There are no cures for Alzheimer's disease, but researchers have made some promising breakthroughs -- like the development of aducanumab, the first new treatment for the disease since 2003.
In today's installment of our look at the disease, we'll dive into treatments, their limits and challenges surrounding them.
Alzheimer's is a brain disease that occurs when certain brain cells (neurons) receive damage (and cause changes in the brain). Changes include the accumulation of two abnormal proteins -- beta-amyloid and phosphorylated tau.
In Alzheimer's, the beta-amyloid proteins clump together, forming plaques. The clumps may block cell-to-cell signaling at synapses. They may also activate immune system cells (microglia) that trigger inflammation and devour disabled cells. Tau (proteins) may accumulate and form threads and tangles inside neurons. Tangles block neurons' transport system, harming communication between neurons.
As Alzheimer's disease progresses, plaques and tangles tend to spread through the brain cortex in a predictable pattern, according to www.alz.org. The rate and progression varies greatly. Toxic beta-amyloid and tau proteins continue to trigger immune system cells.
Chronic inflammation may set in. Atrophy (brain shrinkage) occurs because of cell loss.
Diagnosis
Close family members notice the first signs of dementia, said Harathi Bandaru, a neurologist at Capital Region Medical Center.
"Usually, you get to know about it when family and caregivers notice they are unable to take care of their things," Bandaru said. "They forget. Memory is the main thing."
In its report, "2022 Alzheimer's Disease Facts and Figures," the Alzheimer's Association points out that primary care physicians were responsible for 85 percent of initial diagnoses for people with dementia. The remaining 15 percent of patients received their diagnoses from specialists, such as neurologists, psychiatrists or geriatricians (primary care physicians who have received additional training in treating older adults, especially those 65 and older, according to WebMD).
Despite the "vast majority" of diagnoses made by those primary care physicians, of said physicians, about 40 percent said they were never comfortable personally making the diagnoses of Alzheimer's or other dementias.
A patient's primary care physician generally refers them to a neurologist, Bandaru said.
Neurologists will do all their dementia work-ups, she said.
"You have to make sure of the basic things first," Bandaru said. "You want to make sure they don't have vitamin deficiencies, especially B-12, causing that memory problem. First things first. Easy things first.
Some studies have shown that B-12 deficiency can lead to Alzheimer's-like symptoms, such as memory loss and atrophy, according to www.mayoclinic.org.
Physicians also want to make certain patients are not depressed, Bandaru said. Sometimes, depression itself can cause dementia.
"That is called a pseudo-dementia. It's not real dementia, but because you're depressed, that's why you are forgetting things," she said. "You are not paying attention."
It is important for a physician to do the first things first, she reiterated.
They've ruled out depression and vitamin deficiency. Then, maybe it's real dementia.
"Then, you talk about ... usually if you see a patient less than 65 years old, then it's kind of early onset," Bandaru said. "Then, you can be very aggressive, getting a CT (computerized tomography) scan, you're looking for amyloid plaques."
Care and treatment
The treatment is the same, she said.
The first line of treatment, is the cholinesterase inhibitors. Cholinesterase inhibitors are used to increase communication between the nerve cells to try to improve the symptoms of Alzheimer's, according to www.drugs.com. (They stop enzymes from breaking down a chemical (acetylcholine) neurons use to communicate with each other).
To help maintain memory, physicians prescribe donezepil, for which the most common side effects are nausea, diarrhea and headaches; galantramine, for which common side effects include chest pain, dizziness, irregular heartbeat and unusual fatigue; and rivastigmine, which may cause loss of appetite, diarrhea, weakness and tremors.
As cases advance, physicians may prescribe memantine (brand name Namenda). Memantine decreases abnormal activity in the brain. It may slow the loss of thinking or remembering abilities.
"When you have a lot of glutamate in your brain," Bandaru said, "your brain capacity -- everything goes down. (Memantine) keeps it under control."
Glutamate is naturally occurring in the brain, and has the effect of exciting nerve cells. However, it may excite nerve cells to a point in which they die, according to the National Library of Medicine.
"Usually, when there is mild to moderate Alzheimer's dementia, you try this," she said. "When they have moderate to severe (dementia), then you do it in combination with (the other) medications."
Physicians offer individualized treatments for all patients, said Lenora Adams, an internist and the vice president of medical affairs for SSM Health St. Mary's Hospital. In each case, physicians seek to insure benefits outweigh the risks.
A new hope
Alzheimer's medications have been the same for many years (since about 2003).
