Medicines management issues in dementia and coping strategies used by people living with dementia and family carers: A systematic review

Objectives Medicines play a key role in the lives of people with dementia, primarily to manage symptoms. Managing medicines is complex for people with dementia and their family carers and can result in multiple problems leading to harm. We conducted a systematic review to identify and model medication issues experienced and coping strategies used by people with dementia and/or family carers. Methods Eleven general databases and four systematic review databases were searched. Studies were quality assessed using an established framework and thematically analysed. Results Twenty‐one articles were included in this study, and four domains affecting medication use were identified: cognitive, medication, social and cultural, and knowledge/educational and communication. People with dementia reported medication issues in all four domains, but few coping strategies were developed. Family carers reported issues and coping strategies related to the medication and knowledge/educational and communication domains. Common issues with regards to knowledge and communication about medicines remain unresolved. The “voices” of people with dementia appeared largely missing from the literature so were in‐depth understanding of how, whether, and in which circumstances coping strategies work in managing medicines. Conclusions Medicines management is a complex set of activities and although current coping strategies exists, these were primarily used by family carers or the person with dementia‐carer dyad. Health and social care practitioners and researchers should seek to understand in‐depth the “mechanisms of action” of existing coping strategies and actively involve people with dementia as co‐producers of knowledge to underpin any further work on medicines management.

with no cure presently available or on the immediate horizon, 4 this figure is projected to increase to two million by 2050. 5 The current cost of dementia in the UK is an estimated £26bn and projected to more than double to £55bn in 2040. 5 The real impact of dementia, however, extends beyond economics and includes the health, social, and emotional lives of individuals, their families, and wider society. [5][6][7][8][9] Although there is currently no cure for dementia, medicines play a key role in the lives of people with dementia, primarily to manage symptoms. 10 Some people with dementia may also be prescribed medication for comorbid health conditions such asType 2 Diabetes Mellitus or high blood pressure. 11 Unsurprisingly, given their cognitive problems, managing medication is complex for people with dementia which can result in "medication errors, medication related hospital admissions, and dependence on others to assist with medication management tasks". 12 Although non-adherence to medication is a widespread problem across conditions, ages, and other demographics, and can be intentional or unintentional, 13 cognitive impairment and dementia have been shown to specifically impact on medication adherence.
With more than two thirds of people with dementia living in the community in the UK, and supported in their daily living by around 670 000 family carers, 5 there is a need to understand how medicines are being managed or not, in this setting. Such knowledge is important so that health and social care practitioners, and researchers, can focus their work on supporting existing practices and/or designing interventions to enable safe medicines management.
The aim of this systematic review was to identify and model medication issues experienced and coping strategies used by people with dementia and/or family carers.

| METHODS
This systematic review is reported according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research: the ENTREQ Statement. 14

| Inclusion criteria
Articles were eligible if they (1) reviewed or were designed to investigate specific challenges or barriers to medication adherence among people with cognitive impairment or with dementia or Alzheimer's disease living in their own home; (2) reviewed the role of informal carers or family carers in medication management for people with dementia; and (3) reviewed or designed to explore people with dementia, carers, and/or health care provider's views/perspectives/experiences/relationships or feelings towards medication use, adherence and management, associated barriers and suggested solutions. There were no restrictions on the type of methodology (qualitative, quantitative, or mix of both) reported in the study. Only articles published in peerreviewed journals were included. Articles that included study participants under 65 years old were excluded from the review. Searches were limited to the English language.

| Screening of studies
Two independent researchers (T.S. and R.L.) screened studies for inclusion in the study applying a priori inclusion and exclusion criteria.
They screened titles of studies for relevance then abstracts of retained studies. Full texts of retained references were then obtained and screened for eligibility. Reference lists of included studies were searched manually for potentially relevant studies that met the inclusion criteria. Any disagreements were resolved by further discussions and then consensus.

| Quality assessment
All qualitative studies were quality assessed using an established appraisal framework 15 by T.S. R.L. independently quality assessed a proportion of these studies. Any disagreements were resolved by discussion and then consensus. Before conducting a quality assessment Key points 1. Our study identified and modelled four key domains that influence the use of medicines: cognitive, medication, social and cultural, and knowledge/ education and communication.
2. Current coping strategies exists to manage medication issues but mainly used by family carers or the person with dementia-family carer dyad. 3. The "voices" of people with dementia appeared to be largely missing from reviewed studies. 4. Health and social care practitioners and researchers should seek to understand in-depth, the "mechanisms of action" of coping strategies and actively involve people with dementia as co-producers of knowledge to underpin any further work on medicines management.
of the studies, two screening questions were asked which were directly related to the research aim: 1. Does the paper report on findings from study/studies on medicine adherence or medicine compliance and cognitive impairment (CI)/dementia/Alzheimer's disease (AD) AND/OR Patient/carers experience with medicine adherence or CI or AD or dementia? 2. Is the research relevant to the synthesis topic?
If the answer to either one of these questions was "no," the study was excluded. Any disagreements were resolved by discussion and then consensus. If both answers were "yes," the appraisal process then proceeded to the next stage. This next stage involved appraisal of each paper on the following categories: aim, methodology, theoretical perspective, sampling, data collection, data analysis, research partnership relations, justification of data interpretation, transferability, relevance and usefulness, and overall assessment of study. 15 The appraisal process involved answering yes/no and elaborations on the items contained in the categories assessed. See Table 1 for details of items assessed within each category. Any studies that did not meet key appraisal criteria were excluded from the study (see Table 2).

