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In this episode Matt and Lauren will speak with Dr. Marcia Pescador Jimenez, an Assistant Professor in the Department of Epidemiology at Boston University whose research focuses on understanding the relationship between exposure to green space and health outcomes (including hypertension and cognitive measures). Emerging research has shown that midlife risk factors may delay or even prevent the onset of dementia later in life - among these include physical activity and social interaction. It’s not a stretch to imagine how a person’s environment may impact behaviors such as physical activity. For instance, there are places that lack sidewalks and parks that make exercising exceedingly difficult. Among environmental epidemiologists, there is growing interest in understanding how the built and natural environment influence our behaviors that, in turn, influence our health.   

We encourage you to listen to this episode while on a walk outside!  

More resources

Dr. Marcia Pescador Jimenez Faculty Profile 

Article Referenced in Podcast:  

Pescador Jimenez M, Wagner M, Laden F, Hart JE, Grodstein F, James P. Midlife Residential Greenness and Late-Life Cognitive Decline among Nurses' Health Study Participants. Environ Health Perspect. 2024 Jul;132(7):77003. doi: 10.1289/EHP13588. Epub 2024 Jul 17. PMID: 39016600; PMCID: PMC11253812. 

Nurses’ Health Study 

The social engagement scale that was referenced in the podcast is called the “Berkman-Syme Social Network Index”

Transcript

Matt Davis:

Emerging research has shown that midlife risk factors may delay or even prevent the onset of dementia later in life, and among these include things like physical activity and social interaction. It's not a stretch to imagine how a person's environment may impact behavior such as physical activity. For instance, there are places that lack sidewalks and parks that make exercising difficult. Among environmental epidemiologists, there's a growing interest in understanding how the built and natural environment influence our behaviors that in turn influence our health. There's some theory too that suggests greenspace in particular may help reduce stress and improve air quality.

In this episode, we'll discuss a recent study that examined the association between access to greenspace and late-life cognitive decline. I'm Matt Davis.

Lauren Gerlach:

I'm Lauren Gerlach.

Matt Davis:

And you're listening to Minding Memory.

We're joined today by Dr. Marcia Pescador Jimenez. Dr. Pescador Jimenez is an Assistant Professor in the Department of Epidemiology at Boston University. Her research focuses on understanding the relationship between exposure to greenspace and health outcomes. Among these include things like hypertension and cognitive measures. She's here today to speak with us about her recent study.

Marcia, welcome to the podcast.

Marcia Pescador Jimenez:

Thank you. Hi, everyone. It's a pleasure to be here. Thank you for inviting me.

Matt Davis:

Dr. Pescador Jimenez was a lead author of a study titled, "Midlife Residential Greenness and Late-Life Cognitive Decline Among Nurses' Health Study Participants" that was published in the journal Environmental Health Perspectives. We'll include a link to the study attached to this episode. Make sure to check it out.

So as you probably know, this is a research podcast, so we always like to kick things off with just getting our definitions straight. So as a person who studies the health impacts of environment, how do you define greenspace?

Marcia Pescador Jimenez:

I think the way that we generally define it is any type of area covered by vegetation, by green vegetation, and by these I mean it could be trees, grass, flowers, shrubs, etc. So I'm not necessarily going to look at deserts or any type of water either. That's a separate area of research.

Matt Davis:

Is there any difference between or is there any point in differentiating between greenspace and parks?

Marcia Pescador Jimenez:

No, I think parks are considered greenspace depending on the metric that you use. For the purposes of these analyses, we use satellite-derived metrics of greenness, which measures the amount of vegetation in a given pixel and that vegetation could be in a park or in a walking path. So we don't necessarily know how to differentiate the types of greenspace areas. We just know that there is some greenness around it, if that makes sense.

Lauren Gerlach:

So it seems like there's been growing evidence that being immersed in nature is good for your health and it's been linked to improvements in sleep, blood pressure, and even associated with decreased mortality. Can you tell us a little bit about the theory or link between living near greenspace and health outcomes, and moreover, cognitive decline?

