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Okay, some directions for future research here. We are interested in looking at how fibromyalgia patients perform when they are distracted. We call this “dividing attention” where they have to do two things at once. And we think given their more apparent limited working memory capacity that they may have particular problems with tasks that require them to switch back and forth, or that require them to perform multiple tasks at the same time. We also think that they may not, like older adults, they may remember the gist or the target information that they’ve learned but they are going to have a lot of trouble remembering the context in which they learned the information. In other words, they will remember that something is true but they won’t remember where they read it or who they heard it from. We call that “source memory”. Finally, we are very very interested in doing some functional neuro-imaging of these patients. In functional neuro-imaging you have patients in an MRI scanner and you collect data from the patients performing cognitive tasks while they are in the scanner and you get images of their brain and what parts of the brain are activated by measuring cerebral blood flow and compare that to baseline tests that are less cognitively demanding. And here’s an interesting pattern of results that I’d like to propose might be typical of FM patients. If you look at the superior cortex – this is a superior view – you can see that there is a lot of cortical activation on both the left and the right sides of the older adults on a verbal working memory test. But for the younger adults, the activation is primarily left frontal. There is much more left activation in the young adults and it’s bilateral in the older adults. Here you can see a lot of left activation in the young adults and a lot of left activation in the old adults. Here there is almost no activation in the right cortex in the young adults but there is a great deal of right frontal activation in the older adults.
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But here’s the point. Older adults are recruiting more cortex bilaterally to perform tasks than young adults are. And the young adults are using primarily left cortex. And it’s occurred to us that we may find that the FM patients who are reporting these cognitive impairments, when they are placed in a MRI scanner, may actually recruit different areas of the brain or more brain tissue to perform the same tasks as their age-matched controls and look like old adults neuro-biologically. Or alternatively, they perform very much like young adults neuro-biologically and their poor performance may be attributed to other reasons. So these are interesting and exciting questions and I think we are on the verge of being able to get a window into not only the nature of the memory problems but also possibly some of the underpinnings of what causes the cognitive problems that fibromyalgia patients report.
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What about memory complaints? We use the Pincus Cognitive Symptoms Inventory, which is simply ask patients what they complain about with respect to their memory. What are their problems? We also have a longer more elaborate cognitive inventory called the Meta-Memory Scale that I’m not going to go into here, that will give us an even better handle on the memory complaints of fibromyalgia patients. But here’s what’s interesting, I think, of the memory complaints of fibromyalgia patients. The fibromyalgia patients report that their memory is worse than the older adults, you can see that they have more memory complaints than the older adults yet they are performing like the older adults. Now one could take this as a symptom of whining, but think about it. Think about the fact that you are a 30-year-old and your memory is performing like a 50-year-old. It makes sense that people … their memory is not age-appropriate and even though the older adults complain more about their memory than the young adults – as they should, because their memory actually is worse. Complaint is the wrong word. They self-report more problems with memory, the old adults do, and they do have more problems with memory. The fibromyalgia patients are self-reporting even more problems than the old adults, but that makes sense to me because their memory problems are not age-appropriate and they are very unusual for people and out of range for people in their age group.

So what can we conclude? I think we can conclude first that fibromyalgia patients show normal speed of processing, similar to age-matched controls and that’s a very important finding. I think the finding that they are like the age-matched controls in some ways has a lot of credibility and potential for interpreting the differences where they are not like the age-matched controls. The FM patients perform significantly worse than age-matched controls and very much like older adults on measures of working memory, verbal fluency and long-term memory. Quite interestingly, they perform more poorly on vocabulary tests than carefully matched age controls and more poorly than older adults. In addition, to sort of provide you with a broader window on the meaning of these findings, FM patients in general show problems with cognitive tasks that are primarily controlled by prefrontal cortex. This vocabulary deficit appears to be unique to the FM patients and is not typical, as I mentioned, of either old or young adults. And as I mentioned, they have greater memory complaints than the elderly despite similar memory performance to the elderly.

