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Today, we're going to be discussing her review article in the Movement Disorders Journal Subjective Cognitive Complaints in Parkinson's Disease, a Systematic Review and Meta Analysis. And the reason that we've asked her on today is because this article has won the MDJ review article of the year for 2024.
So congratulations on that. Dr. Goldman.
[00:00:57] Dr. Jennifer Goldman: Thank you so much, Sara. And we're truly [00:01:00] honored for that award and the opportunity to talk about our article on behalf of my coauthors.
[00:01:07] Dr. Sara Schaefer: Let's start with some of the language raised in your paper. There is subjective cognitive complaints, objective cognitive impairment, Parkinson's MCI, PDMCI, dementia. How do you define each of these and how are the presence of subjective cognitive complaints elucidated?
[00:01:28] Dr. Jennifer Goldman: Thanks, this is a great place to start as terminology is always such a foundational piece and we know that language and how it's used are critical, but often confusing points. So to break this down a little bit, let me go over each 1 of those aspects that you mentioned. So to start off with subjective cognitive complaints, or sometimes abbreviated SCC's.
These are essentially a person's concern about their cognition and its [00:02:00] decline in any type of cognitive domain, and it can be present with or without objective cognitive deficits on testing or rating scales. These types of subjective kind of complaints are typically reported by the patient themselves, but as we know, they've also been incorporated into a number of diagnostic criteria, such as for PDMCI which we'll get to in a moment, and could also be noted by a caregiver or clinician.
Objective cognitive impairment refers to the presence of impaired performance on cognitive tests or another way to be able to demonstrate a measurable change in someone's cognition. Often, these are tests that address global aspects of cognition, or even specific areas like attention, executive function, memory, et cetera, and compared to scores developed by [00:03:00] normative values based on someone's age, gender, education, and so forth, demonstrate some sort of objective change. They can also be compared to that particular person's prior performance or other ways that denote that they fall below a certain range of what we consider normal or healthy cognition.
Now, PDMCI, or Parkinson's mild cognitive impairment that you mentioned, refers to the occurrence of cognitive deficits in the context of Parkinson's that can be reported either by the patient or the informant or observed by the clinician.
Generally in MCI, such as in PDMCI, these cognitive deficits are not sufficient enough to interfere significantly with functional independence or everyday activities. And in 2012, the MDS published a criteria for PDMCI [00:04:00] that showed that either these cognitive deficits could be demonstrated with formal neuropsychological test batteries, more limited test batteries, or a scale of global cognitive abilities.
Now, lastly, dementia refers to a cognitive syndrome in which more than 1 cognitive area or domain is affected. And to a substantial degree that it affects everyday activities. So, for example, in Parkinson's one can note that dementia could include more than 1 cognitive domain does not need to include memory impairment, but it could include areas like executive function or visual spatial function, which may be more prominent in Parkinson's.
So, as far as elucidating the presence of subjective cognitive complaints, we can do this in a number of ways. And this is actually important topic, because how items of interest are [00:05:00] measured. Can affect various research studies and their findings. So, for example, we can subjective cognitive complaints from the self report of the patient through various interview questions.
We can also do this through different types of questionnaires. And some of these questionnaires may ask general or global questions, like, do you feel like you have a change in your memory? Or do you feel like your memory declined? Or they can get more specific, such as asking, do you forget appointments?
Do you forget medications? Do you get lost when navigating around or other areas like that? Right now, there isn't a good consensus on how we address or assess the subjective cognitive complaints in Parkinson's, but hopefully that that gives an outline of all these different terminologies and where they fall in a spectrum of cognitive impairment in Parkinson's.
[00:05:59] Dr. Sara Schaefer: Yeah, it's really [00:06:00] helpful for me to have an overview of that language and make sure we're all talking about the same thing or, when we use certain words so you mentioned that in your paper that there's considerable overlap in Parkinson's patients between all of these cognitive issues, and they're kind of on this continuum, right, and people can have only subjective or subjective and objective findings, and you also mentioned overlap with neuropsychiatric symptoms such as anxiety and depression. Can you explain what was known about all the relationships between one another in this population prior to your work.
[00:06:38] Dr. Jennifer Goldman: Sure. So prior to our study the presence of subjective cognitive complaints has been recognized throughout a number of years, but the literature has been really quite variable as suggested by ranges that can be estimated about 15 to all the way up to 80 percent and [00:07:00] that depends a little bit on.