Marcia Pescador Jimenez:

Yes, absolutely. So the general hypothesis is that greenness can benefit health outcomes through four major pathways. The first is through reducing stress, psychological stress. The second is through reducing exposure to other detrimental exposures such as air pollution or noise. And the last two are through increasing either opportunities for physical activity and also increasing opportunities for social connection. The idea is that greenness through either of those pathways would lead to eventually better health outcomes.

Matt Davis:

I'm just curious, how did you personally get interested in studying greenspace?

Marcia Pescador Jimenez:

So, I remember I was a doctoral student actually, and I met with my mentor and we were strategizing about specific aims for the F31 grant that I submitted and eventually got funded, and because I'm originally from Mexico City and I was raised and grew up there and I was exposed to air pollution and traffic and then I went to live in Belgium to study a master's degree, and in Belgium, the sky was gray, there was nowhere pollution, but it was rainy most of the week and people would commute to their jobs in bicycles. It was a totally different environment. So I had recently migrated to Boston from Belgium, and I just had these very fresh in my mind. I was like, "There's something about the place where you live that affects your health and wellbeing."

So I was trying to look at different aspects of neighborhood and what matters the most, and I was particularly interested in neighborhood deprivation, neighborhood socioeconomic deprivation. And my advisor at the time asked me, "Okay, but what would be the intervention? If you were to find that there is a significant association between neighborhood socioeconomic deprivation and cardiovascular risk," which was my outcome of interest, "what would be the intervention? It's like to give more money to neighborhoods? What would you do?" And that really got me thinking.

So then we started looking at natural environment and greenspace, which was much more of a clear intervention. If we were to find that greenness is positively associated with health, planting trees or grass seemed like a more straightforward way to improve health outcomes at a wider scale, and also to help the environment. Right? Greenness is just good for everyone, or at least that's how I want to think about it. That's really how this whole idea started.

And then for my postdoctoral studies at the Harvard School of Public Health, I really delved into greenness. I started looking at the satellite-based metrics with my mentor at Harvard, and then the pandemic hit, and I was at home with a newborn and a three-year-old and I was not doing well. So I essentially started going outside for a run or for a walk in the greenspace areas that we have around, I live in the suburbs, and I just felt almost immediately happier and calmer. And I just realized that it made sense, it made total sense, and my whole PhD was like, "Okay, yes, this was good!"

So that's a long answer, I guess, to why I'm doing what I'm doing.

Matt Davis:

That's super interesting. And so I'm assuming that you consider greenspace as a modifiable thing, right?

Marcia Pescador Jimenez:

Exactly.

Matt Davis:

Yeah, okay. And it sort of explains too, I don't know, I've always had a lot of respect for interior design people that bring a lot of natural stuff into the house and all that kind of stuff. It does matter, doesn't it?

Marcia Pescador Jimenez:

Absolutely, yeah. I guess this is not based on scientific research, but if I see my house clear of clutter and I have plants everywhere also inside, it just makes me feel calmer and I'm a better person because of it and a better mom to my kids and I enjoy more of everything of what I'm doing, so yeah.

Matt Davis:

This is a dementia-based podcast, as you know, so I think a lot of our listeners are pretty familiar with some of the big ones, but likely less familiar with the Nurses' Health Study. I was wondering if you could tell us a little bit about the study.

Marcia Pescador Jimenez:

Yeah, so this study is a fantastic research that I was able to work on during my post-doctoral study. The Nurses' Health Study I includes about 121, almost 122,000 participants, and they started in 1976 with married female registered nurses. They were about 30 years of age at baseline, and they were originally located across 11 states in the US. But throughout time, they've moved around the country and they are now scattered all over the country so now it's a nationwide study. And the participants addresses have been geocoded, which means that we assigned a latitude and a longitude to the residential address since 1986, which gives a few decades of environmental exposure data. Participants have completed questionnaires since baseline every two years on medical history and health-related behaviors with a follow-up of more than 90%, which it's very impressive.

Matt Davis:

And is it women only?

Marcia Pescador Jimenez:

Yes. There are a few limitations, as to every cohort study, I guess. And I guess that's one of the limitations that it's women only. It's mostly white population and it's also of high socioeconomic status. You know, these are highly educated white women.