| Data extraction
T.S. independently extracted the following information from qualitative studies and systematic reviews: authors, year of publication,     √ denotes "yes" and x denotes "no" to the key items appraised (marked a in Table 1).
country where study was conducted, aim of study, study design and methodology, study setting, sample size and participant information/ details of studies included (where relevant), and key findings.
Abstracting key findings from qualitative studies has been reported to be problematic, 44 and an approach to resolve this problem is to include all text included under "results" or "findings," the approach taken in this study. The same approach was taken for systematic reviews. In addition, quotes and results cited in systematic reviews were checked for their source and matched to the list of included studies. Full text articles of references which were not in the list were then obtained, screened for eligibility, quality assessed, and relevant data extracted.

| Data synthesis
Due to the heterogeneity of study designs, it was not possible to use a meta-analysis approach to analyse quantitative findings. A thematic synthesis 44 with a framework approach 45-47 was used instead.
A framework approach, a form of thematic analysis, was appropriate because the research question was focused on a targeted area as opposed to very broad or abstract topics 47 -that of challenges to medication management for people living with dementia and their informal carers. It was also important to ensure the context of each individual study was not lost and a framework approach enables comparison across and within individual cases or studies within the analysis process. 45,47 In addition, the framework matrix that was formed as part of the analysis process provides a systematic model for mapping and analysing data which is important for the two researchers (R.L. and T.S.) undertaking the review, who are from two different disciplinary backgrounds. 45 The following steps were undertaken in the synthesis 45-47 : 1. Familiarisation: researchers read through extracted data from an initial sample of studies (approximately [3][4][5]. Key ideas were identified from each of these studies. During this process, recurrent themes were identified.
2. Develop a thematic framework: a framework was then constructed based on the research aims and the recurrent themes identified during the familiarisation process.
3. Indexing: the thematic framework was then applied consistently to all study data.
4. Charting: data from the original studies were then lifted and placed within the appropriate thematic categories within the thematic framework.

5.
Mapping: the final stage in the process is to interpret and map the range, polarities, and similarities within the data.
Using a framework approach, the focus was on understanding the breadth and depth of challenges reported in studies rather than the frequency of these problems. The approach to the synthesis did not emphasise weighing data for example through counting how many times a particular challenge was reported. Each reported challenge was considered to be unique and of equal significance. If the same challenge was reported multiple times in multiple papers including systematic reviews, it was still included once in the synthesis.
T.S. and R.L. conducted the analysis through extensive and iterative discussions. Any disagreements were resolved by further discussions and then consensus.

| Ethical considerations
Ethical approvals were not required as the study was a systematic review of peer-reviewed studies. Figure 1 shows the article selection process. Following quality assessment of studies (shown in Table 2), a total of 21 articles were included FIGURE 1 Article selection for inclusion in the study in this study: 12 empirical studies and nine reviews (see Table 3). Of the 12 empirical studies, eight used qualitative methods of enquiry, 18,22,25,27,32,34,36,43 two used mixed methods (a combination of qualitative and quantitative approaches), 19,20 and two followed cross-sectional study designs using quantitative methodology. 27,39 Six studies were carried out in North America (five in the United States and one in Canada), three in Australia, and five studies were conducted in UK. Six of the systematic reviews included both quantitative and qualitative studies, 23,31,33,35,38,40 two only selected quantitative studies for review, 12,26 and one was conducted only on qualitative studies. 30 The key characteristics and main findings from included studies are presented in Table 3. In eight of the 12 empirical studies, the study design included people with dementia and family carers as participants. 19,20,22,25,27,28,36,43 However, only four of these studies interviewed matching dyads (people with dementia with their family carers). 19,20,36,43 Seven studies included people with dementia. 20,22,25,27,36,39,43 The study design in these studies included semistructured interviews (n = range 4-11 participants), 25,27,36,43 selfreporting of beliefs and barriers to medication non-adherence (n = 96), 39 assessment of performance on medication management tasks (n = 27), 20 and focus group (n = 19). 22 One study 39 compared the frequencies of barriers to medication adherence between people with dementia and adults with no cognitive issues.  Table 4).

