MJA receives research support from ARHQ (K08HS24159), a 1Florida ADRC pilot grant (AG047266), the Florida Department of Health Ed & Ethel Moore research program, and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. AT is employed by the Lewy Body Dementia Association. BP receives research support from an American Academy of Neurology Clinical Research Training Scholarship in Lewy Body Dementia and received compensation for consultation with Medtronic. GS receives research support from the 1Florida ADRC (AG047266) and the Florida Department of Health Ed & Ethel Moore research program. NG, SA, TM, and AMK have no competing interests to report. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Funding bodies are placing increased emphasis on patient and public involvement in research, but the research priorities of individuals and caregivers living with dementia with Lewy bodies (DLB) are unknown.
Investigators conducted telephone interviews with individuals living with DLB and caregivers. Participants were recruited from a Lewy Body Dementia Association Research Center of Excellence. Interviews employed a semi-structured questionnaire querying research needs in different categories and then asking participants to select their top priorities. Investigators used a qualitative descriptive approach to analyze transcripts and identify themes.
Twenty individuals with DLB and 25 caregivers participated. Seventeen from each group participated as part of a patient-caregiver dyad. Twenty-three of the caregivers were spouses, two were daughters. Individuals with DLB and caregivers identified research needs relating to focusing on awareness, determining the cause of DLB, improving diagnosis, and investigating what to expect/disease stages. Participants also highlighted DLB symptoms needing additional research, therapies to prevent, cure, or slow the progression of DLB, and research targeting daily function and quality of life, caregiving, and improving education.
These findings support the research priorities defined in the National Institutes of Health dementia care summits in addition to ADRD priority-setting summits. Research is needed across all domains of DLB. Funding should be informed by the priorities of all relevant stakeholders and support research investigating causes, natural history, biomarkers, and treatment in addition to research targeting themes regarding living with disease (e.g. independence, quality of life, caregiving, and education).
Funding bodies including the National Institutes of Health (NIH) are placing increased emphasis on patient and public involvement in research. Patients can have a role throughout the research process, from study design to dissemination [
The Advisory Council on Alzheimer’s Research, Care and Services recommends that all funders “should establish the engagement of the AD/ADRD [Alzheimer disease/ Alzheimer-disease related dementia] community as a standard practice in… participating in setting national research priorities for AD/ADRD…” [
Involvement of patient representatives alongside experts in priority setting reflects a “participation” engagement strategy. Through participation, representatives have an active and equal voice in the process. Participation strategies usually rely on small numbers of representatives, potentially missing other perspectives. Consultation strategies (e.g. surveys, interviews, focus groups) collect a variety of views from larger groups of people, but fail to give patient representatives an active voice in the process. Employing participation and consultation approaches as complementary may be the optimal approach to incorporate the views of a diverse group while also giving patient representatives an equal and active voice in decision making [
Stakeholders representing individuals with Lewy body dementia participated in NIH AD/ADRD priority setting [
The study used telephone interviews to investigate the research priorities of individuals living with DLB and caregivers of individuals living with DLB. Investigators used a qualitative descriptive approach [
Individuals with DLB and caregivers of individuals with DLB were recruited from the UF Health Norman Fixel Institute for Neurological Diseases, a Lewy Body Dementia Association Research Center of Excellence. Inclusion criteria were: (1) patient or caregiver of a patient followed at the Fixel Institute, (2) personal diagnosis of DLB [
The PI (MJA), a DLB specialist, drafted the semi-structured interview guide (
A research assistant with qualitative research experience conducted the telephone interviews (SA). The research assistant had no relationship with participants prior to the study. Interviews occurred via telephone to allow individuals to participate from home. Participants selected the interview times. The preferred approach was to interview individuals with DLB and their caregivers separately (if both participated), but the interviewer accommodated requests for the caregiver to be present during the patient interview. Any caregiver opinions offered during a patient interview were coded as belonging to the caregiver, not the individual with DLB. Audio recording started after allowing for participant questions and verbal consent at the beginning of the call. A professional service transcribed the interviews verbatim, so member checking was not performed.
Investigators used tables in Microsoft Word® and Excel 2016® to organize data and a qualitative descriptive approach to identify and organize themes [
Interviews occurred between 1/22/2018 and 5/6/2019. Twenty individuals with DLB and 25 caregivers participated (
Individuals with dementia with Lewy bodies (n = 20) | Caregivers of individuals with dementia with Lewy bodies (n = 25) | |
---|---|---|
Gender (number, % male) | 18 (90%) | 3 (12%) |
Age range (number, %) | ||
50–59 | 1 (5%) | 8 (32%) |
60–69 | 10 (50%) | 9 (36%) |
70–79 | 7 (35%) | 6 (24%) |
>80 | 2 (10%) | 2 (8%) |
Race/Ethnicity | ||
White non-Hispanic | 17 (85%) | 23 (92%) |
White Hispanic | 1 (5%) | 0 (0%) |
Black | 2 (10%) | 2 (8%) |
Highest education | ||
Did not finish high school | 1 (5%) | 1 (4%) |
High school graduate (or equivalent) | 1 (5%) | 1 (4%) |
Associate degree or vocational training | 2 (10%) | 5 (20%) |
Some college, no degree | 3 (15%) | 4 (16%) |
Bachelor degree | 5 (25%) | 12 (48%) |
Advanced degree (e.g. MS, MD, PhD) | 8 (40%) | 2 (8%) |
Relationship of caregiver to individual with dementia with Lewy bodies | ||
Spouse | 23 (92%) | |
Child | 2 (8%) |
Average interview duration was 28:11 minutes for individuals with DLB and 37:10 minutes for caregivers. Caregivers helped individuals with DLB participate in two interviews. Participants confirmed that all aspects of DLB need research. Specific categories of research included focusing on awareness, determining the cause, improving diagnosis, investigating what to expect (i.e. natural history) and disease stages, DLB symptoms needing additional research, the need for therapies to prevent, cure, or slow DLB, daily function, daily life, and quality of life, caregiving, and improving education (
Key research-related themes identified in interviews with individuals with dementia with Lewy bodies and caregivers are presented in the top row of boxes. Key subthemes relating to identified themes are presented underneath the relevant research themes.
