Alzheimer's risk may be detectable from age 18 with genetic scoring

Researchers have developed a genetic risk score that they say could pinpoint which adults are at risk of developing Alzheimer's disease decades before symptoms arise.
Elizabeth C. Mormino, Ph.D., of Massachusetts General Hospital in Charlestown, and colleagues reveal how they used the score to identify possible indicators of Alzheimer's disease (AD) in healthy adults as young as 18.


The researchers recently published their findings in the journal Neurology.

AD is one of the most devastating and challenging diseases of our time, affecting more than 5 million adults in the United States, with this number expected to triple over the next 30 years.

The study authors note that the pathophysiologic processes of AD are believed to occur for at least a decade before symptoms of the condition appear.
"Given that current clinical trials are testing whether therapies can slow memory and thinking decline among people at risk for the disease, it is critical to understand the influence of risk factors before symptoms are present," says Mormino.

While the exact causes of AD remain unclear, it is thought that genetics play a role. For example, studies have shown that people who possess a form of the APOE gene - known as APOE e4 - are at increased risk of the disease.

"In addition to the APOE gene, to date 21 common genetic variants have been associated with AD in large genome-wide association study meta-analyses," say the authors.

Higher genetic risk score linked to worse memory, smaller hippocampus
For their study, the researchers created a so-called polygenic risk score.

They did so by analyzing the genomes of 166 adults with dementia and 1,026 adults without dementia. They developed scores based on whether the adults - who were an average age of 75 - possessed a number of genetic variants associated with increased risk of AD.

Fast facts about Alzheimer's
Every 66 seconds, someone in the U.S. develops AD
AD is the sixth leading cause of death in the U.S.
This year, AD will cost the U.S. around $236 billion.
Learn more about Alzheimer's
The researchers also analyzed the participants for a number of markers of AD, including decline in thinking and memory, volume of the hippocampus - the brain region associated with memory - and clinical progression of AD.

Additionally, the researchers applied the polygenic risk score to 1,322 healthy adults aged 18-35 and assessed the volume of their hippocampus, in order to establish whether there is a link between the two.

Among older adults who were free of dementia, the team found a higher polygenic risk score was an indicator of worse memory and a smaller hippocampus at study baseline; the risk score accounted for 2.3 percent of the variance in memory and 2 percent of hippocampal volume variance.

Furthermore, during the 3-year study period, the researchers found that a higher polygenic risk score could be associated with increased decline in longitudinal memory and executive function among older adults, as well as greater clinical AD progression.

The team also found the polygenic risk score could be linked to overall clinical progression of AD.

Of 194 older adults who had normal cognitive functioning at study baseline, 15 developed mild cognitive impairment (MCI) or AD over 3 years, while 143 of 332 older participants who had MCI at the start of the study developed AD during the 3-year follow-up.

Overall, the researchers found that each increase in standard deviation of polygenic risk was represented by a 1.6-times greater risk of clinical AD progression.

Among the younger study participants, the researchers found a higher polygenic risk score could be linked to smaller hippocampal volume; the risk score accounted for around 0.2 percent of hippocampal volume variance.

The team says this finding indicates that genetic risk for AD is not specific to processes that occur in later life - such processes may begin in early adulthood:

"Overall, these analyses provide evidence that aggregate genetic risk of AD dementia exerts effects that are detectable before the clinical symptoms of dementia are present, even among young adults."

The authors note that their research only included a small number of participants, so larger studies are warranted.

Still, they believe their results could lead to better identification of individuals who are at increased risk for AD and other dementias long before symptoms arise.

"The goal of this type of research is to help physicians better identify those at high risk of dementia so that future preventive treatments may be used as early as possible," says Mormino.