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For Early Detection of Alzheimer’s Disease, Listen to Patients

April 20th, 2017

Early identification of disease often makes treatment easier and more successful. In recent years, scientists have developed a wide array of tests that use gene sequencing and other biomarkers to improve early detection of many diseases. These efforts are valuable, but often complex and expensive. Neuropsychologist Rebecca Amariglio has been focusing on a more straightforward and often overlooked strategy: asking patients whether they notice early symptoms of disease.

Amariglio studies Alzheimer’s disease, a devastating illness for which scientists are working to find early treatments. She has found that if you ask patients and their partners the right kinds of questions, you can identify people who are appropriate for clinical trials to test new treatments that could someday slow the progress of the disease and reduce some of the pain of dementia for patients and their families.

That may sound simple, but it’s not as easy as asking a single question about whether a patient is having memory trouble. Some declines in short-term memory and cognitive functioning are normal parts of aging. Many older adults worry needlessly that they are sliding into dementia, and that can cause other problems like anxiety. In fact, Amariglio says, “it has traditionally been a rule of thumb that if you’re worried [about your memory], you probably don’t have Alzheimer’s,” because people with advanced disease usually don’t have much awareness or insight about their condition.

Through her own clinical practice, Amariglio became interested in what people tell their doctors before they get to that advanced stage. How could she and other clinicians distinguish between people who are recognizing early symptoms and those who are just worried about normal aging?

Building on prior research, Amariglio, who is an assistant professor at Harvard Medical School, started looking at different types of questions and surveys about patients’ subjective cognitive complaints. The timing couldn’t have been better, she says, because an explosion of brain imaging techniques and the identification of specific genetic factors allow her to compare patients’ survey responses with these other indicators of disease risk. She also uses large studies that follow patients over time to see who does and doesn’t go on to develop the disease. The ideal method to determine the reliability of the subjective reports would be “a postmortem study to truly know what’s going on in the brain,” she explains, but for now, “the conjunction of the biomarkers and the longitudinal studies can tell us a lot about risk.”

That conjunction has led her to some promising results. She has found that people who report more concerns about memory on standardized surveys are more likely to have a certain kind of protein in their brains that is strongly associated with the disease. In fact, some of her studies have found that those subjective reports are more predictive of risk than cognitive testing performed by a clinician. She has also found that people who report more memory concerns over time are more likely to develop clinical impairment. The subjective reports are even better predictors of decline over time when you combine the person’s own report with that of a close family member or friend. On the surveys, people are asked questions like, “How is your memory compared to the way it was in the past?” and “When you actually forget in the following situations, how serious of a problem do you consider the memory failure to be?’’

Amariglio and her colleagues are now working to identify other useful questions. For example, she is concerned that the current questions do not sufficiently capture the complexity of everyday tasks individuals might perform (e.g., planning a dinner party) that might be the first sign of a change. She is also alert to the possible need to make the questions more relevant to non-White individuals, because current measures were largely developed in a White sample and it remains unclear whether these memory complaints are just as relevant and important to non-White groups.

Amariglio’s ultimate goal is to make it possible for “primary care settings to give patients a survey that could trigger further investigation [into disease risk], like a brain scan.” But she says, that is a long way down the road, and it is going to take the combined efforts of many scientists. “There is not going to be one single most effective measure for early identification,” she cautions, and “subjective cognitive complaints are one of an arsenal of things we will ultimately use to identify risk.” But, she adds, she likes the simplicity and straightforward nature of the measures she is using. Even more important to her is that this research is allowing doctors to “put the voice of the person high up” in the process of diagnosis and treatment. That’s not always the case in medicine, and Amariglio’s research is evidence that it should be.


Rebecca Amariglio is a recipient of the Federation of Associations in Behavioral & Brain Sciences (FABBS) Early Career Impact Award, which will be presented during the annual meeting of the Massachusetts Neuropsychological Society.

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