Verbal fluency, also another highly frontal task in terms of cortex. This is, to remind you, where subjects are given a letter like F and told to produce as many words as they can think of that begin with the letter F. They had three tasks like this and you can see again that very much like older adults FM patients performed more poorly than age-matched controls.
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Finally, recognition is a more passive test that doesn’t engage the central executive dorsal lateral frontal cortex and it’s more hippocampal and passive in nature. Here you can see – just to remind you, subjects are given lists of words to study and then they are given another list, some of which with the words they’ve studied and some of which are what we call “lures” or “false alarmed” words. And they have to say if they saw that word before. No one shows any deficits on this test. The older adults, there’s no active retrieval required here. The older adults do fine. As to the fibromyalgia patients, no one is performing at ceiling. So it’s not that they are getting everything correct. This is a sensitive task but all the groups are performing the same on it.
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Finally, this is a puzzling finding. You’ll recall that I showed that across the life span vocabulary scores remain intact. That was about the one set of lines that were level or actually went up a little bit with age. Interestingly, the fibromyalgia patients performed more poorly on the vocabulary tasks than either the older controls or the age-matched controls. And I was sufficiently surprised by this finding that I thought there must be something wrong with our sampling. I just wanted to show you – I don’t know if you can see this – how carefully matched these subjects are. That they are absolutely precisely matched, not only in terms of age but also in terms of years of education. So these are the 20 subjects and each young control and old control was very precisely matched, so I cannot find any basis for interpreting the poor vocabulary of the fibromyalgia patients as being due to some kind of artifact of our sampling. These patients will spontaneously report that they have a lot of word finding difficulties, that they have trouble using vocabulary. So this may square with some of your clinical experiences.

Now I’d like to turn to the data on cognitive function. The first data that I am going to show you is this speed of processing task. As I mentioned to you, we see speed of processing as fundamental to all of cognition. We take it as almost an overall measure of neuronal integrity, or sort of general neurologic intact-ness. It’s a very simple task. In this particular task subjects are given columns and columns of these items and they are just told to say if these items same or different. On the number of items that they can … it’s a simple perceptual scanning task. The number of items that they can complete in tow minutes is the measure of their speed of processing. This is an incredibly reliable powerful measure. If I could know only one thing about a person and if I could be only one thing cognitively I would pick being fast. Because it controls so much other variants in cognition. So how do the fibromyalgia patients look? This is very interesting. You can see that the older controls are only 20 years older than the fibromyalgia patients, score reliably lower than the age-matched controls and that the FM patients look exactly like the age-matched controls. So the fibromyalgia patients, this overall measure that I’m saying is an overall measure of intact-ness or neuronal integrity, the fibromyalgia patients look exactly like their age-matched controls. So their speed of processing is intact and I feel very confident about this because we had three different speed tasks in our battery. They are highly reliable tasks.
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So the next task we gave subjects was a working memory task and we see working memory as sort of the horsepower, the mental horsepower, mental energy you bring to a cognitive situation. It’s sort of your online processing power. This is an example of the working memory test. The subjects will say, the experimentalist will say, “The fans at the football game wore hats and scarves” and then a question will flash up on the screen – the subjects are working at a computer – “Where are the fans?” Well, you know, the answer is “They are at the football game” so they’ll pick A. At the same time they have to remember the last word in the sentence. Then another sentence will be read and a question about it will flash up and they’ll answer it and they’ll have to remember the last word in the sentence. So now their load is “scarves and city”. Then recall will come up on the screen and they have to answer “scarves and city” and they might see as many … some subjects can get as many as eight or nine of these in a row correct. In other words, they can answer eight questions in a row and retain the eight last items in the sentence without error. How ever many they can get correct like that is … it goes up one by one. It’s their working memory capacity and we have three measures of that. As you can see that when we looked at their working memory capacity, which again is utterly central to all of cognition, we do find that the FM patients look exactly like the elderly and they perform significantly worse than the age-matched controls, suggesting some deficit in what we would call this processing resource, or central executive function.
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Here we have long-term memory. In this case subjects were given lists of words. They were given 16 words and they were asked to recall as many words as they can. The number of words recalled far exceeds 16 because this was summed across three lists. Here you can again see that very much like the working memory measures, the FM patients look like older adult controls and are performing along with the older controls significantly worse than the age-matched controls.

