For years, doctors have dismissed patients' worries about mild slips of memory as a normal part of ageing. Now, as the focus in Alzheimer's research moves toward early diagnosis, researchers are looking for ways to tell whether some of these "senior moments" are an early sign of the disease.
The idea is so new that scientists can't even agree on what to call these memory complaints among people who are still cognitively normal.
But experts gathered at the Alzheimer's Association International Conference in Boston say evidence is growing that it may be possible to couple certain patterns of memory lapses with genetic markers or changes in the brain and spinal fluid to better predict which individuals are displaying the earliest symptoms of Alzheimer's.
Finding people who are just beginning to develop the disease is important as companies struggle to find treatments that can prevent or delay the disease. In the past 12 months, several high-profile clinical trials testing drugs in people with mild to moderate Alzheimer's failed to show a benefit. Scientists believe that may be because the drugs are being tried too late, when the disease has already killed off too many brain cells.
Last week, Eli Lilly announced it will start a new clinical trial of its experimental Alzheimer's drug solanezumab focusing only on patients with mild signs of the disease, after two late-stage studies of the treatment in people with more advanced disease failed to show a benefit.
Dean Hartley, director of science initiatives at the Alzheimer's Association, said scientists are just beginning to quantify whether anecdotal reports of memory loss have any bearing on whether a person ultimately develops dementia.
The difficulty is that many things can cause temporary memory slips, including sleeplessness, depression, stress and some medications. "The question is which ones are indicative of underlying pathological changes," he said.
To study the problem, Dr Rebecca Amariglio, a neurologist at Brigham and Women's Hospital in Boston, took a sample of 189 clinically normal adults over age 65 and asked them questions about their memories.
Researchers also did brain scans using a radioactive tracer that can detect the presence of a protein called beta amyloid that is believed to be an early sign of Alzheimer's disease.
The team found that the people who reported the most trouble with their memories also had amyloid buildup in their brains. "Subjective concerns may be an early indicator of Alzheimer's pathology," said Amariglio, who is presenting her findings at the Alzheimer's meeting this week.
Questions used by the team covered a whole range of common memory issues, such as misplacing belongings or forgetting details of conversations.
Such lapses can of course be just an artifact of people leading busy lives. The trick is sorting out which memory complaints are meaningful and which aren't.
Dr Richard Kryscio, an expert in biostatistics at the University of Kentucky, has been tracking memory complaints in more than 1000 cognitively healthy people in their 60's and 70's for more than a decade.
People who sign up for the study visit the centre once a year to take a battery of cognitive tests. Each person is asked whether he or she has noticed any decline in memory since the last visit.
Kryscio reported results of the first 531 people at the Alzheimer's meeting. The group started the study at an average age of 73.
Over the course of 10 years, more than half of study participants said they noticed a change in their memories. Among this group, individuals were also twice as likely to be diagnosed with dementia or a precursor to dementia called mild cognitive impairment (MCI) in follow-up visits as those who reported no change.
A separate study from Cecilia Samieri of the Research Center Inserm in Bordeaux, France, and colleagues at Brigham & Women's also found a strong correlation between self-reports of memory loss in individuals with a gene defect called APOE4 that is known to raise the risk of Alzheimer's.
Amariglio said the findings are more important for research than for doctors, because there are no proven treatments to prevent the development of Alzheimer's.
Dr Creighton Phelps of the National Institute on Aging said in the past that Alzheimer's researchers have written off people's reports of memory loss among the cognitively normal as a concern of the "worried well", but that now they are starting to listen more carefully.
"Over time, these self-reports do lead to some measurable declines," he said.
That doesn't mean that people who occasionally lose their keys or forget where they parked the car should go rushing to their doctors, said Dr Ronald Petersen, an expert in early Alzheimer's disease at the Mayo Clinic in Rochester, Minnesota.
In a study his team is doing of cognitively healthy people, 80% of normal people aged 70 and older will say their memory is not what it once was.
"What this research is trying to do is carve out that subset of people who are really telling us something that might be important."