The study population, the measures used, and potentially the incorporation of objective cognitive impairment, or even neuropsychiatric symptoms, like the ones you mentioned. So we do know that cognition and neuropsychiatric symptoms like depression, anxiety, apathy and others can be highly interconnected and interrelated in Parkinson's themselves.
And in terms of thinking about this with subjective cognitive complaints, that literature has been also quite variable with studies reporting different degrees of association of the neuropsychiatric symptoms with subjective cognitive complaints, some stronger evidence and some weaker associations.
Interestingly, in some studies, the association between the neuropsychiatric symptoms and the subjective cognitive complaints was found, [00:08:00] even in those studies that excluded patients who had clinically relevant psychiatric disorders, like major depressive disorder. And in other studies, with this relationship, sometimes treating the symptoms of depression or anxiety could improve aspects of cognitive function and Parkinson's and in those studies that had follow up of people diagnosed with PDMCI might even show that t his type of treatment could revert the PDMCI to normal cognition at follow up visits and assessments. So, all in all, this highlights really how interconnected cognitive and behavioral aspects of Parkinson's can be.
[00:08:44] Dr. Sara Schaefer: Yeah, well, no surprises there for sure. I mean, we've all heard about pseudo dementia in the setting of really profound depression, for example. And as somebody who sees a lot of general neurology, I'm sure anybody who sees that population will know [00:09:00] that cognitive complaints are extraordinarily common in patients with neurobehavioral and psychiatric disease.
What did you hope to add to the literature with your study and how did you conduct it?
[00:09:11] Dr. Jennifer Goldman: We were interested in a number of important aspects of subjective cognitive complaints and Parkinson's and also going back to the point you just made. We know there's a strong relationship many times across these neuropsychiatric symptoms with cognition and mood and behavior, but we often think about them in their own silos and their own vacuums, which is not really how.
It all it all plays out as we know. So the aspect we wanted to address was to determine the prevalence rate of subjective cognitive complaints in Parkinson's across the published literature. And to understand what different factors might help explain this variability that we've seen in the [00:10:00] literature that I mentioned before.
And 2nd, we were interested in examining the associations between these subjective cognitive complaints in Parkinson's and different features, like objective testing. And neuropsychiatric symptoms, and whether they had any predictive value of people who would go on to develop mild cognitive impairment or dementia.
And so, in order to conduct this study. We conducted a systematic review and meta analysis with specific methodology, outlining our criteria for including and excluding different types of articles, and then of course, assessing the articles, quality, their bias and heterogeneity plus the strengths of the associations that I just mentioned.
So we focused on studies of adults with Parkinson's that looked at the [00:11:00] frequency of subjective cognitive complaints, their cross sectional or longitudinal associations with cognitive changes on objective testing and focused on those that were in the English language.
When we looked at these studies, we analyze the data to ascertain the prevalence rates to look at the different moderators that might influence these frequency rates and the associations with the variables of interest to us, like those neuropsychiatric symptoms and affect sizes of these.
And so when we did our search, we found 204 articles. Of which using our inclusion and exclusion criteria determined before the study reviewed 138 and then from those, we included 31 in our final analyses.
[00:11:52] Dr. Sara Schaefer: And what did you find?
[00:11:54] Dr. Jennifer Goldman: So our, our main findings were that in compiling all these studies, [00:12:00] there was a pooled prevalence of subjective cognitive complaints in Parkinson's of 36%. We found that there were certain variables such as female sex, staging of Parkinson's, levodopa equivalent doses exclusion of patients with objective cognitive impairment and certain types of measurement instruments that influence these frequencies.
That is, we found higher prevalences of subjective cognitive complaints in those studies that had greater numbers of females in their cohorts patients with lower Hoehn and Yahr stages or lower levodopa equivalence. we excluded those with objective cognitive impairments, and those that we're using global measures of subjective cognitive complaints compared to very specific examples of cognitive changes or mixed instruments.
Interestingly, [00:13:00] there were some other aspects that we did not find to affect the prevalence rates, and these included factors such as age, education, age at disease onset or disease duration, motor scores, or whether actually the patients were treated with Parkinson's medications or were de novo. We also found that in terms of predictive values for the presence of subjective cognitive complaints with objective cognitive decline, several studies revealed that cognitively healthy patients who expressed subjective cognitive Complaints had a greater risk more than two times to progress to objective cognitive decline, such as PDMCI or dementia in follow up.
[00:13:48] Dr. Sara Schaefer: You mentioned the female male discrepancy that you found higher rates of subjective cognitive complaints, the more females were involved in the studies. Can you [00:14:00] talk about what you made of that finding?
