As part of our BrainTalk series, Being Patient spoke with Dr. Claudia Kawas, co-lead investigator of the 90+ Study, about the complex pathothologies of dementia and how people can build resilience against the disease.
While scientists are gaining a better understanding of the keys to healthy aging, they are also grappling with the complexities of dementia in all its different forms. Research in the lifestyles and brains of people aged 90 and older are yielding critical insights on habits that lead to a longer life and the different pathologies involved in dementia.
Being Patient spoke with Dr. Claudia Kawas, professor of neurology, neurobiology and behavior at University of California, Irvine, and co-lead investigator of the 90+ Study, about how some people are more resilient than others against dementia.
– Education appears to be a critical factor in building people’s resilience against dementia. For one, it is associated with behaviors that promote brain health, which in turn, may influence the risk of dementia. Meanwhile, the more people learn, the more cognitive reserve they may have as a buffer against the disease.
– Social engagement is one of the key lifestyle factors that is linked to longevity.
– People can experience symptoms similar to those of Alzheimer’s, even without the presence of beta-amyloid plaques and tau tangles in their brains. After all, TDP-43, a biomarker of a newly described form of dementia known as limbic predominant age-related TDP-43 encephalopathy (LATE), can be present in people’s brains and impair the brain’s memory center.
Being Patient: What’s the quality of life of people who are aged 90 and older?
Dr. Claudia Kawas: It really spans the whole range. Unfortunately, variability is the hallmark of aging. You have people at one spectrum who are quite impaired, whether it be [the] ability to walk or think. At the other end of the spectrum, you have people who are remarkable, flying all over and visiting [people], driving, doing artwork, volunteering — all sorts of things. And [there’s] everybody in between. We know which end of the spectrum we want to be at, so the question is how to move all of us over to the good end.
Being Patient: How are some people able to live without dementia even though their brains are filled with beta-amyloid plaques and tau tangles?
Dr. Claudia Kawas: One possibility is that if they’ve lived longer, they might have developed dementia. Another possibility might be that the toxic effects aren’t for some reason affecting them. Now, we’re realizing that there do appear to be some people, particularly among the oldest old, who [appear to be] resilient. That is, they can have all these things in their head, and they’re still fine.
Being Patient: What contributes to people’s resilience? Could it be that certain genetics protect our brain from neurodegeneration?
Dr. Claudia Kawas: It could be. But it could also be an environmental resiliency. Education appears to be related to resiliency. Maybe it’s the effects of early life development and education that carry forward with behaviors … Some people think it might also be that when you get educated, you can hide the signs [of dementia] for longer.
Being Patient: The case of Ted Rosenbaum from the 90+ Study was featured in the CBS show 60 minutes: He had dementia even though he didn’t have plaques in his brain. What could have caused his symptoms of dementia?
Dr. Claudia Kawas: The most likely explanation in his case was something that is now being called LATE — limbic predominant age-related TDP-43 encephalopathy. People [with LATE have symptoms that are] very similar to Alzheimer’s disease. [Alzheimer’s] is almost always the diagnosis they receive during life. They tend to have memory problems. They tend to progress less quickly. They have a slower rate of decline and lower levels of impairment, at least in some cases.
We now realize that [TDP-43] happens in a lot of disorders, [including] ALS, where it was first identified. Frontotemporal dementia is associated with it. Many Alzheimer’s patients also have it. You can have Alzheimer’s alone. You can have [LATE] alone. You can have them both together.
Being Patient: What is TDP-43?
Dr. Claudia Kawas: It’s an abnormal protein. It’s a hyperphosphorylated protein that’s associated with neurodegeneration. In that way, it’s very similar to an amyloid plaque or a tau tangle, which are the abnormal proteins we use to identify Alzheimer’s disease.
[LATE] basically identifies another disease process. For example, when we talk about Alzheimer’s disease, we say [people] have amyloid [and] tau. If we’re talking about Parkinson’s, we talk about the alpha-synuclein protein, which is what’s in Lewy bodies. A lot of people think that this entity of LATE is another thing along the same lines: You might have [TDP-43] as the associated abnormality. Maybe stopping that phosphorylation will help and maybe it won’t.
The same problem we have now with [TDP-43] is the one we have [had] for Alzheimer’s disease through my entire career, until recently. Now, I can get an idea if you have an amyloid plaque or a tau [tangle] in your head [through] a PET scan, or a spinal tap, or most recently some blood assays. But I can’t do any of those things yet for [TDP-43], although people are working on it. [It] would help a lot to study it more.
There’s some optimism that needs to be said here. It turns out that over the last 20 years. The age-specific risk of dementia has gone down. If you were an 80 year old 20 years ago, your likelihood of having dementia at [one time point] was much higher than it is if you’re an 80 year old now.
The real interesting part about that is what made it go down, because the only thing I know for sure is none of our drug trials were successful. There is no drug that made it go down. [There are] other things that are happening, some of which I think have to do with lifestyle [and] management of things like hypertension and cholesterol. The fact that it’s down [is] very encouraging [for] us, because it should tell us that there’s factors that we may be already manipulating, and there’s probably more.
Being Patient: We have all experienced a great deal of isolation during the pandemic, and we know that social isolation is detrimental to brain health. How are your study participants doing during the pandemic?
Dr. Claudia Kawas: It’s been a long year, and a very isolating one for our 90-year-olds. About a month ago, when we temporarily reopened the clinic so that they could come in for it in-person visits, out of the first 15 people we called, 14 immediately were scheduled and came in. We miss seeing them and they miss seeing us.
[The effect of social engagement] is always minimized in our head. It doesn’t sound real scientific or it’s not a pill. But engaging with other people probably contributes more to brain health than we generally admit … It’s a very important kind of brain activity.
The interview has been edited for length and clarity.
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