Multiple caregivers described a desire to see research focus more on increasing awareness of DLB:
(CG8, wife)
One individual with DLB and approximately half of caregivers discussed the need for more research on the cause of Lewy body disease:
(P4)
(CG21, daughter)
In addition to desiring to know causes in general, multiple participants wanted further research regarding whether other health problems, prior injuries (e.g. head trauma), exposures (e.g. from mining), a history of shift work, or a traumatic event could contribute to developing DLB.
Multiple individuals with DLB and almost half of caregivers discussed the importance of research to improve early diagnosis (
(P28)
(CG22, husband)
Theme | Exemplar Quotes |
---|---|
Improving earlier diagnosis | Of course, and the earlier—the earlier it could be, noticed, the symptoms noticed and diagnosed, I think it would be the—certainly to the patient’s advantage, as well as the researcher, the physician involved. (P16) |
If it could be diagnosed earlier, yes, it would—I mean, it would help. (CG23, wife) | |
Recognizing signs | Maybe there oughta be a way research can—I don’t know if they can do it chemically or what, but, if it could get the telltale signs so even at your regular physician that you go to day to day to day could pick up on it. (P4) |
To determine what causes it and how to recognize those signs. I mean, I have read a lot now. I didn’t initially recognize the signs. (CG2, daughter) | |
Distinguishing DLB from similar conditions | More research into the diagnosis and being able to state that that’s what somebody truly has. I know there’s no diagnostic test and all of that upfront, but better definitions so people leave with saying, “Yeah, that’s what it is. I can throw myself into this now.” (CG13, wife) |
How it’s associated with Parkinson’s and—because there’s so many things that are similar that started out as a Lewy body and then when you get a Parkinson’s diagnosis, you’re thinking, “Okay, well it was Parkinson’s. He has no dementia.” Then, when it’s flipped around, and it started with dementia, with parkinsonism, I think trying to get that more research in that to try to grasp that and what the stages and how they’re similar. (CG12, wife) | |
More about the disease itself—and diseases related to it. How it’s different from… different as a separate entity of dementia. (CG14, wife) | |
Developing diagnostic markers and testing | So from the start, I think it would be very nice if somebody who’s at the early stages of presenting symptoms like I was a few years ago, could be subjected to some kind of imaging, technology that would be able to diagnose that immediately and determine, you know, how advanced the disease is. (P28) |
I wish there’s some way that you could take something from Lewy body people, in, I don’t know, blood, or whatever, and see what the heck’s goin’ on in their brain. I know that you really can’t get a diagnosis unless—until you have an autopsy done. Well, if that’s true, then I think it should be researched somehow that maybe x-rays or MRIs or, you know, what—PET scans, you know, I don’t know, could identify it in a better—you know, how are we sure that’s really what he has? (CG4, wife) |
Multiple individuals with DLB and caregivers described needing more research to help individuals with DLB, caregivers, and healthcare professionals recognize the signs of DLB (
A common theme amongst both individuals with DLB and caregivers was the need for research into what to expect with DLB progression:
(P18)
(CG7, wife)
In addition to desiring information on what to expect with disease progression in general, multiple participants described wanting research to identify stages of DLB.