[00:14:03] Dr. Jennifer Goldman: Yes, that's a really interesting finding and the differences between males and females in PD and cognition likely needs further attention and study to understand. The frequency and factors that influence these changes, but a few thoughts as to explain why we may have seen the greater association in females could be a number of factors.
So, different levels of awareness of one's own cognition, one's own. Body or what's happening within the disease. There's a close relationship with the neuropsychiatric symptoms that we mentioned, and several of these may be more common in women than men, such as depression or anxiety. And there may be potentially biological factors related to hormone levels, estrogen levels, or changes that [00:15:00] happen in women over the lifespan that could contribute. So some of these influences may not be PD or Parkinson's specific, but may relate to other biological and hormonal factors.
[00:15:15] Dr. Sara Schaefer: So that raises a question. I'm throwing you a bit of a curveball here. You are a cognitive and behavioral neurologist trained in addition to being movement disorders, correct? And I was wondering after reading about the hormonal influences, if that has panned out in other populations in the literature.
[00:15:33] Dr. Jennifer Goldman: Yeah, it's
such an intriguing area and In other neurologic disorders, such as Alzheimer's, as you may be aware, there have been associations between female sex and cognitive impairment. There's a lot more to be learned about. Even the relationship of estrogen and dopamine and in Parkinson's specifically.
And then, of course, where [00:16:00] there are changes throughout the lifespan of females, there may be hormonal fluctuations that could affect cognition at certain time points as well.
[00:16:10] Dr. Sara Schaefer: Was there anything you gleaned from the pattern of cognitive performance measures and their relationship with SCCs.
[00:16:19] Dr. Jennifer Goldman: This is also an interesting area because, as we know, cognition is such a complex and broad entity unto itself, and sometimes people tend to equate cognition and cognitive changes with changes in memory. But as we know, in Parkinson's, there can be many different areas affected, including attention, working memory, executive function, and so forth.
So it's really important to try to dissect some of these cognitive changes apart from just global cognition. So we did find that the subjective cognitive complaints were significantly, albeit weakly, [00:17:00] associated with objective changes on cognitive domains, including executive function, attention, working memory and memory, but not so much with language or visual spatial abilities.
And I think this is intriguing as well, because these. Areas that I just mentioned, executive function attention into some degree of memory correspond more to that frontal striatal pathways that we see in Parkinson's often affected earlier in contrast to some of the more posterior cortical deficits associated with language and visual spatial changes.
It's not clear exactly what this represents, but we also found that some of these findings might reflect differences in how the cognitive domains or cognition is measured. So, different types of instruments, different cognitive tests possibly at the [00:18:00] stage at which they're reporting people might be more focused on some of these areas like executive function or attention and memory that also tend to be more prominent in Parkinson's.
[00:18:11] Dr. Sara Schaefer: Another detail that I wanted to ask you about, you mentioned that there were similar percentages of. SCCs reported in high and low education populations. With very high baseline education patients, I've always thought that they may. Notice subjective cognitive concerns well, before the objective cognitive impairment manifest due to being able to compensate more for some time, like, they're having self perceived problems before the MOCA score starts to drop, for example, and, I may therefore be less reassured by a normal score in patients who have very high levels of education. What do you think about these results and that kind of thought process clinically?[00:19:00]
[00:19:00] Dr. Jennifer Goldman: I agree that this is an interesting finding. And to some element reframes what we've always been taught or thinking about the effects or protective effects of high levels of education. So it definitely is an interesting area to look at further in terms of education levels. So I do think it's worth a quick note that.
In many of the studies, however, that were included, they did have relatively high levels of education. The minority of the studies were low levels of education with that said. You know, the change for an individual, a particular person, and how they notice it often in terms of their function, their cognitive resilience, how they get around, as you mentioned, remains an [00:20:00] essential area that we need to address regardless of education.
So, some of it is, testing on test performance. But really a center of the issue is one's perception of experiencing cognitive change and what it means to them in terms of function and functional cognition.
[00:20:22] Dr. Sara Schaefer: Given that your study did include both people with and without objective cognitive impairment. I was wondering if, patients with only subjective, but not objective cognitive impairment. If it would still be similar percentages in those 2 populations, if you took out those who also had objective findings,
[00:20:43] Dr. Jennifer Goldman: Yes, and so I think what we found is that the lack of patient reported subjective cognitive complaints cannot fully or solely be used to inform how someone performs on an objective [00:21:00] neuropsychological assessment and really they both represent important aspects that we need to consider separately, but also collectively.
