The risk for developing devastating Alzheimer’s disease may be detectable in healthy adults younger than expected, and new studies reveal how.
Tests already exist to determine a genetic risk for familial Alzheimer’s disease, which is typically early-onset and less common than sporadic Alzheimer’s disease. Both types cause dementia. However, identifying risk for the sporadic variety of Alzheimer’s — which accounts for about 95% of all Alzheimer’s cases — is not as simple.
A study published in the journal Neurology on Wednesday suggests that the risk factors for sporadic Alzheimer’s can be detected early in adulthood and might make a person more susceptible to cognitive decline.
One of the easiest ways to identify this risk might be to take a close look at images of a patient’s hippocampus, a brain region associated with memory, the study suggests.
Younger adults with various genetic risk factors for Alzheimer’s have a smaller hippocampal volume, said Elizabeth Mormino, a researcher at Massachusetts General Hospital and lead author of the study.
“However, we are not able to determine whether these young subjects with elevated risk actually progress to dementia late in life, since that sort of extended followup is not available,” she added. “Nevertheless, this finding informs our understanding of disease mechanisms by revealing an impact of common risk variants decades before clinical symptoms would be present.”
A surprising link
For the study, researchers used MRI images to analyze the hippocampi of 166 people with dementia and 1,026 people without dementia. The average age was 75. The researchers also determined the polygenic risk of Alzheimer’s disease for each person by probing their DNA for specific gene variants associated with a high risk of developing Alzheimer’s disease. A polygenic risk score is a numeric score based on whether a person has several of those gene variants.
Next, the researchers calculated the same risk score and hippocampus volume in 1,322 healthy adults between the ages of 18 and 35.
The researchers found a small association between a higher risk score and having a smaller hippocampal volume within both older and younger groups. Within young adults, the risk score accounted for about 0.2% of the variance in hippocampal volume.
“I was surprised that we identified a link between our polygenic risk scores and hippocampal volume among young adults, decades before any clinical symptoms of the disease would be present,” Mormino said. “This implies that changes early in life may impact risk of dementia late in life and that these changes have a genetic basis.”
Additionally, the researchers found that among older adults who did not enter the study with dementia, a higher risk score was tied to worse memory function over time and a greater likelihood of being diagnosed with dementia during a subsequent doctor’s visit.
“Alzheimer’s disease starts in the brain many decades before the first symptoms of memory loss appear, but what’s happened over time is that most people don’t realize their risk until they start having memory loss,” said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical Center and NewYork-Presbyterian Hospital, who was not involved in the study.
“Before that, you can have metabolic or functional changes in the brain as well as structural changes. The size of the hippocampus, or memory center of the brain, may start to shrink in the 30s or younger,” he added. “As the science expands, we’ll be better able to understand the true nature of sporadic versus genetic Alzheimer’s.”
Brain scans hold clues
The new findings seem to confirm what was shown in a separate study, published in the journal Biological Psychiatry in March, in which brain scans also revealed structural differences in the hippocampi of young adults with high and low risk scores.
Those researchers analyzed the association between genetic risk scores and brain images of about 300 healthy young adults.
“We had expected to see changes in the hippocampus in relation to risk for Alzheimer’s disease based on the existing anatomical literature but were still somewhat surprised to see them in a relatively young cohort,” said David Linden, professor of translational neuroscience at Cardiff University in Wales and a co-author of the study.
“Similar effects of reduced hippocampal volume in relation to increased polygenic Alzheimer’s disease risk have now been reported for unrelated participants by other research groups,” he added, “which inspires confidence into the robustness of these findings.”
To diagnose Alzheimer’s disease, doctors may perform brain-imaging tests, but those tests are typically to rule out other possible causes for a patient’s symptoms.
Additionally, brain imaging can help doctors identify the disease once there has been damage to a patient’s brain tissue. There still isn’t a way to detect and clinically diagnose Alzheimer’s using brain imaging alone.
How to reduce risk
A majority of adults 60 and older tend to be most concerned about developing Alzheimer’s disease, according to a YouGov survey conducted in the UK last year. Fear of Alzheimer’s even took precedence over cancer and financial concerns in the survey. As the world mourned legendary women’s college basketball coach Pat Summitt, who died at age 64 last week after battling Alzheimer’s, such concerns probably have heightened.
Yet, there’s hope. More research not only could help physicians with using brain imaging and other methods to better identify dementia risk, it might lead to future preventative treatments, Mormino said.
Fear can be paralyzing, Isaacson said.
But “the field of Alzheimer’s risk reduction and disease prevention is exploding,” he added.
“It’s really important that people are not fearful and that younger people don’t think there’s nothing a person can do to reduce their risk and protect their brain,” Isaacson said. “Recent studies finally get us passed the dogma of ‘there’s nothing you can do.’ There are so many things you can do.”
For instance, at-risk young adults can alter their diets to include foods that benefit brain health, as well as focus on getting a healthy amount of exercise and sleep.
“The earlier you detect risk, the better,” Isaacson said. “And the notion that there’s nothing you can do is false.”