(P20)
(CG15, wife)
Participants highlighted the need for more research for many of the core and supportive features of DLB (
Core Feature | Exemplar Quotes |
---|---|
Dementia/cognitive decline | Short term memory loss. That’s the big one. (P9) |
His memory. His mind. It’s what bothers him the most, I think. He owned his own business, and he was a real whiz at figures… And he can hardly add anything now together. His addition is bad. His subtraction is bad. Just his, it’s his mind. The dementia part—is what I really notice the most. (CG16, wife) | |
Fluctuations | I don’t understand why some days I’m just so bad, and I don’t remember people and stuff, and then other days I’m just—I seem alright to me. I seem just fine and other people said, “Man I wouldn’t even know you have that disease.” (P8) |
But his primary symptom that’s very distressing to him is…cycles through some kind of shutdown and then he’s wide awake and then—it’s not sleeping. He’s not asleep. He’s awake. His eyes are wide open, but he cycles through this and it’s distressing to him. He’s gasping for air and he is totally helpless during this time period. That is the most distressing thing that has been going on for the past five years. Independent of dose, frequency, dosage form, additional medication, all of this, some inherent cycling through something that are causing physical symptoms… (CG13, wife) | |
Visual hallucinations | Well, for one thing, the people at night, hallucinations… if anything was to get me down at this point, it would be that. It’s just—I can believe it because everybody tells me, you know, that’s the way it is. But when I—when I see it, it overrides what the people tells me. (P11) |
Well, right now, of course, it’s the hallucinations and the way he looks and sees things. The hallucinations are terrible for him. (CG15, wife) | |
REM sleep behavior disorder | The REM sleep disorder. Because that’s one of the things that they have to have Lewy Bodies, and Lewy Bodies, from what I understand, have only been discovered in the past 20 years. It’s been named and figured out what in the world it is. I think a lot more research needs to go in… if they could have more research on that REM deficiency, they may be able to link it better, going forward. (CG12, wife) |
Whether more people have the same issue I have with the sleep. I don’t know if that’s been addressed because they seem to—the only drug they seem to be able to give you are anti-psychotic or something of that nature. And that’s the ones that zombie me out. (P8) | |
Parkinsonism | I know one of the things that occurs with me is the shaking—the tremors. That area that, research, I think I would encourage. (P3) |
And sometimes my wife says, she said this morning, “You’re shuffling around.” And I said, “No I’m not.” But I obviously was. And I don’t know if they can—I don’t know how many studies they’ve done on that. So I can’t really say, but—it seems an issue. (P8) | |
The moment that you show—the physical alteration show up, there is a really big part of the disease that you have missed studying. (CG18, wife) | |
He’s in this slow-mo… You know, everything’s a little slower. You know, tha movement issue, I guess—that comes with this also, that slows down your ability to just balance, and walk. (CG24, wife) | |
Postural instability, repeated falls | One of the biggest challenges I have we’ve kind of moved beyond falls a little bit. Now, we’re just more into mobility when another person becomes responsible for helping you be mobile. So, I’m not sure if that comes under a research category, but it would definitely be something that would be helpful to know more about. (CG13, wife) |
Orthostatic hypotension | Blood pressure is low. Blood pressure… Of course, I’m starting to feel a little bit dizzy from time to time. I have to really think about getting up slower, and I don’t walk down the road anymore, they was worried about me walking down the road. (P25) |
Well, I guess we could use the autonomic nervous effects there, I guess. Well, it’s like, the blood pressure dropping. You know, which can cause falls which are the worst. (CG9) | |
Urinary incontinence | Well, of course, the incontinence. You know? And that’s not something that he feels good about. He understands what’s going on with that and he doesn’t like it, but he doesn’t have a choice, you know, but to let me help him. But I have to fight for him to let me help him for a good while, you know? (CG3, wife) |
Constipation | She does have issues with constipation, an’ you know, most o’ the drugs and things we give her do help with that, but again, it’s another drug that has side effects… (CG2) |
Daytime sleepiness and fatigue | Daytime sleeping or need to nap. Well, when you don’t sleep more than four or five hours a night, you get sleepy in the daytime. (P25) |
I think for him, the worst thing is that he’s always tired. If you asked him what’s the worst thing, he would say, “I’m always tired.” (P19, wife) | |
Psychiatric symptoms (depression, anxiety, behavior changes) | It would be nice to have a magic pill that makes me- my very bad moods go away. (P28) |
He suffers a lot from depression and anxiety also… If they could address the depression and the anxiety, some of the other symptoms might not be as severe. (CG23, wife) | |
I think the one that affects him the most is the outbursts of anger. Like, he can just be fine, and then he’ll just set off into this rage. And he’ll eventually get over it, but sometimes it’s hours before he gets over it…. Well, that part of it would be the most important to me, too, because he’s not that kind of a person. If they could just somehow get control over that. But again, I—you know, I don’t even know what kind of research could do that. (CG4, wife) |
Many discussed that research should investigate the symptoms and also medications to help:
(P7)
(CG19, wife)
Participants also desired research on non-pharmacologic strategies to address DLB symptoms, including therapy, exercise, meaningful activities, “natural” therapies, changes in diet and nutrition, and unconventional approaches such as hyperbaric chambers.
(CG17, wife)
(CG6, wife)
Caregivers often wanted research on how to practically handle DLB symptoms in day-to-day life:
(CG17, wife)
(CG22, husband)
(CG5, husband)
(CG8, wife)
Multiple individuals with DLB and caregivers discussed the need for pharmacologic or non-pharmacologic disease-modifying therapies that will prevent, cure, or slow DLB:
(P4)
(CG2, daughter)
(CG5, husband)
(CG7, wife)
Multiple participants emphasized that research needs to focus on daily function:
(CG13, wife)
(CG16, wife)
Individuals with DLB and caregivers offered many topics pertaining to daily life that they felt were deserving of more research, including how to maintain socialization, maintain the ability to drive, identify emergencies, keep individuals with DLB safe, communicate well between couples (patient-caregiver), find support (e.g. good healthcare providers, external programs), handle non-DLB healthcare issues, make medical decisions, and strategize long-term planning. Research aiming to improve quality of life was another common theme, particularly from caregivers:
(CG7, wife)
(CG25, wife)
Several individuals with DLB and most caregivers identified the need for additional research addressing different realms of caregiving, including caregiver burden and support, depression and how to handle impatience and frustration, balance external work and caregiving, identify alternative care options and ways to keep the individual with DLB at home, and identify resources to pay for caregiving needs.