| Key domains affecting medication use
The cognitive domain includes factors such as the impairment of cognition, typically involving problems related to memory and at least one other cognitive domain (language, visuospatial, executive function) as reported by people with dementia and/or carers. 12,23,25,27,34 In the medication domain, factors relating to obtain and use of medicines, 27 People with dementia can be affected by the changes in any of these four domains due to the inter-relationships among the domains.
A decline in cognitive ability affects people with dementia's ability to plan, execute, manage, and organize medicine-related tasks. 23 3.3 | Issues related to medication use and coping strategies Table 4 provides a summary of specific issues to medication use as reported by people with dementia and family carers alongside any coping strategies reported to address them. Exemplars in the form of quotes from included studies are also included in Table 4

| DISCUSSION
To our knowledge, this is the first systematic review that identified and modelled a range of system factors influencing the overall management use of medicines and matching coping strategies within four inter-related system domains, as expressed by people with dementia and/or family carers. Although there are existing systematic reviews investigating medication issues, they have focused specifically on medication non-adherence, 26 the overall health care experiences of people with dementia and their caregivers (not specific to medication management), 30 and the relationship between medication non-adherence and cognitive domains (eg, memory and executive functioning). 12 This current study modelled medication management issues and challenges within the wider medication management system (not restricted to the person or dyad, including but not restricted to factors affecting/associated with medication non-adherence, health care system-level issues related to medicines management), and mapped the interconnectivity among/between other system domains. It is important to present medication issues from a systems view rather than  Semi-structured individual interviews using a grounded theory approach.
Grounded theory. PLWD are able to sustain self-management of their medicines using established routines and strategies. As cognitive changes affect short-term memory, external strategies and task allocation were taken on by family members to support continuing independence of PLWD. The family member assumed the carer role as their concern for medication safety increased, but this role created stress and was a burden that was unacknowledged by the health professional.   33 To provide a narrative review of contemporary literature on medicines management by people with dementia or cognitive impairment living in the community, methods for assessing their capacity to safely manage medicines, and strategies for supporting independent medicines management.
A total of 306 articles on medicines management on people with dementia were retrieved and examined for relevance.

Narrative review
As cognitive impairment progresses, the ability to plan, organise, and execute medicine management tasks is impaired, leading to increased risk of unintentional non-adherence, medication errors, preventable medication-related hospital admissions and dependence on family carers or community nursing services to assist with medicines management. Self-report and informant report on ability to safely managing medication may be helpful but can be unreliable or prone to bias. Measures of cognitive function are useful but may lack sensitivity and specificity. Direct observation, using a structured, standardised performance-based tool, may help to determine whether a person is able to manage their medicines and identify barriers to adherence such as inability to open medicine packaging.
Gillespie et al.
(2014) 31 To explore published literature that describes what is known about the role of informal caregivers as they manage medications for older adults and/or people living with dementia residing in the community.
10 articles reviewed Narrative review. The role of informal caregiver is complex and often made more difficult because of increasing medication regimen complexities, aspects of the relationship between the caregiver and the care recipient, health care system practices, and a lack of information and/or training available to the informal caregiver, especially when caring for people living with dementia.
(Continues)   12 To explore the relationship between medication non-adherence and specific cognitive domains in persons with CI, and to discover determinants of medication non-adherence 15 articles were reviewed A systematic review This review found poor cognitive function as a risk factor of medication non-adherence. It also highlighted the importance of caregivers in assisting with medication adherence or interventions to improve medication adherence. Review also suggested that clinicians should be aware of the negative effect global cognitive impairment has on medication adherence and consider screening patients where impairment is indicated.
individual parts/domains because it is now widely acknowledged that interventions developed to manage medicines require a whole systems view.
Our study confirms that medication management comprised a complex range of activities for the person with dementia-carer dyad.
This finding is in line with existing studies that highlighted medication management as a complex extensive concept that requires a combination of management and organization skills, clinical knowledge, and understanding of medicine safety. 31,34,43 Unsurprisingly, our study identified wide-ranging system issues relating to medicines management and some corresponding coping strategies, as experienced by people with dementia and/or family carers. These were categorised into cognitive, medication, social and cultural, and knowledge/educational and communication domains.
Analysis of the meta-data from the studies included in this review identified similarities between people with dementia and family carers in their experiences of difficulties surrounding medicines management.
Whilst these similarities could be attributed to "ageing" [while], other studies suggested the family carers' role as advocates for people with dementia to be a key factor. 23,38,39,48 The complexities of managing medicines increases with the pro- With declining cognitive ability, people with dementia are less likely to use internal memory strategies to aid with medication administration. 23 Studies included in this review 25,27,32,36 found that recall of repetitive tasks such as medication administration could be supported by connecting the activity to environmental cues, a strategy that was mentioned by both people with dementia and their family carers. Dose administration aids, specifically the Webster-pak, are common external memory strategies for older people 52-55 and people with dementia used these more frequently than older people. 27 Whilst there is documented evidence that carers have developed coping strategies to help with the organisation of medication for example in ordering, collecting, and storing of medication, there are still gaps to managing cognitive challenges, eg, communicating with people with dementia or communicating with confused uncooperative care recipient highlighting the need to investigate these in future studies.
There appeared to be no coping strategy for managing medication issues such as knowledge about indication of prescribed medication in this study. It is also interesting to note that none of the studies in this review reported support or coping strategies for people with dementia to self-manage their medicines. However, other supporting strategies are in place such as de-prescribing (withdrawing of medications) which has been undertaken with some success 56,57 and the use of home care agencies to help the person with dementia, mainly with their daily living activities with limited roles in managing medicines. There is also greater recognition and advocacy in involving people with dementia in co-design 58-60 although such approaches focusing on managing     medicines is scarce. This presents a need for further research into this area given that many people with dementia live alone in their own homes.
Despite current knowledge of existing coping strategies, there appears to be little insight or in-depth understanding as to how, whether, and in which circumstances these strategies work for people with dementia and/or family carers and any adjustments they make to manage medicines. For example, there is limited literature reporting how and when people with dementia and/or family carers decide to switch from internal memory strategies to external adaptive strategies and, whether and in which circumstances these strategies are effective in managing medication. Future studies are needed to investigate in-depth the "mechanisms of action" of medication management strategies currently employed by people with dementia and/or family carers using realist approaches 61,62 to inform recommendations for managing medicines safety in people's own homes.
Despite the inclusion of people with dementia in some of the studies reviewed in this study, their perspectives towards medicine use such as medication issues and coping strategies were largely missing from the study results; their "voices" did not seem to be represented compared with those of family carers. This is puzzling and could be due to multiple factors such as the study design and how research was conducted with people with dementia. Several studies report efforts to address the issue of study design by carefully considering inclusive approaches that enables people with dementia, largely those with early stages of dementia, to contribute to research in a meaningful way. 63

