Alzheimer’s disease affects more than 6 million Americans. Despite years of intensive research, we still lack effective tools to treat this devastating form of dementia. The best medicine can offer at this point is an early diagnosis, when medications can still alleviate symptoms and patients and families can be coached on how to cope with increasing cognitive impairment down the road.
When a drug controversially received FDA approval last year to treat Alzheimer’s with no evidence that it actually slows the progression of dementia, Maria Glymour, PhD, was among those who argued that the research approach to Alzheimer’s disease needed an overhaul. We are unlikely to make breakthroughs on this difficult disease if we continue to focus on physiological and cognitive effects that occur well into disease development.
In a new study with Glymour as senior author, research data analyst Scott Zimmerman, MPH, looked for the earliest age at which people show cognitive impairment. The work suggests it may be possible to identify the earliest signs of Alzheimer’s dementia by age 47. The paper was published today in JAMA Network Open.
“In order to fully understand how Alzheimer’s develops we need to look at what’s happening to people much earlier in life, well before the disease begins to impact daily life,” Zimmerman said.
Here’s how the study worked. More than 400,000 people over age 40 who are part of the UK Biobank research program participated in a battery of established cognitive tests, and all had shared their DNA for research. Zimmerman compared the scores of people with what previous research has characterized as a high genetic risk of Alzheimer’s disease to the scores of those without the genetic risk factors. Those with high-risk genes – a group that statistically would include a disproportionate number of people already developing Alzheimer’s disease – had lower scores than others of the same age on 13 cognitive measures by age 56. They had lower scores on 9 of the measures by age 47. The large sample size made even small differences detectable.
Previous work to try to find signs of Alzheimer’s have generally looked at those over age 65, blinding themselves to potentially earlier signs.
“Even though Alzheimer's dementia is not usually diagnosed until much later ages, these findings suggest the very earliest cognitive changes may begin when people are in their late 40s,” Glymour said. “That means dementia prevention should be a priority for middle-aged – or younger – adults. It also means that for us to study this disease, we need to start research at much younger ages. If we are studying people in their 60s and 70s, we are probably focusing on a middle period in disease development, not the period when the disease begins.”
The research team also included professors Rebecca Graff, Thomas Hoffman and Willa Brenowitz and postdoc Sarah Ackley.
UCSF photo by Majed