(CG14, wife)
(CG10, wife)
Almost all caregivers and half of participants with DLB described a need for improved education surrounding DLB and how research could improve educational efforts. While these opinions were provided in response to questions about research, it was sometimes unclear whether participants were expressing a need for more education clinically or a specific desire for research on this topic. Participants described a need for education in general and also specifically for physicians, medical trainees, therapists, patients, and caregivers/families. The most commonly described needs were education for non-specialist healthcare professionals and for caregivers.
(P8)
(CG19, wife)
(P25)
(CG16, wife)
Most of the research topics queried in the interviews or mentioned by interviewees were identified by at least some participants as their top priorities for DLB research (
(CG3, wife).
Top Research Priorities | Exemplar Quotes |
---|---|
Focusing on awareness | Maybe putting some money into getting people more aware of it. (CG14, wife) |
Determining the cause | Figure out what is goin’ on… and what Lewy body is, and I’m just not sure about what is goin’ on…and why it’s causing so many changes. (P24) |
I would give the whole thousand dollars right into the protein. Because I think everything else that we talked about can be dealt with… if it’s the protein in the brain that is making lack of or too much, that is making these poor people get this disease, that’s what should be addressed. Because everything else would be taken care of. (CG4, wife) | |
Improving diagnosis | I don’t think $1,000.00 would cover any of it. Oh, God, I don’t know. I would say early—finding the symptoms earlier and hopefully they could see what leads up to it. Yeah, and this way here they could find out, you know, what is the symptom on? Is your-like, is your hand shakin’? Has your eyes changed? Has your skin tone changed?…. You know, there could be some kind of a telltale sign. (P4) |
I think I’d spend 50 percent of it on the diagnosis and understanding her conditions, which are done by testing, and your laboratories… (CG1, husband) | |
The imaging research I would say is very, very important. I would like to see that progress… (P28) | |
Investigating what to expect and disease stages | What is expected with each passing stage, as it appears? (CG12, wife) |
DLB symptoms needing additional research | To me the most important is his cognition. (CG23, wife) |
On movement and—no, I think if you spread [the research money] too thin, that’s not good, so…I mean, really. (P22) | |
They need to do research on the physical. (CG19, wife) | |
And the rest [of the research money] on coping strategies and how to lessen the symptoms as much as possible and increase the quality of life. (CG22, husband) | |
Need for therapies to prevent, cure, or slow DLB | The most important thing would be tryin’ to make sure there is a cure for this horrible disease for anyone it affects, not just my loved one, but anybody that is affected by it. (CG7) |
Research on daily function, daily life, and quality of life | I would divide it number one on quality of life and specifically into the hallucinations and the sleeping. (P8) |
I would spend 25% on supportive improvement of lifestyle. (P18) | |
Quality of life. A hundred percent… Having an overarching focus on quality of life, your symptoms answer themselves. For us, it’s all quality of life. (CG5, husband) | |
50 percent towards quality of life…I think it all really boils down to the daily ins and outs. (CG12, wife) | |
Research on caregiving | I guess probably, how, how we can help the caregivers be more successful, or have better lives—as opposed to brain changes. (P20) |
Caregiver respite—all of it [the research money]…. If the caregiver’s not well, nobody’s well… Ways to incorporate respite for the caregiver or the patient… I think caregiver patient respite I would spend the whole $1,000 on that… (CG8, wife) | |
Research on improving education | If you can’t—you ain’t got no knowledge or nothin', none of the rest of it would matter to you anyway. (P17) |
Education for patients and for the doctors. Nurses, psychologists, all those people. Well, I mean if I just had $1,000.00 that would be the most important thing to me. (P25) | |
I would say from my point of view, I would say that we really need more education for other—for the people around [patient] (CG1, husband). | |
I would do at least a quarter of it in information to the patient and the caregiver—just ‘cause I think it’s so important. (CG20, wife) |
The study guide queried a variety of research categories and individuals with DLB and caregivers identified topics important for research in all of them—focusing on awareness, determining the cause of DLB, improving diagnosis, investigating what to expect and disease stages, DLB symptoms needing additional research, therapies to prevent, cure, or slow the progression of DLB, targeting daily function and quality of life, caregiving, and improving education. Furthermore, when participants were prompted to assign virtual money to research topics and identify their highest research priorities, at least one participant endorsed each of these areas. This highlights that research is needed across the DLB spectrum—basic science, translational, biomarker, natural history, drug development/therapeutic, quality improvement, and outcomes.
Published Lewy body dementia research priorities were developed primarily by experts and focus on disease mechanisms and processes (including animal model development), diagnostic criteria, terminology, risk factors/prodromal stages, longitudinal cohorts, pathological staging, imaging, biomarkers, genetics, new treatment targets, and preventative/disease-modifying and symptomatic treatments [
Recommendations form the 2017 National Research Summit on Care, Services, and Supports for Persons with Dementia and Their Caregivers address some of the themes from current study participants—the need for research to understand different dementia trajectories, determinants of behavioral and psychological symptoms, caregiving, decision-making, and support and financial considerations, as well as research investigating pharmacologic and non-pharmacologic treatment strategies and studying complex, multicomponent programs accommodating care needs [
In this study, individuals with DLB and caregivers described several topics as needing research which professionals might put in the category of clinical care. For example, the need for more education across populations was a common theme. Many participants mentioned needs relating to daily life (decision making, independence including driving, socialization), practical caregiving considerations, when and how to obtain and use extra support, and finances. These practical research priorities are consistent with previously published research priorities of individuals with dementia and their caregivers. The top six overall research priorities identified through modified Delphi consensus involving participants from dementia advocacy organizations were (1) cure and treatment, (2) caregiving, (3) education and training, (4) quality of life, (5) complementary therapies, and (6) care settings [
Differences in research priority-setting studies likely reflect the populations participating (e.g. country of origin; combination of patients, caregivers, advocates, healthcare professionals), the types of dementia represented, and the focus of the organizers or project leadership. The current study is also distinct from prior formal priority-setting work, as the goal of the current project was to investigate the views of individuals with DLB and caregivers at a single center, and not to use survey or formal consensus-building processes to build a top-ten list. The current results could serve as background for such a project specific to DLB. Regardless of methodology, it is clear from the current study and prior work that individuals with dementia and caregivers of individuals with dementia, including DLB, prioritize research targeting issues relating to living with disease alongside efforts to better understand the cause of DLB and identify a cure.