| Study limitations
Literature searches were limited to the English language and excluded grey literature. The studies reviewed were also largely exploratory in nature, and few specified any theoretical underpinnings to their study design. The two researchers involved in the analysis were from pharmacy/health system/human factors and bio-cultural and medical anthropology backgrounds which may not represent a wide range of perspectives when interpreting findings from studies. To address this limitation, the findings of the systematic review were also discussed with a group of stakeholders (who formed the project advisory group of the wider study within which this systematic review was conducted) that included people living with dementia, family carers, community pharmacist, general practitioner, charity representative, and academics, and presented at an international dementia conference. 71 Overall, the findings resonated with people's personal experiences and further comments were made regarding the lack of appreciation of the "social" domain in everyday clinical practice. Although individual issues identified in this study were not new, feedback received highlighted the systematic, conceptual, and visual way in which medication management issues/domains were presented and the interconnection between domains to be an important addition to the current body of knowledge.

| CONCLUSION
In this study, we identified and modelled wide-ranging system factors influencing the use of medicines, as expressed by people with dementia and/or family carers. Medicines management is a complex set of activities and although current coping strategies exists to manage medication issues, these were primarily used by family carers and/or the person with dementia-carer dyad. There also appear to be few strategies to support cognitive issues such as communication and understanding indications of prescribed medicines. In-depth understanding of how, whether, and in which circumstances coping strategies work for people with dementia and/or carers were largely missing. Although some studies have included people with dementia in their studies, the real "voices" of people with dementia appeared to be largely missing from the literature. Future studies should (1) investigate in-depth the "mechanisms of action" of coping strategies employed by people with dementia and/or carers and (2) include people with dementia as co-producers of research knowledge (ie, doing research collaboratively as opposed to doing research on people with dementia) to underpin further work on developing interventions to enable safe medicines management by people with dementia and/or the person with dementia-carer dyad in their own homes.

AUTHORS' CONTRIBUTIONS
R.L. made a substantial contribution to the conception and design of the work, the interpretation of data, drafting of the paper, and supervision of the study. T.S. made a substantial contribution to the design of the work, the acquisition and interpretation of data, and drafting of the paper. All authors approved the final version of the paper.

FUNDING
The study was part of a study funded by the Wellcome Trust Seed Award in Humanities and Social Science awarded to R.L. (grant number 108320/Z/15/Z). The funders had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.