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This is what performance on these tests look like. Across, a sample of older, of adults age 20-90. And you can see that performance, regrettably for all of us in this room, begins declining in your 20’s and all the tasks – speed of processing, working memory, long-term memory – it doesn’t seem to matter whether the tasks are visual, spatial or verbal, they only task that seems to be protected from age is, as I mentioned, is world knowledge. Those are three measures of vocabulary. This data represents 350 subjects, 50 at each decade. These are all healthy, normal adults drawn from the community. So basically we are looking at two decade age differences. In other words, does fibromyalgia move patients two decades further along on this graph from their actual chronological age? So that’s sort of a little bit about the logic of the study.
As I mentioned, we have measures of sleep disturbance, depression, pain, fatigue anxiety. Beliefs about memory and there is some evidence that people’s memory functions differently when they are tested at their preferred time of day. Like if you are a morning person and you are tested in the evening, your memory will be worse. So we also looked at preferred time of day. But all of these patients were tested in the afternoon because of the salivary cortisol samples and the plasma cortisol.
Okay, what do our participants look like? The median age of the fibromyalgia patients was 47. You can see the older controls are exactly 20 years older and the age-matched controls are within a year of the age of the fibromyalgia patients. These are well-educated participants. The fibromyalgia patients score higher on the geriatric depression scale as well as the Beck Depression Inventory. I’ll make a comment about that in a moment. And they also report having more pain than the older adults and the age-matched controls. Graphically here’s the depression. We have two measures of depression. The point I want to make is that on the Beck Depression Inventory, mild depression is 19 and our patient’s score mean is 16 and on the GDS mild depression is 15 and our patients are at about a 12. So that even though they are significantly more depressed in a sense than the older controls and the age-matched controls, none of our subjects even meet the criteria for mild depression according to these well-known instruments.
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In terms of pain, you can see that our patients, the FM patients, report more pain on two different measures: the Ames II and the McGill Pain Inventory compared to older controls and age-matched controls. We also have some chronic fatigue subjects that I didn’t include here because we only had 10 and it seemed an inadequate number. But the FM’s reliably report more pain and the chronic fatigues as well. Sleep quality: the FM patients and the older adults sleep somewhat more poorly than age-matched controls. So that’s sort of the background variables that you should keep in mind as we look at the cognitive function of these patients.

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The study I’m going to talk about today … I’m going to try to give you a quick overview of the research protocol, because I’d really like to focus on the data. We had 20 FM patients, and you need to think of these patients as existing in triplets. For instance the triplets being and age-match. For each FM patient we had an age-matched control. In other words, another individual without FM that was exactly the same age and education as the FM patient. And then we had an older adult that was of the same level of education but was 20-years older than the individual FM patient, plus or minus two years. So the patients are all very carefully matched to an age-matched control and an elderly control.

A little bit about our FM patients. They meet the 1990 ACR criteria for fibromyalgia. They were actively screened and do not have active depression, all the subjects who participated in this study. All drugs except SSRI’s for 14 days. So these are subjects who are free from drugs that are participating in this study. And they don’t have any other complicating rheumatological conditions besides fibromyalgia. Some of the things that we measured, besides cognitive function, we measured sleep quality by giving them activity monitors that they strapped on their wrists. They are very sensitive measures of sleep quality because they measure sleep movement and seem to predict pretty carefully how much waking and movement occurred in the individuals sleep. We also have paper and pencil measures of depression, anxiety, time of day preference, their beliefs about their own memory. In other words, what are the fibromyalgia patient’s memory complaints? How severely to they rate their pain and how fatigued they are. These are all self-report data. We gave them three blocks of cognitive tests over a two hour period. We also measured salivary cortisol during testing repeatedly. And we also measured plasma cortisol and ACTH after testing. But primarily I’m going to talk about the cognitive measures today, given the complexity of the project and the amount of time available. But basically, five days before subjects came in for testing they wore the Actigraph, the sleep monitor, so that we would know what their sleep quality was for five days prior to testing. When they came into the lab we would take saliva samples at the times indicated. All subjects were tested in the afternoon, and then they were given the questionnaires in terms of anxiety, depression, that type of thing. Then we had three blocks of cognitive testing. And basically they got three versions of the same task across these blocks, and the reason for that will be clear in a moment.
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