People carrying a gene linked to late-onset Alzheimer's disease have a higher risk of subtle memory loss as early as their 50s, far sooner than mental decline shows up from normal aging, a study found.

Tests given to 815 research participants in Arizona found 317 carried one or two copies of the gene, known as apolipoprotein E or APOE e4. Memory and IQ tests given over five years showed some of those with two copies of the gene had a higher risk of subtle memory changes as soon as their 50s compared with people who didn't carry the gene. Those with one gene copy started showing a higher risk of mental decline in their 60s, according to a study published today in the New England Journal of Medicine.

Normal aging can cause mild memory loss typically as people reach their 60s, 70s or later. The APOE e4 gene is a known genetic risk factor for Alzheimer's disease and may account for as many as half of all cases known as late-onset after age 65, the researchers wrote. The findings suggest that people with the APOE e4 gene experience more rapid memory loss and reduced learning efficiency than others in their age group, said lead study author Richard J. Caselli, neurologist and chairman of the neurology department at the Mayo Clinic Arizona in Scottsdale.

"This study moved the bar to a younger age range," Caselli said. The findings may lead to more preventive measures, aimed at younger people who show these signs of memory decline but haven't yet been diagnosed with Alzheimer's, he said.

An estimated 5.3 million people in the U.S. suffer from Alzheimer's, a progressive disease that destroys brain cells and is the fifth leading cause of death among individuals 65 and over, according to the Alzheimer's Association.

Healthy People Recruited

Using local advertisements, the researchers recruited mentally normal subjects, who were divided into groups of non- carriers, carriers with one copy of the gene and carriers with two copies of the gene. Those who had suffered from a stroke, head injury or a serious, active psychological problem were excluded. During the follow-up 15 subjects were barred because they met published criteria for some form of dementia or mild cognitive impairment.

The participants who were carriers were generally younger than those who did not carry the gene. A majority of subjects were over the age of 50 years, creating a lopsided study population, the researchers said.

"It gave us power in the 50's age range, but not with earlier groups," Caselli explained.

Bill Thies, head of the Alzheimer's Association, said the study may prove useful for efforts directed to slowing disease development. "While it's not the first study to illustrate early cognitive changes in APOE carriers, it is one of the more comprehensive," he said. "This study is important as we develop a disease-modifying drug because it helps us pick an age range to focus on."