Alzheimer’s Inside the Brain

Alzheimer’s Inside the Brain
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For Cynthia Guzman, a 71-year-old living in northern California, profound confusion at a stop sign while driving one day about eight years ago was a clear signal that something was wrong. Now retired, the former nurse says, “I didn’t know where I was going. It was like I woke up at the stop sign,” which was a frightening moment. “I was scared and confused,” Guzman recalls,

She was eventually diagnosed with dementia, and a few years later with Lewy body dementia, a severe form of dementia that can also cause Parkinson’s-like symptoms and hallucinations. She now does a lot of advocacy work for the Alzheimer’s Association, sharing her story so that others might have a better outcome when dealing with dementia.

In all forms of dementia, whether it’s Alzheimer’s disease — which accounts for about 60 to 80% of all cases of dementia — Lewy body dementia or another type of neurodegenerative cognitive illness, the brain undergoes a series of structural and chemical changes. These changes result in the symptoms we identify as dementia, including:

— Impaired memory.

— Impaired language and communication skills.

— A loss of ability to pay attention and focus.

— A loss of good reasoning and judgment skills.

— An increase in feeling confused or disoriented.

— Increased irritability.

— A reduction in visual perception.

— A reduction in the ability to care for oneself and attend to the activities of daily living, such as preparing meals, traveling and keeping appointments.

[See: How Music Helps People With Alzheimer’s Disease.]

“Alzheimer’s is a decline in cognitive and executive function that’s commonly seen in the older population,” says Dr. Vibhor Krishna, a neurosurgeon at The Ohio State University Wexner Medical Center. Though it may be more commonly seen in people in their 70s and 80s, “it affects many people earlier” and may be called early-onset Alzheimer’s or early-onset dementia when it’s identified in younger adults.

What Happens in the Alzheimer’s Brain?

The National Institute on Aging reports that “the healthy human brain contains tens of billions of neurons — specialized cells that process and transmit information via electrical and chemical signals.” These signals allow you to move and think and do all the normal things you do every day. But in a person with Alzheimer’s disease, this signaling process begins to break down.

The AA reports that “dementia is caused by damage to brain cells. This damage interferes with the ability of brain cells to communicate with each other. When brain cells cannot communicate normally, thinking, behavior and feelings can be affected.”

The exact cause of that damage — and why it happens to some people and not others — is still under investigation, but a few specific changes to the brain have been observed in people with Alzheimer’s, including:

Neuronal death and abnormal brain shrinkage. The brain naturally shrinks as we age, but the shrinkage associated with Alzheimer’s disease is caused by the death of specialized cells in the brain called neurons. Neurons transmit nerve impulses and your brain is full of them, but they don’t usually die off as we age the way they do in Alzheimer’s patients. This neuronal death typically begins in the hippocampus, the seahorse-shaped structure deep inside the brain that is critical to learning and memory, the NIA reports. As the disease progresses, neuronal death transpires across other parts of the brain, and may be concentrated in areas that control language, reasoning and social behavior.

Development of beta-amyloid plaques. In the Alzheimer’s brain, amyloid proteins clump up between neurons, and it’s believed that these toxic plaque formations block cellular signaling.

Development of tau protein tangles. Abnormal tau accumulates and forms tangles inside neurons. “In healthy neurons, tau normally binds to and stabilizes microtubules” that deliver nutrients to the cells, the NIA reports. But in Alzheimer’s disease, “abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, which harms the synaptic communication between neurons.”

Changes in the vascular system. If insufficient blood and nutrients are being delivered to the brain, that can also starve the brain of the oxygen, glucose and other compounds it needs for peak performance. Vascular changes may also be implicated in a reduction in the brain’s ability to tidy up after itself, leading to a breakdown of the waste removal system.

Breakdown of the waste removal system. The brain has a highly balanced waste removal system that whisks away cellular wastes that can build up between neurons as they fire their chemical signals. As we age, this process can become less efficient, leading to chronic inflammation in the brain. In the Alzheimer’s brain, this process seems to break down faster than in people who don’t have the disease. “Because it appears that Alzheimer’s is both a cause and consequence of vascular problems in the brain, researchers are seeking interventions to disrupt this complicated and destructive cycle,” the NIA reports.

Understanding Plaques and Tangles

Amyloid protein is “a sticky protein,” Krishna says. It’s produced by the bone marrow and normally aids in fighting infection in the body by surrounding infections, making them easier for the body to fight or remove. But, “there is a mutated form of amyloid in patients with Alzheimer’s, and this amyloid has a tendency to accumulate. And because it’s sticky, it forms these clots,” Krishna explains.

In addition to the amyloid plaques that can gum up the works in the brain, “neurofibrillary tangles made from a protein called tau,” are a second hallmark of Alzheimer’s in the brain. Tau is a “structural protein that’s found within neurons and it allows for transportation of different proteins across from one part of the neuron to the other,” Krishna says. Neurons can have very long appendages called axons, “and those are the parts that turn into nerves and they connect the neurons from one part to the other.” These axons can span “across several millimeters and centimeters, and you need tau protein” to help carry signals along the axons, Krishna explains. But as with the amyloid proteins, sometimes tau can change and begin developing into abnormal neurofibrillary tangles. These tangles disrupt normal cognitive processes.