Matt Davis:

But the goal of it, and correct me if I'm wrong, is around understanding women's health, right? It's not necessarily about nursing and occupational issues.

Marcia Pescador Jimenez:

Exactly, yeah. I believe the American Journal of Public Health has a whole issue focusing on the Nurses' Health Study, and really, the knowledge that researchers have gained due to the Nurses' Health Study participants. So yeah, it's a whole giant study that has brought a lot of good things to us.

Matt Davis:

And what specifically, being a dementia podcast, can you talk a little bit more about the cognitive measures that they have and are they on everyone in the study?

Marcia Pescador Jimenez:

Yes. I'll talk about the cognitive measures in Nurses' I. There's a Nurses' Health Study II, but there are some others in Nurse's Health II, and I can briefly talk about those too.

In Nurses' Health Study I, the assessments of cognitive function were validated telephone interviews that have been validated before, and they initially administered the Telephone Interview of Cognitive Status, or TICS. I pronounce it TICS, I'm not sure if that's the correct pronunciation. It's a telephone adaptation of the Mini-Mental State Exam, and then we had five more cognitive tests. We had delayed recall of the TICS, 10-word list, the East Boston Memory Test, immediate delayed recalls, as well as a category fluency and a digit span backward. And I think the idea of this is that these cognitive tests are also repeated throughout time, so we were able not only to assess cognitive function at a single time point, but we were also able to assess cognitive decline over time.

Lauren Gerlach:

And for your study, how exactly did you look at cognitive decline? How did you compare the scores over time?

Marcia Pescador Jimenez:

Yeah. So we created, because the cognitive tests are scaled differently from each other, we use Z-scores to create composite measures, and then we created a global composite score, which was calculated as the average of all Z-scores to evaluate overall cognitive functioning. But then we were also interested in certain cognitive domains, so we created composite verbal memory score that was also derived by averaging Z-scores of the immediate and delayed recalls of the EBMT and the TICS 10-word list component. And while our main findings for this paper are based on the global composite score, we also evaluated the verbal memory score as a secondary outcome, which was strongly associated with Alzheimer's dementia in particular.

Lauren Gerlach:

So I think your study focused specifically on midlife exposure to greenness. I'm wondering if there's any information about earlier-life exposure or if you don't have as much early-life exposure, can you still make up for it later? I'm just wondering what we know about that.

Marcia Pescador Jimenez:

I love that question. So to be able to actually study the full lifetime exposure, it would be very hard because you would essentially need a cohort of participants followed through birth all the way to older adulthood and we don't have that type of money. But I've actually done some work before in a preconception cohort in Project VIVA during my postdoctoral studies also at Harvard, and Project VIVA followed pregnant women and then they followed the offspring.

And in that study, what we did is, again, we linked greenness metrics to the children based on the place of birth and then an early childhood and mid-childhood and early adolescence. And we were precisely interested in, during that time, is there a sensitive period of exposure to greenness that might matter most for cognitive health in early, not adulthood, but adolescence. Sorry. And what we saw was that early childhood actually was a sensitive period of greenness exposure where having higher greenness exposure during early childhood was associated with better cognitive scores at early adolescence, whereas greenness exposure at birth or at mid-childhood was not necessarily so.

So that's just a hint to see that there might be some sensitive periods. In this study, we precisely wanted to see if maybe mid-adulthood was a sensitive period, and it suggests that it does indeed.

Matt Davis:

This is totally in the weeds, but I love it whenever I see Z-scores because I can make the point to my students that they actually are useful and they're not just for stats courses. Did you do Z-scores across all time points or at each time point?

Marcia Pescador Jimenez:

Yes, we did Z-scores at each time point, and then we follow them across time. Does that make sense?

Matt Davis:

Okay. At each time point, you had a Z-score basically for relative performance?

Marcia Pescador Jimenez:

Exactly, yes. Yeah.

Matt Davis:

Okay. So just circling back, you mentioned that you use some satellite data. That is not something that we talk about very often on our podcast. So I was wondering if you could talk a little bit more about what that whole thing is about and where you could get access to satellite data and all of that?