Indeed, research into the topics discussed by participants is sorely needed. It is estimated that that 1 in 3 cases of DLB may be missed [
This study is the first to evaluate the research priorities of individuals living with DLB and caregivers of individuals with DLB. This study can inform survey development to identify research priorities of a larger group of individuals living with DLB, serve as the background for formal research priority-setting in DLB, and help guide research planning. The study recruited individuals with DLB and caregivers from a single United States-based center of excellence, affects generalizability, though the identified topics were consistent with publications enrolling stakeholders with other dementias and PD. It is plausible that a different cohort could have identified different or additional themes. For example, because enrolled individuals with DLB had to have mild-moderate dementia (such that they could participate), they and the caregivers who enrolled with them as part of dyads may not have considered end of life research questions, which could potentially be a priority for families dealing with advanced DLB. Furthermore, interview questions were open-ended within categories and additional prompting regarding research topics could have resulted in different responses. The study specifically sought the opinions of individuals with DLB to give them an active voice and role, but several of the participants struggled to understand and answer the questions or perseverated on certain answers, limiting the information that could be gained from those interviews. Most participants were of white non-Hispanic backgrounds and had high educational attainment, potentially affecting generalizability. Similarly, most participating caregivers were wives and it is plausible that other caregiving roles (e.g. husbands, children caring for parents) would have different priorities.
Individuals with DLB and caregivers of individuals with DLB identified areas needing more research related to DLB awareness, causation, diagnosis, prognosis and DLB stages, core and supportive symptoms, disease-modifying and symptomatic treatments, issues relating to daily function and quality of life, caregiving, and education across populations. These findings support the research priorities defined in the NIH care summits in addition to the NIH ADRD summits. Further research is needed across all domains of DLB. Research funding should be informed by the priorities of all relevant stakeholders and support research investigating causes, natural history, biomarkers, and treatment in addition to research targeting themes regarding living with this disease (e.g. independence, quality of life, caregiving, and education).
COREQ 32-item checklist outlining the page where each element of qualitative research is reported.
(DOCX)
(DOCX)
Codebook with themes, subthemes, and supporting quotes (with respondent identifiers removed to preserve participant confidentiality).
(XLSX)
PONE-D-20-18287
Research Priorities of Caregivers and Individuals with Dementia with Lewy Bodies: An Interview Study
PLOS ONE
Dear Dr. Armstrong,
Thank you for submitting your manuscript to PLOS ONE. After careful consideration by 2 Reviewers and an Academic Editor, there is a somewhat discrepant view of the submission. Accordingly, all of the critiques of Reviewer #2 must be addressed in detail in a revision to determine publication status. If you are prepared to undertake the work required, I would be pleased to reconsider my decision, but revision of the original submission without directly addressing the critiques of Reviewer #2 does not guarantee acceptance for publication in PLOS ONE. A revised submission will be sent out for re-review. The authors are urged to have the manuscript given a hard copyedit for syntax and grammar.
==============================
1. Is the manuscript technically sound, and do the data support the conclusions?
The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.
Reviewer #1: Yes
Reviewer #2: Partly
**********
2. Has the statistical analysis been performed appropriately and rigorously?
Reviewer #1: Yes
Reviewer #2: N/A
**********
3. Have the authors made all data underlying the findings in their manuscript fully available?
The
Reviewer #1: Yes
Reviewer #2: No
**********
4. Is the manuscript presented in an intelligible fashion and written in standard English?
PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.
Reviewer #1: Yes
Reviewer #2: Yes
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5. Review Comments to the Author
Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)
Reviewer #1: This is an important and well written study, and gives new perspectives about carer and persons with DLB. Hopefully there will be follow up studies, that also can look into if there are any differences as the DLB progress.
Reviewer #2: The study evaluates the research priorities of DLB patients and their caregivers.
It is an original topic in line with the important topic of consumers’ empowerment which should include decisions in research planning, as well as care.
As far as the “Review Questions” are concerned:
1.One of the aim of the researchers was to address possible significant differences between DLB and other dementias or parkinsonisms, since prior publications reporting on research priorities in PD or “dementia” could not have captured the priorities specific for DLB. However,I was not able to understand what specific issues, different form dementia/parkinsonism in general, emerged in this small cohort.I suggest to discuss in depth whether you found differences in research priorities/claims which are specific to DLB.