“It’s been seen that the deposition of amyloid and tau protein in the brain is significantly associated with clinical symptoms (of Alzheimer’s disease), and it’s been hypothesized that the deposition of these plaques and tangles is somehow either a root cause of this problem or a reflection of the underlying pathology in the brain,” Krishna says. In other words, it’s not entirely clear yet whether the plaques and tangles so closely associated with Alzheimer’s disease cause the symptoms directly or are another symptom of an underlying disease process. But in any case, these plaques and tangles are an area of great interest to researchers attempting to unravel how the brain changes as we age and whether there’s a way to prevent or reverse this problem and thereby prevent or reverse Alzheimer’s and other forms of dementia.

[SeeL 14 Ways Caregivers Can Care for Themselves.]

Can Plaques and Tangles Be Cleared?

One theory in the treatment of Alzheimer’s is that if you can slow the accumulation of these structures, you might be able to slow the development of Alzheimer’s disease. Alternatively, if there were a way to break up the plaques and remove the tau protein tangles, you might be able to restore brain function in people who already have a diagnosis. But doing so is anything but easy. That’s in part because the brain has a highly selective and nearly impermeable protection layer called the blood-brain barrier. This barrier, formed by a network of tightly packed blood vessels, prevents many molecules — viruses, bacteria and the chemicals that make up medications — from entering the brain. Intended to act as a guard against potentially dangerous agents, only essential substances, such as glucose, vitamins and minerals essential to brain function, may pass through the barrier to reach the brain. But that makes it very difficult for medications that might be able to clear up some of the unwanted plaques and tangles from the brain to reach their targets.

But Krishna and his team are currently working on finding a solution to this problem, utilizing ultrasound technology delivered via a special helmet to help open the barrier. Opening that barrier could let in medications that can help clear the plaques or possibly stimulate the brain to clear the plaques on its own. “The working hypothesis is that by opening the barrier, you would initiate the process in the brain for clearance of the plaque,” Krishna says.

The study is in Phase 1 right now, and Krishna says the team is looking at whether “you can open the blood-brain barrier safely without side effects,” such as brain swelling or micro-bleeding from the tiny vessels in the barrier. If that’s possible, how reliable is the approach? “These are the questions that we are trying to address,” he says. The hope is that the ultrasound technique will improve the efficacy of treatment for Alzheimer’s, but Krishna says it’s too early to make any predictions about whether this ultrasound therapy may be coming to a clinic near you anytime soon.

In addition, the research is expected to provide more information about Alzheimer’s disease itself, “so that’s the major excitement that we have.” Developing a tool that “gives us access to the brain in a very precise way that we didn’t have before,” could lead to new breakthroughs in the treatment of a terrible disease that affects some 5.8 million Americans.

[See: 9 Habits That May Reduce Your Risk for Developing Alzheimer’s.]

What Can I Do Now to Slow or Prevent Alzheimer’s?

In the meanwhile, there are a few things you can do to improve your situation if you or a loved one is dealing with Alzheimer’s.

Get diagnosed. Remember Cynthia Guzman from earlier? Her son, Ed Ortiz, says that getting diagnosed as early as possible is something he wishes everyone knew was really important. “If family members are noticing something, or see that someone is experiencing memory or behavior challenges, say something. Have that conversation, because early detection and early diagnosis has a lot of benefit.” Medications do exist and getting the right support from the medical community as well as family and friends can make a big difference. “The sooner you can get on medications and the sooner you can get access to more services and support, the better off you’ll be in the long term.” In fact, his mother is still living independently, despite her disease, in part because she got good help early on.

Eat right. A diet that lowers overall inflammation in the body might reduce the severity of symptoms of Alzheimer’s. Many people also swear by the power of curcumin, a molecule found in the bright orange spice turmeric that’s used widely in Indian cuisine, for reducing inflammation, particularly in the brain. Some people try supplements to help with getting nutrients that may be supportive of brain health, but it’s important to talk to your doctor about anything you’re taking, even if it’s labeled as an herbal supplement or sold over the counter.

Exercise. Physical activity stimulates the brain as well as the body, and it’s believed that exercise can boost the levels of certain chemicals in the brain that are beneficial to memory and learning. So move more — a brisk walk, some gardening, dancing or yoga. Most any kind of movement will confer some benefits.

Sleep. While we sleep, our brains are hard at work clearing the waste that has accumulated during the day, and it’s believed that people who are chronically sleep deprived may be at higher risk of developing Alzheimer’s and other forms of dementia.

Socialize. Social interaction is thought to be an important means of combating Alzheimer’s disease and dementia. Socialization helps with the feelings of isolation and depression that often accompany a dementia diagnosis, and it may actually help slow down the progression of the disease and reduce the rate of memory loss.

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