Marcia Pescador Jimenez:

Yeah, of course. Happy to. I'll actually talk a little bit about our biology classes. As you may recall, the plants go through a process of photosynthesis. Satellite data actually is capturing that process. What happens is that leaves absorb solar radiation in the visible photosynthetically active wavelength, and they also scatter solar radiation to avoid overheating in the near-infrared wavelength. And the normalized difference vegetation index, or NDVI as we call it, is based on the ratio of precisely the near-infrared to visible light. And this way, we get a nice objective measure of vegetation quantity.

To walk through how we do this is that we have a geocoded address of a participant, so we map them in a map, and then we overlay the raster of NDVI, and then we assign the value of NDVI to the participant based on the pixel that their home is in.  NDVI goes from -1 to 1 with more positive values indicating more vegetation, and then for this study, we actually used NDVI from 1986 up to 1994, so we had about a decade of cumulative exposure to greenness.

And the way to get satellite-based data is actually really simple. You know back in the day, for instance, when I was doing my doctoral degree, this would take years, but now we use Google Earth Engine and they have code readily available for you. They have even examples of code, so you can just run the code, you can start downloading satellite-based data for whichever study that you may want to do.

Matt Davis:

Wow. So in theory, it's publicly available?

Marcia Pescador Jimenez:

It is publicly available, yeah. It's very heavy. Sometimes we have terabytes of data, especially if you need greenness exposure for the full country for different years. We also, I should mention, we also usually focus on the summer, which it's the height of variability for greenness, but we also do sensitivity analysis for greenness at winter, at fall, spring, and also an annual average. So we're talking about a lot of data.

Matt Davis:

I'm curious, your colleagues doing environmental studies, are they doing similar things in other... I mean, are they using satellite data in other ways for epidemiology research?

Marcia Pescador Jimenez:

Yeah. A lot of us use satellite data for greenness studies, and the way that it works is that we can also use different scales, like I use 30-meter resolutions for this study, but we can also create different buffers. I think we use 90 meters to represent the immediate exposure outside of your residence, but we can also look at 270 meters to represent the walkable distance, and then maybe 1,000 meters to represent the neighborhood exposure to greenness.

I'm also starting to use satellite data for other projects. One thing that we're potentially going to be using these for is to measure ambient temperature. The ERA5 data provides aggregated values for each day for seven climate areas. There's a lot of use for satellite data.

Lauren Gerlach:

So if a nurse moved during the study, were you able to then readjust based on their new location and adjust greenness for where they were at different points of time?

Marcia Pescador Jimenez:

Exactly, yeah, because as long as we have the updated address, we can just geocode it and reassign the value, the NDVI value, to the most updated address. So for each year, we had the most updated NDVI value. And we actually also run some sensitivity analysis to focus only on participants that had been living at their residence for longer than five years, just to make sure that we are not biasing our results anyway or other, and the results were consistent.

Lauren Gerlach:

Could you give us a high-level overview of what you found?

Marcia Pescador Jimenez:

Yeah! So overall, what we saw was that greenness slows down cognitive decline, and it does so, more importantly, in vulnerable subgroups of the population. So essentially, we observed that greenness exposure was associated with a .004 unit of slower annual rate of cognitive decline. And just to understand what that really means, for comparison, we found that 1 year of age was related to a -.006 mean annual difference for global cognition in the full sample. So if you translate these, it just means that higher midlife greenness appeared equivalent to slowing cognitive decline by about eight months.

Lauren Gerlach:

I mean, that's pretty amazing. I think of it as a clinician, and when we talk about medication classes like cholinesterase inhibitors or medications that we prescribe to presumably try to slow cognitive decline, that's about the same time span that we give, about a six to eight-month period of decline. So pretty-

Matt Davis:

That's super interesting.

Marcia Pescador Jimenez:

Yeah, that's amazing.

Lauren Gerlach:

Yeah. Really, that sounds about equivalent.

Matt Davis:

Your team also looked at the interaction between APOE gene for Alzheimer's disease and greenspace exposure. What was the rationale for looking at this and what did the analysis show?