A great limit of the study is that it is a single-center based interview study; this fact deeply affects generalizability.It should be stressed that the study has the characteristics of a pilot/feasibility study to assess methodology and important parameters and issues that are needed to design a study with a larger sample population with more possibilities to generalize the results, in particular the saturation of all themes of interests.
As a clinician, I have some difficulties in judging the technical correctness of the qualitative descriptive approach used. I suggest to describe more in depth the methodology quoting original references and not referring to similar studies (ref. 16 and 17). Describing that Microsoft Word® and Excel 2016® were used to organize data and themes is pleonastic.
The following statements seem to be contradictory: if “this study is the first to evaluate the research priorities of individuals living with DLB” (I can’t confirm this...I did not review literature systematically) you cannot write that “the identified topics were consistent with other Publications”.
2.Since a qualitative descriptive approach was used, quantitative statistical analysis was not carried out. See point 1 for the need of more details on qualitative approach and data analysis.
3.Since the qualitative nature of the study, it is important to have some examples from the interviews but not all data underlying the findings described.
Other comments:
Row 79: I suggest “may” fail ...
Row 88: I suggest to use the term Lewy Body Disease (LBD according to professor Kosaka)
Row 92 I suggest to use the term “dream enactment behavior”
Rows 437-8 “Caregiver burden in DLB is high [17-19] and quality of life is worse in DLB compared to AD dementia [33, 34].”I suggest to move this phrase with adequate correction in Introduction where this concept has been already given.
You wrote that individuals with DLB and their caregivers offered many topics pertaining to make medical decisions and strategize long-term planning. In your interview came out the need of tools to enhance Advance Care Planning (ACP)? Did the topic of managing end-of-life issues emerge?
I would like to know whether the topics of ACP and Palliative Care (PC) emerged in the interviews, and how these topics were classified: as “quality of life” or “what to expect and disease stages”, “decision making”, “support to caregivers” or “Long term plans” (fig 1). Why not under a specific topic “ACP”? Please, discuss about it. If these topics did not emerge, discuss why. I think it will be of interest to know if there are some cultural issues to deal with ACP and PC in disease like DLB in your geographical/social context. I was impressed by the fact that two caregivers “didn’t see value in earlier diagnosis without disease-modifying treatments”. This fact seems to open the question that early diagnosis may not be considered important for defining ACP and, more in general,advance provisions for life (and death) preferences before the patient progressed to a dementia level which is not compatible with a decision/preference making.
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"I have read the journal's policy and the authors of this manuscript have the following competing interests: MJA receives research support from ARHQ (K08HS24159), a 1Florida ADRC pilot grant (AG047266), the Florida Department of Health Ed & Ethel Moore research program, and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. AT is employed by the Lewy Body Dementia Association. BP receives research support from an American Academy of Neurology Clinical Research Training Scholarship in Lewy Body Dementia. GS receives research support from the 1Florida ADRC (AG047266) and the Florida Department of Health Ed & Ethel Moore research program."
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[This was uploaded as a separate file with formatting but we are also cutting and pasting the response below.]
Reviewer #1:
Reviewer: This is an important and well written study, and gives new perspectives about carer and persons with DLB. Hopefully there will be follow up studies, that also can look into if there are any differences as the DLB progress.
Response: Thank you. (Nothing to do.)
Reviewer #2:
Reviewer: The study evaluates the research priorities of DLB patients and their caregivers.
It is an original topic in line with the important topic of consumers’ empowerment which should include decisions in research planning, as well as care.
Response: N/A
Reviewer: As far as the “Review Questions” are concerned:
1.One of the aim of the researchers was to address possible significant differences between DLB and other dementias or parkinsonisms, since prior publications reporting on research priorities in PD or “dementia” could not have captured the priorities specific for DLB. However,I was not able to understand what specific issues, different form dementia/parkinsonism in general, emerged in this small cohort.I suggest to discuss in depth whether you found differences in research priorities/claims which are specific to DLB.
Response: To clarify, the aim of the project was “to identify the research priorities of individuals with DLB and caregivers…” (pages 4-5). It was not an aim to address possible significant differences between DLB and other dementias or parkinsonisms (this would need a separate design, such as a study enrolling all 3 populations). The reference to the other diseases in the introduction is because the authors felt that the priorities in DLB could be different from other dementias and Parkinson disease because of meaningful differences in disease experiences and trajectories, and this provided the rationale for the current project. While addressing differences between diseases was not an aim, we agree that this is important for the discussion. Some of this information was already present, but we have edited the paragraph to reflect both of the referenced PD publications and not just the dementia publications: “These practical research priorities are consistent with previously published research priorities of individuals with dementia and their caregivers. The top six overall research priorities identified through modified Delphi consensus involving participants from dementia advocacy organizations were (1) cure and treatment, (2) caregiving, (3) education and training, (4) quality of life, (5) complementary therapies, and (6) care settings [23]. Similarly, dementia priority setting through the James Lind Alliance identified 10 research priorities, including maintaining independence, optimal care, pharmacologic and non-pharmacologic care, and caregiver support [22]. A more recent dementia priority setting process in Canada identified 10 research priorities including investigating stigma, supporting emotional well-being, early treatment, health system changes, caregiver support, connection to education and support, necessary dementia-related skills and knowledge for healthcare professionals, dementia-friendly communities, best dementia practices, and non-pharmacologic treatments [25]. Research priority setting for people with PD dementia identified needed research on physical functioning, symptoms, coping, stress, socialization, relationships, support, autonomy, and good care and communication alongside prioritizing research addressing PD causes, diagnosis, subtypes and medication for both motor and non-motor symptoms [22, 23].” (page 22, lines 418-419, tracked changes version)
Reviewer: A great limit of the study is that it is a single-center based interview study; this fact deeply affects generalizability.It should be stressed that the study has the characteristics of a pilot/feasibility study to assess methodology and important parameters and issues that are needed to design a study with a larger sample population with more possibilities to generalize the results, in particular the saturation of all themes of interests.