And I think this will be even more important when we start to think about how do we incorporate them in diagnosing someone with PDMCI or tracking change over time for decline?
[00:21:24] Dr. Sara Schaefer: Well, that segues really nicely into my next question, which was about the finding that. There's actually a bit of an inverse association between an objective cognitive impairment and subjective cognitive impairment. And you talked about a couple of reasons that could be including as a disease progresses and an objective cognitive impairment becomes more pronounced, maybe the patients have more anosognosia to their, Cognitive difficulties, or maybe the motor symptoms and other non motor symptoms are more pronounced and they're focused more on those. I wonder if [00:22:00] you think your data included only patient reported and not care partner reported impressions of subjective cognitive complaints. Do you think the data would be different if you also included care partners?
[00:22:13] Dr. Jennifer Goldman: Thanks so much for this this question, because We only included that the patient studies and information from an informant or care partner is also valuable in its own way. And there's literature that exists that shows that there can be differing opinions of cognition and cognitive performance between patients and their care partners actually going in both directions of who thinks there might be impairment or changes.
And so, while it's not always captured in the measurement tools used, it becomes an important next level question to ask in terms of getting an informants opinion and in working [00:23:00] with any cognitively impaired population Parkinson's or otherwise getting that information from someone who knows the patient is also a piece of the interview and medical history.
When we see the lower rates of reporting the subjective cognitive complaints, we may see that when people have more advanced cognitive challenges or lose insight into their abilities, but I think it's also important to recognize they might be doing fewer activities in the setting of PD progression that might influence a day to day activities or functional changes and also not to neglect that. Their ability to communicate these changes that they experience may change over time with their Parkinson's itself.
[00:23:50] Dr. Sara Schaefer: Sounds like the long and short of it is really that you need to get data from a lot of different angles because although there may be correlations, things can be [00:24:00] independent of each other in terms of what the patient reports, what the care partner reports the objective findings at the end of the day. All of us as clinical providers have patients coming in every day who talk about subjective cognitive complaints. What should a clinical provider do when a Parkinson's patient is sitting in front of them and endorsing these subjective concerns?
[00:24:25] Dr. Jennifer Goldman: I think the 1st thing a clinical provider should do is to acknowledge this person's concerns and take their. Subjective cognitive complaints or endorsement of cognitive or any other changes seriously. I think the presence of subjective cognitive complaints should lead us to investigate further and that could be with cognitive mood or behavioral screening asking what I call next level questions to [00:25:00] understand what this change means for that individual.
How do they notice it? When do they notice it? What does this mean in terms of function and day to day activities? And then really, what are the tools that we can use to to measure this? And knowing that many times people have very busy clinics and limited time who else might be able to assist in assessing the cognition or behavioral aspects.
And that could be our. Neuropsychologist or psychologist or occupational therapist, speech language pathologist, many people can play a role in assessing someone's cognition and so forth. The other piece that one should think about is in terms of having a baseline for neuropsychological assessments.
We are often very, very good at establishing motor baselines for patients with Parkinson's, but not as [00:26:00] good or robust getting screens or baselines for cognitive, neuropsychiatric, or other non motor symptoms. And so having a baseline can tell us where someone's at, at that period of time, and then follow them over time with the assessments to detect any changes.
[00:26:18] Dr. Sara Schaefer: And what do you see as the future directions for this line of work?
[00:26:24] Dr. Jennifer Goldman: Thank you in terms of the future directions. I think what we've found from the systematic review and meta analysis is that there is an opportunity to better understand the presence, the frequency and characteristics and predictive nature of subjective cognitive complaints in Parkinson's. Our work also highlights that there's a need for recommendations and a need for consensus on how we should best define and classify these subjective [00:27:00] cognitive complaints and to address different ways that we can incorporate them in both clinical care and research studies. I think ultimately. Early identification and knowing that someone has subjective cognitive complaints and what they might mean could lead us to early interventions.
Ultimately therapies that can prevent or slow down cognitive decline. But also in the interim, what sorts of aspects we could control, which might include things like lifestyle modifications, the role of exercise, diet, sleep, assessing hearing and, and so forth. So to start to appreciate the subjective cognitive complaints in people with Parkinson's.
[00:27:49] Dr. Sara Schaefer: Thank you very much for this stimulating conversation. Very interesting work and congratulations again on your award for the Movement Disorders Journal [00:28:00] Review article of the year.
[00:28:02] Dr. Jennifer Goldman: Thank you so much. It's been a pleasure speaking with you.