Marcia Pescador Jimenez:

We ran some stratified analysis, and in every study that we do with greenness and health, we try to stratify our results either by race and ethnicity or by neighborhood socioeconomic status, and in this case, we also had access to APOE for status. And the idea of doing this is to take a look at vulnerable populations. So again, thinking about interventions and just to make it as narrow as possible so that it's easier. If we were to intervene and say, "Okay, let's find more trees or more grass," where should we start?” And I think that's the idea of stratifying.

And what we found with APOE for carriers was that greenness was associated not only with a higher cognitive function at baseline, but also with a slower cognitive decline across time. Whereas for non-carriers, the results attenuated a little bit. So these just, to me, made sense because it means that for higher-risk populations, greenness might be particularly important, or greenness exposure might be particularly important.

Matt Davis:

So I'm curious, the causal mechanism is a little bit complicated, right, when you talk about environmental things like greenspace? I'm curious about your team's decisions in regards to what factors you ended up adjusting for in your models. I was wondering if you can talk about that a little bit.

Marcia Pescador Jimenez:

Yeah, I can talk about the decision-making process. I think the way that I try to do this in every study, and I also ask my mentees to do this, is first to look at previous literature and see what other studies have adjusted for in their analysis. But also, and I think this is the least-favorite part of my students and mentees, is to actually draw a DAG and choose the confounders based on a DAG. That's essentially what we do. We go through the literature and look at confounders that have been previously adjusted for in the model, and then based on that, we draw our DAG and we make sure that it makes sense, and that's really it.

The other thing that I want to point out is that we adjust for confounders in a hierarchical manner, meaning that the models will be nested within each other. For instance, if model one adjusts for age and race, then model two would be adjusting for age, race, and education, say. And the idea of doing that is just because I'm interested in seeing how the estimate for greenness change across models, and yeah, I think that's my favorite way of presenting the results.

Lauren Gerlach:

There was a couple unique covariates that I'm just curious how you quantify as someone who doesn't routinely include these things in our models, although probably should. For instance, air pollution isn't something that I'm too familiar with on how you quantify or access data around that, and then I was a little curious about the social engagement piece and if that's something unique to the Nurses' Health Study or how you use that data.

Marcia Pescador Jimenez:

Yes, absolutely. So for air pollution, I wasn't part of the team that built that metric, so I don't feel confident enough to talk about how that metric was built, but air pollution is a major confounder in the association between greenness and cognitive health. It's one of the risk factors. I actually think it's very interesting that air pollution is the only environmental risk factor that is listed in the Lancet risk factor publication. So anyways, air pollution has to be there, for sure.

And then your question on social engagement, I think the idea to look at social engagement was to try to get at the mechanisms through which greenness would be associated with cognitive function and cognitive decline.

Lauren Gerlach:

Also, how is social engagement measured in the Nurses' Health Study? Is this a metric or questionnaire? How do they look at that? Sometimes we'll think about number of social contacts or perceived social connectedness. How do they look at it for this study?

Marcia Pescador Jimenez:

Yes, absolutely. Actually, let me go back quickly through social engagement because it was exactly about the number of contacts that you still have and the frequency of the contacts, I want to say, but I don't know if the scale has a particular name and I would love to give you that name. Is it okay if we circle back to that question?

Matt Davis:

I was just curious. I mean, it seems like the progressive adjustment is something I see a lot in epidemiology. It seems like it can provide you some insight into whether it's working the way that you think. I mean, does the association between greenspace and cognitive decline go away when you control for physical activity, social interaction, all these other types of things? Can you make it go away as proof of concept of what the mechanism might be?

Marcia Pescador Jimenez:

We actually were very interested in evaluating this potential pathways through a causal framework, so random mediation analysis, and the idea of the mediation analysis is that it would get us the percentage of the association between greenness and cognitive decline that was explained through the pathway.

So in the case of physical activity, social engagement, and air pollution, we actually saw that the percentage that was explained by these three factors was actually not significant, meaning that the confidence interval included the null, which led us to believe that maybe the mechanism, at least with cognitive decline, it's not going through there.