Response: We have edited the sentence in limitations to be clear that the subject group affects generalizability: “The study recruited individuals with DLB and caregivers from a single United States-based center of excellence, which affects generalizability, though the identified topics were consistent with publications enrolling stakeholders with other dementias and PD. It is plausible that a different cohort could have identified additional themes.” (Page 23, lines 450-451, tracked changes version). We agree that one hope of these results is to inform planning of a larger study: “This study can inform survey development to identify research priorities of a larger group of individuals living with DLB, serve as the background for formal research priority-setting in DLB, and help guide research planning.” (Page 23, lines 445-447, tracked changes version). This study was not designed to assess methodology, however; it used an established qualitative methodology technique (now better reflected in the correct references, see below).
Reviewer: As a clinician, I have some difficulties in judging the technical correctness of the qualitative descriptive approach used. I suggest to describe more in depth the methodology quoting original references and not referring to similar studies (ref. 16 and 17). Describing that Microsoft Word® and Excel 2016® were used to organize data and themes is pleonastic.
Response: We apologize; there was an error in our references and this was indeed very confusing. The references 16 and 17 in the submitted manuscript were incorrect; it appears that they were converted to plain text too early so that the original references were lost. We have added the appropriate references: Colorafi 2016 describes qualitative descriptive approaches and Tong 2007 is the reference for reporting qualitative studies. We have maintained the reference to the use of Microsoft Word and Excel because item #27 of the COREQ checklist for qualitative research reporting (S1 checklist) is the software used (i.e., reporting the software use is parting of the reporting checklist for qualitative studies). While the use of Word and Excel is somewhat mundane, we are required to clarify that we did not use some of the purchasable qualitative research software available such as NVIVO. (Methods section, “Study design,” page 5, tracked changes version.) We select qualitative software by project and this one was served well by Word and Excel and did not require advanced qualitative software packages.
Reviewer: The following statements seem to be contradictory: if “this study is the first to evaluate the research priorities of individuals living with DLB” (I can’t confirm this...I did not review literature systematically) you cannot write that “the identified topics were consistent with other Publications”.
Response: We have clarified the sentence to read “…, though the identified topics were consistent with publications enrolling stakeholders with other dementias and PD” (page 23, line 450, tracked changes version).
Reviewer: 2.Since a qualitative descriptive approach was used, quantitative statistical analysis was not carried out. See point 1 for the need of more details on qualitative approach and data analysis.
Response: We have now added the correct reference for the qualitative descriptive response (“study design,” first paragraph of methods, page 5 of tracked changes version). The correct reference was also added to the “data collection and analysis” section (line 151, tracked changes version). Details of how the qualitative analysis was performed is also captured in this section (page 7, lines 150-160, tracked changes version): “Investigators used tables in Microsoft Word® and Excel 2016® to organize data and a qualitative descriptive approach to identify and organize themes [26]. Broad topics/categories were defined by interview questions, but themes were identified from interview transcripts. The PI and two research assistants independently analyzed interview transcripts to create a codebook and then reached consensus regarding emerging themes (open coding). The research assistants analyzed remaining transcripts using a constant comparative technique, revising themes and subthemes with the PI if needed (axial coding) (S3 File). Coders assessed saturation during analysis. Co-investigators gave feedback after the initial coding. Participants were numbered in the analysis such that participants who enrolled in the study as a dyad shared participant numbers (with “P” indicating patient participants and “CG” indicating caregiver participants).”
Reviewer: 3.Since the qualitative nature of the study, it is important to have some examples from the interviews but not all data underlying the findings described.
Response: There are different approaches to qualitative analyses. Some qualitative analyses simply state the synthesized ideas without many quotes. A qualitative descriptive approach, however, presents quotes that provide examples for the identified themes/subthemes. The examples included do not reflect all the underlying data, but serve as illustrative quotes. We tried to include, where possible, one quote from a patient and one quote from a caregiver to demonstrate these themes across populations (where appropriate). In response to this comment and the editor’s comment, we have now included a de-identified supplemental Excel file (S3 File) showing the underlying data.
Reviewer: Other comments: Row 79: I suggest “may” fail ...
Response: We have not made this change because by definition, consultation strategies do not give patient representatives an active voice in the process. Consultation strategies ask for opinions but do not actively include a representative as a co-participant. If a person has an active voice in the process, that is by definition a “participation” strategy.
Reviewer: Row 88: I suggest to use the term Lewy Body Disease (LBD according to professor Kosaka)
Response: We have revised the sentences to read, “DLB is a subset of Lewy body dementia, the 2nd most common neurodegenerative dementia in the United States [8]. DLB is a dementia with clinical and pathological overlap with Parkinson disease (PD) and both fall in the pathological category of Lewy body diseases.” (Page 4, lines 88-90, tracked changes version)
Reviewer: Row 92 I suggest to use the term “dream enactment behavior”
Response: Changed to “dream enactment behavior” as suggested (page 4, line 93, tracked changes version)
Reviewer: Rows 437-8 “Caregiver burden in DLB is high [17-19] and quality of life is worse in DLB compared to AD dementia [33, 34].”I suggest to move this phrase with adequate correction in Introduction where this concept has been already given.
