It used to be that people with dementia only went to the doctor at the urging of a family member who noticed changes in memory and behavior. But now that we consider Alzheimer’s to be a disease that begins decades before symptoms start to interfere with day-to-day life, researchers like Rebecca Amariglio, PhD, a neuropsychologist at Harvard Medical School and Brigham and Women’s Hospital, are saying that the best person to raise the red flag is the person experiencing symptoms. Amariglio is part of a team conducting the Harvard Brain Aging Study, and she has tracked how people judge their own cognitive impairment over time, and how that corresponds with biomarkers of Alzheimer’s disease like amyloid.
- Over time, people who had more concerns about their own memories showed steeper cognitive decline and greater amyloid burden, even if their tests were normal
- People with more education and greater cognitive reserve often test normally, but it’s because they’re able to compensate
- Memory tests that are individualized and comparable to an individual’s baseline are a better measure of cognitive decline
Being Patient: You study when people feel like they’re more forgetful, but they’re testing normal. What does that look like when someone comes into your office?
Rebecca Amariglio: I’ve been looking at this primarily in a research setting, where you can solicit it with a questionnaire that asks about memory complaints. It may not be something that somebody volunteers unless they’re asked. But with all the attention in the media on Alzheimer’s disease, people come into the clinic and discuss some of these difficulties that they’re having at a lower threshold than they used to. I have started to see more and more people who are noticing subtle changes, but then maybe perform normally on a cognitive test.
In some cases, it’s people who have what we call high cognitive reserve. One of our previous studies showed that the relationship between amyloid deposition and a greater number of complaints about memory was stronger in people with high education. It’s people that do well on cognitive testing who have more room to decline without it reaching a level of impairment.
Being Patient: So, those people are compensating for the decline they’re experiencing and testing normally, but they have a feeling that something is wrong.
Rebecca Amariglio: That’s right, a subjective feeling that they’re not where they used to be. It’s difficult to tease that out from normal aging because we know that everyone changes as they get older. But often people describe a more recent change that feels different from their peers. It’s not based on whether they slept well or in a period of stress—it’s persistent. You can’t tie it to other things.
Being Patient: What do they say that they’re forgetting?
Rebecca Amariglio: It really depends on the person. It could be the things you see so commonly in older age where people are having trouble coming up with names, finding that right word when they’re speaking or walking into a room and forgetting what they were doing. That’s a pretty common experience as people get older. It’s a bit beyond that—where if people are somewhat forgetful of their belongings, it’s just more intensified. I just recently saw a patient who fits exactly in the category I’m describing; high cognitive reserve, and he was mentioning he went on a trip and was having trouble remembering some of the people on the trip when he was talking to his significant other about it.
Or, it’s the sequencing of events in time, like, ‘Did I go on this trip before or after I saw my daughter?’ Stuff like that. Subtle, and maybe no one else would notice, but for that individual it feels like a change within themselves.
Being Patient: Tell us about what you’ve seen in the Harvard Aging Brain Study.
Rebecca Amariglio: Some of our initial findings showed that the greater number of complaints about memory on a subjective questionnaire—like forgetfulness, misplacing things, repeating themselves, getting disoriented—was associated with amyloid burden on a PET scan. Again, these are people who are clinically normal, so they do perfectly well on cognitive testing. We then found that people who had both amyloid burden and nerve degeneration had even more complaints—the idea being that these people are maybe even further along in the trajectory toward Alzheimer’s disease prior to impairment, but with biomarker changes.
When we looked at this over time, we found that people who are amyloid positive and have concerns when they’re testing normal tend to decline more steeply on their cognitive performance over time. That doesn’t mean they’re at the level of impairment, but they are changing on an individual basis.
We also found that people who are amyloid positive are increasing in their complaints over time. They’re coming in with more and more of these concerns. We added a new questionnaire to the Harvard Aging Brain Study that we think is more sensitive than some of the ones we’ve been using previously because it asks about change in the last year. Some of the questionnaires are asking about change over the last 10 years, and I think many of us would say, especially as you’re getting through your 60s and 70s, that you’ve declined over 10 years. So they may not be sensitive to something like Alzheimer’s disease.
Being Patient: For people with concerns, and especially for people with a high cognitive reserve, should they start taking a test in their 40s to get a baseline for their cognition?
Rebecca Amariglio: We’re not at the point where we universally suggest that. That may change if there are treatments available. To be honest, right now if you do that and you see a change, there’s not a whole lot we can do. But just like in cancer and other things, if there are treatments, then there might be a much greater impetus to start tracking these things earlier on and intervening earlier.
Being Patient: I’ve read a lot that people only realize they have dementia when a family member is concerned about their memory. But it sounds like you’re saying to listen to those really early signs and your intuition about your own brain.
Rebecca Amariglio: It’s exactly right that it used to be the rule of thumb—that if you weren’t worried, that that was actually more concerning. At the stage of dementia patients think they’re fine, when they in fact have significant memory problems. Now when we use the term Alzheimer’s disease, we’re including the pre-clinical stage. The complaints seem to be informative at that pre-clinical stage, and even into mild cognitive impairment. There is not this lack of insider awareness until they’re getting close to the stage of [having] dementia. People recognize that they’re having difficulties.
I would absolutely encourage people to pay attention to this, but we do know that they’re related to other things like depression and other things. It’s just important to bring it up with the doctor and then make a decision on how to go forward from there.
This interview has been edited for clarity and length.