What was interesting was that mental health did explain about 18% of the association between greenness at midlife and cognitive function at baseline, but then it also explained about 24% of the association between greenness at midlife and cognitive decline over time. So this just speaks first of the importance of mental health as a pathway from greenness to cognitive health, but also about the importance of mental health in the risk of Alzheimer's disease and related dementias.

Lauren Gerlach:

You mentioned several times in the paper this concept of the equigenesis hypothesis of greenspace exposure. Can you tell us a little bit about what that is and why it's particularly relevant for health disparity populations?

Marcia Pescador Jimenez:

Yes, absolutely. The equigenesis hypothesis refers to the potential of greenness exposure to mitigate health inequalities. Epidemiological studies have indicated that greenness may have health effects that are especially beneficial for socioeconomically disadvantaged groups who usually have lower access to affordable alternative health-promoting resources.

In our study, our results showed that the equigenesis hypothesis of greenness held for baseline cognitive function, where we saw beneficial association of greenness for participants living in areas of low socioeconomic status, but we did not observe a beneficial association of greenness of participants living in areas of high socioeconomic status. However, when we looked at cognitive decline, we actually did not see evidence supporting the equigenesis hypothesis where participants living in areas of low socioeconomic status had a similar beneficial association from greenness compared to participants living in areas of high socioeconomic status.

Lauren Gerlach:

This may be more of a comment, but I wonder how we can get healthcare providers to think about prescribing time outside as a way to improve health and potentially prevent cognitive decline.

I know you talked a little bit about the modifiable impacts of this work. Either in work that your team's doing or thinking about some of the policy impact of this, what do you see as next steps?

Marcia Pescador Jimenez:

I think what I've enjoyed the most about this type of work is that it is a happy place for me in the sense that I go outside and I see trees. I was like, "Yes, you're helping. This is good. I should just keep going." And I've seen this across many different health outcomes, right? We talked about cardiovascular, mental health, cognitive health.

I think the one limitation that these studies have had is first of all, we are looking at greenness in isolation, whereas that's not necessarily the case. We are exposed to multiple environmental exposures at the same time. We're exposed to air pollution, noise, neighborhood deprivation. So I think that's a first next step for me, and that's actually what the R01 that was recently funded is going to look at. It's evaluating what we're calling the external exposome or interactions of key environmental factors and how are they interacting to affect cognitive health?

The other limitation that some of these studies have had, and we hinted at it too, is that these studies have been made mostly in white populations, but Black and Latino participants in particular have higher risk of Alzheimer's disease and related dementia, and they also have lower exposure to greenspace and higher exposure to air pollution, noise, heat, and that's not necessarily something that has been evaluated at its fullest. So this R01 is looking at multiple cohorts to join forces and gain statistical power to look at racial and ethnic disparities, not only in environmental exposures, but also in the association between environmental exposures with Alzheimer's disease and related dementias.

Lauren Gerlach:

Is there anything we haven't covered that you want our listeners to know?

Marcia Pescador Jimenez:

I think that the way that I like ending these type of discussions is to actually go outside and take a walk. We sit at our desks most of the time, and the science is telling us that we should spend more time outside, even for a 10-minute walk between meetings. It just gives you better focus. You can come back happier, healthier, and focus better. And also, it's good for, as I said, for the family, for your loved ones. To be in a better mood is just better overall, I would say.

Matt Davis:

I think that's our cue to wrap this up and go outside. Marcia, thank you so much for joining us.

If you enjoyed our discussion today, please consider subscribing to our podcast. Other episodes can be found on Apple Podcasts, Spotify, and SoundCloud, as well as directly from us at capra.med.umich.edu, where a full transcript of this episode is also available. On our website, you'll also find links to other resources we've created specifically for dementia research.

Music and engineering for this podcast was provided by Dan Langa. More information is available at www.danlanga.com.

Minding Memory is part of the Michigan Medicine Podcast Network. Find more shows at michiganmedicine.org/podcasts. Support for this podcast comes from the National Institute on Aging at the National Institutes of Health, as well as the Institute for Healthcare Policy and Innovation at the University of Michigan. The views expressed in this podcast do not necessarily represent the views of the NIH or the University of Michigan.

Thanks for joining us, and we'll be back soon.