Brain changes may occur decades before people experience Alzheimer's symptoms, accumulating evidence suggests.
According to estimates, the prevalence of Alzheimer's disease will double almost every 2 decades.
Detecting Alzheimer's early on makes it easier to plan adequate care and begin therapeutic interventions as early as possible, which may alleviate the symptoms.
Researchers believe that Alzheimer's begins many years before the onset of symptoms. In fact, emerging research has suggested that some Alzheimer's-related brain mechanisms start at least 10 years before diagnosis.
However, it is not yet clear exactly when these changes occur. In a new study, researchers have set out to detect more precise "changepoints" in the evolution of Alzheimer's biomarkers.
Laurent Younes, Ph.D., who is a professor and chair of the Department of Applied Mathematics and Statistics at Johns Hopkins University in Baltimore, MD, is the lead author of the new paper, which appears in the journal Frontiers in Aging Neuroscience.
Studying brain 'changepoints' in Alzheimer's
To find out when the biochemical and anatomic changes occur, Prof. Younes and team reviewed the medical records of 290 people who were at least 40 years old. The scientists accessed the data from the BIOCARD project, which aims to discover predictors of cognitive decline.
The majority of the study participants had at least one first-degree relative with Alzheimer's, which considerably raised their risk of developing this condition.
The researchers had access to the participants' cerebrospinal fluid samples and MRI brain scans, which scientists had collected every 2 years between 1995 and 2013 as part of the BIOCARD study.
During the same period, the BIOCARD scientists carried out five standard tests each year. These examined the participants' memory, learning, reading, and attention.
At the start of the new study, the team deemed all of the participants to be "cognitively normal," but by the end of the study period, 81 participants had developed Alzheimer's disease.
Tau levels change 34 years before symptoms
In the participants that developed Alzheimer's, the Johns Hopkins researchers found signs of cognitive impairment 11–15 years before the onset of any symptoms.
These subtle signs were visible from slight changes in the cognitive test scores, but the participants did not exhibit any symptoms at that point.
Prof. Younes and colleagues also found raised levels of the Tau protein — a biomarker of Alzheimer's disease — in these participants. In fact, they detected higher levels of this protein as early as 34 years before symptom onset.
Furthermore, the levels of a modified version of the tau protein called "p-tau" increased 13 years before visible symptoms of cognitive impairment appeared.
Finally, the team also used computer algorithms to track brain changes in the participants over time. The scientists assigned numbers to different parts of the brain and found that the rate at which the medial temporal lobe changed was slightly different in the Alzheimer's participants.
The medial temporal lobe has an association with memory, and the scientists noticed the changes to this brain region 3–9 years before the participants became symptomatic.
Study co-author and Johns Hopkins biomedical engineering director Michael I. Miller, Ph.D., comments on the findings. He says, "Several biochemical and anatomic measures can be seen changing up to a decade or more before the onset of clinical symptoms."
"The goal," he adds, "is to find the right combination of markers that indicate increased risk for cognitive impairment and to use that tool to guide eventual interventions to help stave it off."
Prof. Younes cautions that brain changes vary considerably between people, the study sample was small, and there are not yet any therapies that we know to work against Alzheimer's at such an early stage.
However, the findings may lead to better diagnostic tests, which could, in turn, inform better treatment choices.
"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."
Prof. Laurent Younes, Ph.D.