Then, in June last year, the U.S. Food and Drug Administration (FDA) announced it was giving accelerated approval to Biogen's new product aducanumab (brand name Aduhelm).
"It was so fascinating. It gave a lot of hope," Bandaru said.
The FDA's accelerated approval may be used for drugs intended to help patients overcome serious, or life-threatening illnesses when they provide a "meaningful therapeutic advantage" over existing treatments.
Alzheimer's is an irreversible, progressive brain disorder that destroys member and thinking skills, eventually resulting in patients being unable to conduct even the simplest tasks, the FDA pointed out.
Aducanumab is a monoclonal antibody -- laboratory-produced molecules that can mimic the immune system's attack on cells. Certain monoclonal antibody treatments were found to be helpful in preventing the virus that causes COVID-19 from attacking human cells.
The FDA conducted three studies of aducanumab, using 3,482 patients. Double-blind, randomized, placebo-controlled studies of Alzheimer's patients showed a "significant dose- and time-dependent reduction" of plaques for those patients who received the drug. Patients who received placebos did not have plaque reductions.
However, soon after the U.S. Food and Drug Administration granted accelerated approval of aducanumab in June for treatment of Alzheimer's, the Centers for Medicare and Medicaid Services (CMS) raised concerns about the drug. It announced early this month that it would put significant limits on how it would cover the drug. The agency said it would only cover the drug if it were for patients who are involved in studies of its effectiveness.
"We really need more evidence and studies around the drug to prove that it benefits patients," Adams said.
Alzheimer's Association was deeply disappointed by the CMS decision, said Breana Tucker, senior program director.
"We're very concerned with this decision," Tucker said. "We are going to continue to work with health care systems, providers and communities nationwide to assure access to quality care."
Aducanumab targets amyloid proteins. However, some Alzheimer's experts argue that the company who makes Aduhelm, Biogen, has not proven that the drug does what it claims.
And it announced exorbitant prices -- at costs of more than $56,000 per year, according to the New York Times. The newspaper reported that Biogen reduced the price by about half after physicians refused to prescribe it, and it experienced poor sales.
Because it seems to affect amyloid deposits, there was widespread hope that aducanumab really helps, Bandaru said.
"It is showing good reduction -- a substantial reduction of amyloid plates -- but there is no substantial evidence to show that it is stopping the progression of the disease," Bandaru said.
Despite the setback, the Alzheimer's Association continues to fund research.
With $300 million active in 920 different projects spanning 45 different countries, it is the largest nonprofit funder of Alzheimer's research in the world, Tucker said.
"This was the first (treatment) to address the underlying biology of Alzheimer's," Tucker said. "It won't be the last. We still are excited and see different ... other drugs in the pipeline that are in research now.
"We are looking at all different targets for Alzheimer's research. We are leaving no stone unturned. We are looking at innovative approaches that may lead to new therapies."
A limited population
Even had the CMS chosen to pay for treatments, the population aducanumab may treat is limited.
"I don't think it's going to be used frequently, and it's such a narrow classification of patients," Adams said. "It has to be monitored so closely, so (patients) don't show adverse affects."
Patients must be in early stages of the disease (and have only mild dementia) to receive the treatment. They must have stable psychiatric conditions and have no cardiovascular problems.
And potential patients may not possess the APOE4 gene, which may increase the risk for dementia. Studies suggest presence of the gene may indicate brain cells struggle to process fats.
"So, there are a lot of limitations," Bandaru said.
Additionally, before the patient begins the aducanumab therapy, the patient must receive a baseline MRI scan for a baseline look at the brain, so physicians may identify changes within the brain during treatment.
After the patient receives a fourth dose, they must receive another scan to make certain there is no bleeding in the brain. (The second dose comes four weeks after the first. Then, the third and fourth doses are each given after eight weeks.)
At St. Mary's Hospital, as with other emerging treatments, if patients truly understand the risks versus the benefits of the drug, physicians would be willing to find the nearest place a patient might be included in a clinical trial of aducanumab, Adams said.
It has done so with cancer therapies -- chemotherapeutic treatments.
"I would caution every individual patient to be fully informed of the risks and benefits of any given treatment," she said.
"Write your questions down for your doctor, so you're 0ranganized. Make sure you get all your questions answered.
"This is one of those cases, if they want to get involved in a clinical trial and work with a team that is investigating a drug to work with ... work with someone who has the most experience using it."
Physicians
The Alzheimer's Association report showed the need for dementia care is increasing, far outpacing the number of caregivers available.
In its survey of physicians, it found that 50 percent of (primary care physicians) said they were not adequately prepared to care for those patients.
