.

However, Kious said decrements in cognitive performance due to chronic exposure to moderately high elevation might not necessarily translate into an increased risk of dementia, since the symptoms of dementia depend both on baseline cognitive performance and on pathological neurodegenerative processes.

“It is not clear whether altitude would affect those neurodegenerative processes or not, though there is some reason to think that they involve oxidative damage … so relative hypoxia might slow them,” Kious said via email. However, he went on to note that relative and prolonged hypoxia has also been associated with dementia risk, too. “In any case, a good epidemiological study of the association between altitude and dementia should control for things that might be associated with both.”

BETTER UNDERSTANDING AND ACCESS TO CARE

While there may not be good data for or against high altitude as an Alzheimer’s and dementia risk factor, there is evidence that people living in more rural communities do not have the same access to dementia care and treatment as those living in urban areas.

According to the 2020 Snapshot of Rural Health in Colorado, produced by the Colorado Rural Health Center, 721,500 people are living in rural Colorado and 19% of the rural population is age 65 or older. Rural is defined as a non-metropolitan county is no cities over 50,000 residents, the snapshot report says.

In Pitkin County, which is considered rural, 20.3% of the population is 65 or older, according to 2019 census data. And while Chad Federwitz, a gerontologist — specialist in the field of gerontology, or study of aging — and manager of Pitkin County Senior Services, says Alzheimer’s dementia and other dementias aren’t really prevalent locally and that he hasn’t seen any correlation or link between living at high altitude and dementia risk, he does know anecdotally that people may move downvalley, to Grand Junction or the Front Range if they have onset or early dementia because of lack of care resources in the upper Roaring Fork Valley area.

“Given the nature of our rural-ish community, we don’t have the same resources,” Federwitz said, referring to things like long-term assisted living and memory care options, professionals trained in Alzheimer’s disease, dementia and gerontology, and at-home caregiving service providers. “You can go to Grand Junction or the Front Range and have pages and pages of resources, as a opposed to (a handful or so) here.”

Before Federwitz started as the manager of Pitkin County Senior Services, he spent about seven years working in dementia care in the Boulder area, and is an Alzheimer’s Association community educator.

He said he feels education and access to informed and professional dementia and memory care is extremely important for Alzheimer’s and other dementia patients especially because there are still a lot of misconceptions surrounding what Alzheimer’s and dementia are, and unique challenges that come with caring for someone who has a degenerative brain disease.

Allen expressed similar thoughts, noting that a big part of dementia care and treatment is caregiver access and preventing caregiver burnout, especially with more severe states of dementia.

She said she feels a lot of times where people with dementia live in relation to their support system “matters in terms of their outcomes.” And while Allen feels there are an unusually large number of people that live in the Roaring Fork Valley that don’t have family in the valley, many people do tend to have good support networks through friends, which is important if that person is experiencing dementia.

“It really does take a village to help individuals cope with the changes happening in the brain and a lot of times that’s really picked up by a friend,” Allen said. “Oftentimes adult children of these individuals don’t live here, but we try to identify someone to support them, and there certainly are resources in the valley for homecare and private caregivers.”

But while there are some dementia care resources in the Roaring Fork Valley and other more rural Colorado communities, the Alzheimer’s and Cognition Center is working to do more to develop meaningful relationships with health care providers and dementia patients in the state’s mountain communities as part of its mission.

According to Pressman, who is heading this charge on behalf of the CU center, a lot of projects are in the planning stages and process of acquiring funding, but include virtually educating medical providers, nurse practitioners and primary care doctors on Alzheimer’s and general healthy brain aging, and mutual, participatory research with rural Colorado communities and communities of color.

Pressman explained that a lot of research related to Alzheimer’s overwhelmingly is based on middle class, well-educated, white participants. And so while researchers think they know a lot about the disease in general, they really only know about the disease related to this demographic group.

Through the center’s outreach and efforts to better connect with underrepresented communities, Pressman hopes to conduct better science and better serve the larger Colorado community.

“What motivates me is trying to do good work, trying to do good science and to makes sure our results actually represent real life,” Pressman said. “We want to make sure we’re helping everybody, not just a niche group, and that our services are available equitably to as many people as possible.”

Although there’s no clear correlation between living in higher altitude, mountain communities and dementia and Alzheimer’s risk, it is clear that as America’s aging population reaches 65 and older, these medical conditions will remain a relevant risk for seniors.

And with this continued risk and prevalence comes a need for more education, more research, more awareness and more connections surrounding the conditions, according to Federwitz.

“We all agree dementia is a horrible thing that can be overly daunting for everyone connected … but you as a person with a family member who has dementia or as a person with dementia, you’re not alone,” Federwitz said. “In my opinion and experience, there are hidden blessings. Joy can still happen. Happiness can still happen, laughter can still happen, genuine connection can still happen, even if all of those things happen in a moment.”

Editor’s note: This is part 2 of a four-part series on longevity in the High Country. The series is being produced in partnership with The Aspen Times, Vail Daily, Glenwood Springs Post Independent, Summit Daily News and Steamboat Pilot. Read more at aspentimes.com/longevity.