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Research priorities of caregivers and individuals with dementia with Lewy bodies: An interview study

Background 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. Method 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. Results 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. Conclusions 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).


Introduction
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 [1,2]. Before studies are even initiated, patients, caregivers, and the public have a role in identifying research priorities [2]. This is critical given a mismatch between the research priorities of patients, caregivers, clinicians, and researchers [3].
The Advisory Council on Alzheimer's Research, Care and Services recommends that all funders "should establish the engagement of the AD/ADRD [Alzheimer disease/ Alzheimerdisease related dementia] community as a standard practice in. . . participating in setting national research priorities for AD/ADRD. . ." [4]. The NIH has adopted multiple strategies to increase the role of patient and public involvement in dementia priority setting. ADRD national research priority summits include sessions led by nongovernmental organizations to increase non-expert stakeholder input and public-private partnerships [5]. The 2017 National Research Summit on Care, Services, and Supports for Persons with Dementia and Their Caregivers included "persons living with dementia" and family caregiver stakeholder groups as two of the six stakeholder groups informing summit planning and recommendations [6]. One aim of the planned 2020 National Research Summit on Care, Services, and Supports for Persons with Dementia and their Caregivers was to develop recommendations for research priorities to inform federal agencies and other research funders, but the in-person meeting was cancelled due to the global COVID-19 pandemic. The summit will now occur via a series of virtual meetings in summer 2020.
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 [7].
Stakeholders representing individuals with Lewy body dementia participated in NIH AD/ ADRD priority setting [5] and the 2017 care summit [6]. However, no prior research investigates the research priorities of individuals and caregivers living with dementia with Lewy bodies (DLB). DLB is a subset of Lewy body dementia, the 2 nd 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. However, DLB has important differences from both PD and AD/other dementias which could meaningfully impact research priorities. For example, symptoms such as cognitive fluctuations, hallucinations, and dream enactment behavior distinguish individuals with DLB from AD [9]. Individuals with clinically-diagnosed DLB survive a median of 3-4 years after presentation [10][11][12], shorter than individuals with PD [13,14] or AD dementia [11,15]. Caregiver burden in DLB may be similar to PD dementia [16], but it is higher in DLB compared to AD dementia [17][18][19]. Quality of life is also worse in DLB compared to AD dementia [20,21]. Given these and other important differences between DLB and other dementias and parkinsonisms, prior publications reporting on research priorities in PD [22,23] and dementia in general [24][25][26][27] may not capture the priorities of individuals with DLB. We thus aimed to identify the research priorities of individuals with DLB and caregivers, particularly to guide research at our center.

Study design
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 [28] to analyze interview transcripts. A qualitative descriptive approach involves reporting and summarizing straightforward accounts of participants' views without an intent to generate or test theory. A qualitative descriptive approach was employed given the aim of identifying research priorities, rather than investigating theories underpinning those priorities. Consolidated criteria for reporting qualitative research guided study reporting (S1 Checklist) [29].

Population and recruitment
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 [9] or caregiver for an individual diagnosed with DLB, (3) if a person with DLB, clinician-judged mild-moderate severity such that the individual could understand the study and provide personal opinions, and (4) willingness to participate in a telephone interview. Individuals and caregivers were not required to participate as a dyad. Participants were recruited when presenting for routine clinical visits or through a consent-to-contact research database at the institute. The University of Florida institutional review board provided approval (IRB201500996). The study used a waiver of documentation of informed consent.

Data collection and analysis
The PI (MJA), a DLB specialist, drafted the semi-structured interview guide (S1 File) and revised it based on suggestions from a neuropsychologist (GS), a dementia specialist (not further involved in the project), PhD specializing in qualitative research (TM), and former caregiver of an individual with DLB (AT). The interview included questions regarding clinical care priorities, which will be analyzed separately. Research questions asked about participant priorities for DLB research in general and then specifically queried participant priorities regarding research on DLB symptoms, daily challenges, caregiving/family life, and diagnosis. Finally, the interview guide asked the participant to identify how they would divide $1000 to spend on DLB research and to prioritize what research was most important to them.
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 1 and Excel 2016 1 to organize data and a qualitative descriptive approach to identify and organize themes [28]. 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) (S2 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).