"More than 25 percent reported being only sometimes or never comfortable answering patient questions about Alzheimer's or other dementia," the Alzheimer's report stated. "Given this discomfort and uncertainty, almost one-third of PCPs refer patients to a dementia specialist."
The report followed up, stating that most primary care physicians (55 percent) added there are not enough specialists in their areas to meet patient demand.
The National Center for Health Workforce Analysis said, the report shows, there was a shortage of geriatricians in 2013. However, the shortage is growing rapidly as the population facing dementia ages. The analysis projects the number of geriatricians needed by 2050.
Its estimates show the United States will have to triple the number of geriatricians practicing in 2021 to meet just 10 percent of demand in 2050 (going from 5,170 of the specialists to 15,417). Missouri will also have to triple the number practicing in 2021 to meet 10 percent of demand in 2050 (going from 91 to 283).
"These shortages will affect states differently," the report highlights. "For example, Hawaii and Washington, D.C., have more than enough or almost enough geriatricians to meet the approximately 10 percent of those age 65+ projected to have Alzheimer's dementia in 2050. In contrast, 12 states need to at least quintuple the number of practicing geriatricians by 2050 to care for (10 percent of) those 65 and older projected to have Alzheimer's dementia."
The urban/rural divide adds to the challenges. Forty-four percent of urban primary care physicians, and 54 percent in suburban areas reported shortages of specialists in their areas, while 63 percent in small cities or towns and 71 percent in rural communities reported lacking specialists.
The shortage of specialists is a barrier to timely diagnoses. And, lack of diagnoses means delays in treatments, care and support, the report states.
"During this lost time, people living with dementia could be enrolled in potentially life-changing clinical trials of new treatments, receive emotional support by joining a support group of others living with Alzheimer's or hire an eldercare attorney or other professional to begin planning for caregiving, housing and income changes as Alzheimer's progresses," the report states.
Other caregivers
Workers aren't prepared for their aging patients.
The Alzheimer's Association points out that nurse practitioners, registered nurses, social workers, pharmacists, physician assistants and case workers each may receive special training for treating older adults.
But, few do.
In 2021, with 325,000 nurse practitioners in service in the United States, only 12 percent had expertise in gerontological care. Less than 1 percent of registered nurses, physician assistants and pharmacists specialized in geriatrics.
"Although 73 percent of social workers serve clients ages 55 and older, only 4 percent have formal certification in geriatric social work," the report said.
Other health area professionals who may provide their services at home or in skilled nursing facilities offer physical therapy, occupational therapy, wound care, intravenous injections and catheter care.
Collaborations between skilled care and primary care providers can improve care while reducing cost, the report says.
One model that relies on a team composed of a primary care physician, registered nurse, social worker, medical assistant and technician who could administer neuropsychological tests showed savings of as much as $2,856 per patient annually, the report said.
Another dementia care program co-managed by nurse practitioners and physicians showed promise, the report stated. It resulted in fewer individuals being placed in nursing homes, compared to those who received standard care.
Results indicate that investing in a wide range of professionals and mobilizing them in collaborative care models saves money and improves care, the report found.
Prevention
Exercise is the best preventive measure someone may take for Alzheimer's disease, Bandaru said.
Solve puzzles, play memory games, compete in cards with friends and family, she said.
"You have to make your brain think and learn new things. When you learn new things -- even though you're aging -- (it helps)," she said. "You have to be a lifelong student. You unfold many great, miraculous things in your brain, then there are less chances of dementia."
The exercise can be a simple as dancing -- learning new steps. A person's brain meets the challenges and opens up to learning new things, she continued.
"I'm not going to say they don't get dementia at all, but you are increasing your chances with better lifestyles," Bandaru said.
"Walnuts, almonds, flax seeds, sesame seeds -- it helps depression. It helps fatigue," she said. "Avoid sugary foods. You're killing your brain if you eat too much sugary foods. Any processed foods, any preservatives, they are dangerous. They cause more amyloid accumulations."
Control risk factors, such as hypertension, diabetes and high cholesterol, she said. Those conditions make someone more prone to Alzheimer's disease.
Sometimes, give rest to your brain. Take up yoga.
"Basically," she said, "exercise, lead a healthy lifestyle. No smoking."
Editor’s note: This is part two of an occasional series on Alzheimer’s disease.
See also:
Diagnosing issues behind memory loss can be challenging
Previous coverage includes:
Alzhemer’s disease afflicts 6.5 million Americans: https://bit.ly/3MrQj96
Losing a loved one to dementia is slow, painful: https://bit.ly/3k7Gots