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Normal Brain vs. Brain With Dementia

This article is based on reporting that features expert sources including R. Scott Turner, MD, PhD; Darlene Howard, PhD; Peter Lichtenberg, PhD, ABPP

YOU DON'T NEED TO BE A brain specialist to notice certain differences in images of a healthy older person's brain compared to that of someone with dementia. Narrowed, depleted folds on the brain's surface, the presence of blotchy plaques, twisted fibers and significant shrinkage are clearly visible. What you can't see is how brain changes like these affect how people's minds work.

In a program from the National Press Foundation and funded by AARP, "Understanding the Latest on Dementia Issues," journalists heard from a spectrum of dementia experts, including researchers, gerontologists, family caregivers and a brilliant engineer who described her personal journey with early-onset Alzheimer's. In addition, a leading neuroscientist detailed how normal brain aging is very different than changes arising from dementia and not something to be feared.

While some presentations were sobering, others were reassuring – and all highlighted just how complex dementia and brain aging are. Here are a few takeaways:

Dementia Brain Changes

Protein plaques and tangles infiltrate the brain in Alzheimer's. For more than a century, scientists have been staining brain sections with silver to visualize the amyloid plaques and tau tangles that are Alzheimer's hallmarks. Beta-amyloid, a product of protein breakdown, clumps together and disrupts brain cell function. Tau, another protein, forms tangled threads that interfere with communication between brain cells. "A nice, healthy young brain has none of these plaques and tangles," says Dr. R. Scott Turner, director of the memory disorders program and a professor of neurology at Georgetown University. "Whereas, as you get older, they accumulate in the brain." People with normal cognition may have a little amyloid and tau in their brains. However, he says, as you get more and more of these abnormal protein deposits, it causes loss of brain cells (or neurons), brain dysfunction and eventually progressive dementia that leads to death.

Hippocampus involvement affects memory. Alzheimer's typically first affects the hippocampus, a part of the brain that's highly involved in memory formation. That's why, he explains, "the first thing to go with Alzheimer's is making a new memory – old memories are fine." Then, as the disease continues to spread, it "affects more and more of the cortex.". The cortex is the thin, outer layer of the brain.

Inability to make new memories causes many problems. "You forget things, you lose things, you spend more time looking for things," Turner says. "You repeat questions. You have more difficulty doing your job or doing your tasks at home. It takes a lot longer to do things." As the disease progresses, other abilities worsen. "It affects language and visuospatial skills, executive function, reasoning, insight – all the higher cognitive domains."

Alzheimer's disease shrinks the brain. An MRI imaging slide presented by Turner showed a stark contrast in brain size between normal and Alzheimer's brains. “We know that you lose one-third of your brain by the time you come to autopsy," Turner says. "One-third of your brain weight is gone from the atrophy, the neuronal loss, the white-matter loss with Alzheimer’s." A cross-section view of the Alzheimer's brain revealed atrophy – shrinkage – in the areas affecting language, memory and judgment.

Dementia progresses in stages. Everyone experiences mild cognitive changes as they age, Turner notes. With dementia, people show increasing signs of decline over several phases that can last for many years. The preclinical stage is the silent phase during which brain changes occur without measurable symptoms or detectable test results. In this phase, Turner says, the patient knows something's wrong but the doctor doesn't. With mild cognitive impairment, the person and their family are concerned by these changes, and at least one cognitive domain, such as attention, executive function, memory or language, is significantly impaired. However, people can still go about their daily activities. As people pass through moderate to severe phases, dementia increasingly interferes with their everyday abilities.

Of course, many factors contribute to dementia development. Genetics play a major role. Alzheimer's risk rises, in part, depending on whether you have any copies of the ApoE4 gene, and how many. Another gene called TREM2 is being studied for its role in inflammatory action in the brain. Other genetic connections exist.

Recent disappointments in large clinical trials of Alzheimer's drugs have scientists looking at other potential pathways in dementia development. The goal is to find more effective treatments for the disease. Studies should target dementia much earlier in the process by including more participants who have mild cognitive impairment, Turner says. Ideally, long-term prevention trials would recruit normal participants who don't have dementia at all but face a higher risk.

Normal Brain Aging

When it comes to comparing the normal, healthy brains of older and younger adults, younger brains do function differently in some ways – although not necessarily always better.

It's actually a "wonderful" time to be old, says Darlene Howard, a professor emerita at Georgetown University whose research focuses on changes in cognitive and neural systems during aging. The "gray tsunami," with a larger proportion of people ages 65 and older in the population than ever before, is helping drive a host of changes.

Increased political clout and camaraderie, emerging technology like smart homes, better hearing aids, improved cataract surgery, universal access like ramps for everyone from parents pushing strollers to people with walkers and a society that's more accepting of diversity all represent advantages for elders, Howard says.

Fresh perspectives on the aging brain are also emerging. Decades of research from Howard and her peers offer encouragement. Their results counter traditional thinking about what's lost or preserved, what gets worse or improves and what's inevitable versus avoidable as you get older. As for normal brain aging compared to dementia effects, she says, "They're very different beasts."

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