Demographic and interview characteristics
Interviews occurred between 1/22/2018 and 5/6/2019. Twenty individuals with DLB and 25 caregivers participated (Table 1). Seventeen from each group participated as part of a patient-  Well, maybe the breaker tripped. Maybe the bulb burned out. Maybe the wire broke." You know, there's a lotta maybes.

(P4)
Well, you've got to find the root cause. . . You know, you find the cause or the problems, and you can treat it or correct it.
(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.

Improving diagnosis
Multiple individuals with DLB and almost half of caregivers discussed the importance of research to improve early diagnosis ( Table 2). While these respondents discussed the need for earlier diagnosis, particularly in circumstances where a diagnosis was delayed, one individual (CG22, husband) Multiple individuals with DLB and caregivers described needing more research to help individuals with DLB, caregivers, and healthcare professionals recognize the signs of DLB (Table 2). Caregivers wanted research to focus on improving the accuracy of diagnosis, including distinguishing DLB from PD and dementia generally, particularly given widespread confusion regarding Lewy body terminology. Several individuals with DLB and caregivers desired more research into tests and biomarkers to assist with DLB diagnosis (

DLB symptoms needing additional research
Participants highlighted the need for more research for many of the core and supportive features of DLB (Table 3) [9].
Many discussed that research should investigate the symptoms and also medications to help: Medicine-trying to find the right combination.

(P7)
Anything you can give him to tamp down his symptoms-anything you can give to make it so it's easier for him to exercise, it's easier for him to live his daily life, is very important.
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.

Need for therapies to prevent, cure, or slow DLB
Multiple individuals with DLB and caregivers discussed the need for pharmacologic or nonpharmacologic disease-modifying therapies that will prevent, cure, or slow DLB: How it could possibly be prevented or mitigated or slowed down in its decline.
(P4)  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 longterm planning. Research aiming to improve quality of life was another common theme, particularly from caregivers:

Research on caregiving
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.

Research on improving education
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.
I think there should be probably some more, uh, I guess they have to have yearly training or whatever, you know. I think that should be something that's sort of at the forefront, because so many doctors don't even know what you're talkin' about when you tell 'em your disease. And, you know, all of them, a lot of 'em.

(P8)
Education for regular doctors would be really good.
(CG19, wife) [It] would be helpful for everybody to have a caregiver course, to help take care of the person, but also to learn how to take care of themselves.

Ranking research priorities
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 (Table 4). Symptoms described as priorities for research included cognition, hallucinations, movement, mobility, sleep, and mood. A few participants mentioned that obtaining the patient and caregiver voices is the most important thing to them. (CG3, wife).

Discussion
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 [5,30]. The individuals with DLB and caregivers in this study supported and prioritized research on many of these topics. However, many topics proposed in this study were outside the national research priorities, possibly because the ADRD summit aimed to inform prevention and effective treatment of AD/ADRDs [5]. Individuals with DLB and caregivers described needing symptomatic treatments but also more research on topics pertaining to how families should handle DLB symptoms in daily life, improving daily life in general, targeting quality of life, caregiving research, understanding disease progression, and improving education regarding DLB across populations (public, patients, caregivers, healthcare professionals).
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 nonpharmacologic treatment strategies and studying complex, multicomponent programs accommodating care needs [31]. The care summit also identified the need to understand what outcomes are important to persons living with dementia and to engage persons living with dementia and caregivers as part of research teams [31]. Nearly half of the final research recommendations expressed ideas contributed by the persons living with dementia summit working group [6]. This emphasizes the need for funders (federal and otherwise) to consider research priorities from both dementia summits (ADRD and caring) when developing funding announcements and selecting projects to support.
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 [25]. 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 [24]. 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, dementiafriendly communities, best dementia practices, and non-pharmacologic treatments [27]. Research priority setting for people with PD 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].
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 [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][18][19] and quality of life is negatively affected by DLB [20,21].
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).