Response: We have added the sentence “Quality of life is also worse in DLB compared to AD dementia [20, 21]” to the introduction on page 4 as suggested (line 97, tracked changes version). We have no fully removed these concepts from the discussion, because this paragraph is providing context for why research into the topics discussed by participants is needed. We have reworded the paragraph (page 23, lines 433-442, tracked changes version) to read: “Indeed, research into the topics discussed by participants is sorely needed. It is estimated that that 1 in 3 cases of DLB may be missed [32] and initial misdiagnosis is common [32, 33]. It takes over a year for half of individuals with DLB to receive a diagnosis [33]. Family members of individuals who died with DLB described both lack of knowledge of what to expect and negative experiences relating to lacking healthcare professional education and knowledge [12, 34, 35]. While α-synuclein deposition has been the presumed pathogenic cause of DLB for years, recent re-analysis questions this assumption [36]. There are no biomarkers for DLB and no treatments for DLB approved by the U.S. Food and Drug Administration. Caregiver burden in DLB is high [17-19] and quality of life is negatively affected by DLB [20, 21].”
Reviewer: You wrote that individuals with DLB and their caregivers offered many topics pertaining to make medical decisions and strategize long-term planning. In your interview came out the need of tools to enhance Advance Care Planning (ACP)? Did the topic of managing end-of-life issues emerge?
Response: Advance care planning came up in the portion of the interviews about clinical care (the first half of the interviews), but not in the portion of the interviews about research priorities, which is the topic of the current analysis and manuscript. Sadly to us, since several of the researchers on this paper research the end of life in dementia with Lewy bodies, this was not a major theme in the voiced research priorities.
Reviewer: I would like to know whether the topics of ACP and Palliative Care (PC) emerged in the interviews, and how these topics were classified: as “quality of life” or “what to expect and disease stages”, “decision making”, “support to caregivers” or “Long term plans” (fig 1). Why not under a specific topic “ACP”? Please, discuss about it. If these topics did not emerge, discuss why. I think it will be of interest to know if there are some cultural issues to deal with ACP and PC in disease like DLB in your geographical/social context. I was impressed by the fact that two caregivers “didn’t see value in earlier diagnosis without disease-modifying treatments”. This fact seems to open the question that early diagnosis may not be considered important for defining ACP and, more in general,advance provisions for life (and death) preferences before the patient progressed to a dementia level which is not compatible with a decision/preference making.
Response: As noted above, ACP and palliative care were not mentioned during the research portions of the interviews. While we agree that these topics overlap with some of the other themes mentioned, ACP and palliative care as specific research topics were not identified themes. We have added a discussion of this to the limitations section (pages 23-24, tracked changes version): “It is plausible that a different cohort could have identified different or additional themes. For example, because enrolled individuals with DLB had to have mild-moderate dementia (such that they could participate), they and the caregivers who enrolled with them as part of dyads may not have considered end of life research questions, which could potentially be a priority for families dealing with advanced DLB. Furthermore, interview questions were open-ended within categories and additional prompting regarding research topics could have resulted in different responses.”
Journal Requirements/Other Comments:
While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,
Response: We used PACE and have revised our image accordingly.
1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at
Response: We re-reviewed the style requirements and made a couple small adjustments.
2. Thank you for stating the following in the Competing Interests section:
"I have read the journal's policy and the authors of this manuscript have the following competing interests: MJA receives research support from ARHQ (K08HS24159), a 1Florida ADRC pilot grant (AG047266), the Florida Department of Health Ed & Ethel Moore research program, and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. AT is employed by the Lewy Body Dementia Association. BP receives research support from an American Academy of Neurology Clinical Research Training Scholarship in Lewy Body Dementia. GS receives research support from the 1Florida ADRC (AG047266) and the Florida Department of Health Ed & Ethel Moore research program."
Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors
Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.
Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests:
Response: We re-reviewed all the authors’ disclosures (one small adjustment not relevant to the paper) and added the requested statement. This is all in the cover letter.
3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see
Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see
Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data:
We will update your Data Availability statement to reflect the information you provide in your cover letter.
Response: We did not originally upload the full analysis because of concerns that the participants could be identifiable. To meet this requirement, we have removed the participant attribution from each quote in the coding. We have now added the S3 file with the codebook and the underlying quotes (but without the attribution for each quote, which we maintain).
Submitted filename:
Research Priorities of Caregivers and Individuals with Dementia with Lewy Bodies: An Interview Study
PONE-D-20-18287R1
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Reviewer #1: Looking forward to read more about this topic and hoping the authors have further plans for following up studies!
Reviewer #2: I'm grateful to the Authors for addressing the topics of ACP and PC. The fact that ACP and PC were not mentioned during the interviews as specific research topics deserves further attention and discussion beyond this paper's aims. I will be glad to further discuss and disseminate this result, even in a further publication aimed at trying to gain an in-depth understanding of why ACP and PC did not emerge as specific topics.
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PONE-D-20-18287R1
Research Priorities of Caregivers and Individuals with Dementia with Lewy Bodies: An Interview Study
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