Brain Changes May Occur 30 Years Before Alzheimer’s Symptoms Appear

Alzheimer’s is a devastating disease and typically diagnosed only after symptoms appear, when there’s little that can be done.

But, what if doctors could identify those most at risk — decades before they start losing memories?

Scientists at Johns Hopkins say they’ve identified brain changes linked to Alzheimer’s that can occur decades before the disease’s first symptoms show.

The researchers reviewed medical records of 290 people 40 years and older with a family history of the disease from the National Institutes of Health (NIH) and the Johns Hopkins University School of Medicine in Maryland in an effort to discover predictors of cognitive decline.

“They were all selected based on risk, but none had Alzheimer’s yet, and only some had developed the disease since 1995. This allowed us to look at people over 20 or 30 years before they present clinical symptoms,” Michael Miller, PhD, a study researcher, director of the Center for Imaging Science, and co-director of the Kavli Neuroscience Discovery Institute at Johns Hopkins, told Healthline.

By the end of the study period, 81 participants had mild cognitive impairment or dementia.

Looking back on their records, researchers found significant differences from the study participants who still had healthy mental function.

This included subtle changes in test scores measuring their mental abilities taken up to 15 years before.

When researchers looked at cerebrospinal fluid levels, they said they found a substance linked to Alzheimer’s called tau proteins had significantly increased in a process that started almost 35 years before symptoms developed.

In earlier research by Miller and his team, slight changes were also observed in the brain area responsible for memory almost 10 years before cognitive problems became apparent.

“Our study suggests it may be possible to use brain imaging and spinal fluid analysis to assess risk of Alzheimer’s disease at least 10 years or more before the most common symptoms, such as mild cognitive impairment, occur,” Laurent Younes, PhD, a study author, professor, and chair of the Department of Mathematics and Statistics at Johns Hopkins’ Whiting School of Engineering, said in a statement.

Brain damage by time of diagnosis

Currently, Alzheimer’s disease diagnosis relies mostly on observed mental decline through a series of cognitive tests.

But by this point, Miller said, there’s already severe brain damage.

“The findings were very surprising. Initially we didn’t know if we’d really be able to measure the structural and functional changes that would have been occurring years before symptoms were apparent,” said Miller.

He explained that by the time some of the study participants were diagnosed with cognitive impairment, the changes in brain structure compared to measurements taken years before were striking.

The researchers believe these biomarkers — something that can be measured to indicate the presence of disease — offer one of the most promising paths to early detection.

Early diagnosis is key

When it comes to Alzheimer’s diagnosis and living with the disease, time is of the essence.

“Early diagnosis allows a patient the opportunity to take part in clinical trials, have important discussions with their families around their future, consider financial planning and also understand what’s going to happen, what’s going to change, and actively participate in their care planning,” Heather M. Snyder, PhD, senior director of medical and scientific operations at the Alzheimer’s Association, told Healthline.

She added the earlier diagnosis can even help with drug trials.

“You have to look well before there are clinical symptoms, years before. This has a very strong impact on the design of drug trials and perhaps is why some drug trials may have historically failed,” said Miller. “It may be that if you look too late in the progression of the disease, you’re looking at a very different phenomenon than if you looked earlier when things are still really working in the brain.”

“Maybe some of the drugs that have been shown effective could perhaps be even more effective if researchers looked much earlier in the course of this disease,” he added.

Lifestyle can influence risk

When it comes to Alzheimer’s risk, one of the most prominent factors is family history.

“In terms of what the science tells us, there are hints that we see regarding what may increase an individual’s risk,” said Snyder. “One is first-degree relatives like a parent or a sibling that had Alzheimer’s. This carries a significantly increased risk.”

While little can be done to change your family history, according to Snyder, there are risk factors that you can do something about.

“We’ve seen studies where individuals who are obese or have heart disease have a greater risk,” she said. “Similarly with diabetes, people with diabetes have a significantly increased risk. Also people who aren’t that physically active and people who don’t have what we’d call a ‘brain-healthy’ diet also have an increased risk of cognitive impairment in later life.”

According to the Alzheimer’s Association, eating a healthy and balanced diet lower in fat and higher in fruit and vegetables can help reduce the risk of cognitive decline.

The U.S. POINTER study

Snyder said the Alzheimer’s Association is conducting research to evaluate “if different lifestyle interventions can benefit or prevent cognitive decline in a population of individuals that are at increased risk in later life.”

The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), is a two-year clinical trial evaluating whether lifestyle interventions that target many known risk factors, such as obesity and heart disease, can protect against cognitive decline in older adults.

One factor that has attracted attention is the link between insulin resistance and dementia.

“There have been a handful of studies that have looked at the link between insulin resistance being linked to Alzheimer’s in later life,” she said. “Some research suggests that when sugar metabolism goes awry, that influences the brain’s ability to do certain processes.”

“There are actually quite a few things in clinical trials today that are targeting different aspects of that biology and asking questions about different diabetic medications like metformin and others as potential therapies. Some of that is in clinical trials today,” Snyder added.

The bottom line

New research finds that measurable physical changes that indicate an increased risk of developing Alzheimer’s disease may appear years, if not decades, before symptoms show.

This is important because by the time a person experiences cognitive issues, severe damage has already occurred in the brain.

While we can’t change genetic risk, there are things you can do to reduce the risk such as maintaining a healthy weight, eating a lower-fat diet, and getting enough exercise.