Doctors who tell their aging patients not to fret about memory lapses may be doing them a disservice, according to new studies that suggest they may be the earliest discernible signs of Alzheimer's disease.
The condition, dubbed subjective cognitive decline, is one of the hottest new areas in dementia research. Five reports presented at the Alzheimer's Association meeting in Boston found healthy people who say their thinking is growing cloudy may already have changes in their brains and are twice as probable to be subsequently diagnosed with a cognitive disorder.
For years people have complained about their memories and doctors have told them not to worry, said Creighton Phelps, acting director of the dementias of aging branch at the National Institute on Aging. It's being taken more seriously as an early warning signal, and gives investigators a potential screening tool to identify those who will progress more quickly, he said.
"The hardest part is deciding what is normal aging and what's abnormal," said Phelps, who wasn't involved in the research. "We all lose our car keys. We've been doing that all our lives. If you forget how to use a key or you find it in the refrigerator, that should make you stop and think."
The results have immediate applications for researchers who are beginning studies aimed at slowing or stopping Alzheimer's disease before full-blown symptoms appear, said researcher Rebecca Amariglio, a neuropsychologist at Brigham and Women's Hospital in Boston.
Amariglio and her colleagues developed a survey with more than 100 questions and gave it to 189 healthy volunteers with no history of neurological disease. They also scanned their brains for amyloid, a protein that builds up in Alzheimer's disease patients. Participants who reported the most concern with their memory, or who started struggling with mental activities like prioritizing tasks, had the most amyloid, the study found.
"People's self-reports about their memory may be an early indicator of disease, well before other tests," Amariglio said in a telephone interview. "These results shouldn't scare people, so that if they have minor blips in their everyday lives they get freaked out," she said. "But now is an exciting time to enroll people in drug trials, before they show symptoms."
Eventually the questions asked may be fine-tuned so that doctors and researchers can use to them during routine exams to identify patients who are at the earliest stages of the disease, before overt symptoms begin to appear.
An international group of experts, led by Frank Jessen from the University of Bonn in Germany, devised a framework for future research. Their guidelines lay out terms and methods that should be used to coordinate efforts around the world and can indicate whether a person's complaints are linked to an early stage of the disease, Jessen said in a statement.
Richard Kryscio and his team at the University of Kentucky delved deep into the brains of volunteers to confirm the complaints they reported reflected disease. They asked 531 volunteers if they had memory changes during annual exams that were conducted for a decade. Slightly more than half said yes. A diagnosis typically came six to nine years later.
"A person who said yes down the road was three times as likely to have an event, mild cognitive impairment or full-blown dementia," said Kryscio, chairman of biostatistics in the College of Public Health, in an interview. "By no means is it a sure sign you'll get an impairment -- and it takes time, but it does seem real."
Some patients in Kryscio's study were found to be on a fast track, hitting dementia directly and more quickly. They were more likely to be women, overweight, with high blood pressure and a family history of dementia.
All the volunteers in the study agreed to donate their brains to science. Half have died. Autopsy results confirm that few of those who consistently said they were fine ultimately had signs of Alzheimer's, he said.
The findings may be strongest in people who experience declines in memory and carry genetic risk factors that predispose them to Alzheimer's. A study of 3,861 nurses found those who had a concern about even one possible symptom were likely to have their verbal memory decline within six years if they also had the ApoE4 gene linked to the disease.
The increased risk in volunteers without the gene appeared only in those who had three or more concerns out of a list of seven specific memory symptoms.
"ApoE4 carriers with self-assessed memory symptoms have accelerated verbal memory decline and may therefore be an interesting and easily identified target population for research on early interventions," she said.
People who notice a change in themselves or their loved ones should get a health checkup, said Heather Snyder, director of medical and scientific operations at the Alzheimer's Association. The signs may be different for everyone and the key is looking for trouble in what used to be normal patterns.
"If it seems like it is getting in the way of your life, and it's worrying you, get it checked out," said the NIA's Phelps. "Even if you test positive, you still have a number of years. People with Alzheimer's disease can still function, even if not as well as they once could. Perhaps you go to a simpler lifestyle that isn't so demanding and enjoy the time you have."