In this pan-European study, we identified a core list with outcomes relevant to patients and care partners in the disease trajectory of Alzheimer’s disease (AD). Patients and care partners largely identified similar outcomes as most important, including memory deterioration, loss of legal capacity, no longer recognizing (significant) others, and the patients’ ability to convey what they want to say, take care of their self and live in their own home. Most selected outcomes were from the category ‘cognition’, followed by items in the categories ‘functioning and dependency’ and ‘physical health’.
Many patients perceive the neuropsychological examination as stressful, yet our results show that they highly value a prognosis in terms of cognitive outcomes. Patients and care partners are keen to know about the (expected) course of the cognitive outcomes.17 The current study underlines that we should bridge the gap between cognitive test scores and daily functioning, by making an effort to translate numerical cognitive test results to the cognitive outcomes such as mentioned in this study.
Contrary to our expectation, outcomes from the category ‘behavior and neuropsychiatry’, such as anxiety and apathy, were not often selected by our participants as most important. This finding is in correspondence with results from a previous study, reporting that anxiety and depressive symptoms were not highly prioritized by patients with mild cognitive impairment (MCI) and their care partners.11 Nonetheless, behavioral and psychological symptoms are highly prevalent across the entire spectrum of AD, with 96% of the patients showing at least one symptom.18, 19 Former studies reported that these symptoms were associated with increased risk of institutionalization, difficulties in daily functioning and caregiver burden.20, 21 We could speculate that symptoms from the category ‘behavior and neuropsychiatry’ may be more relevant at a later stage, or that patients and care partners may not have realized that these symptoms are related to AD. Alternatively, these symptoms may not be the most striking aspect of managing AD in everyday life, and this could be different in other types of dementia such as dementia with Lewy bodies or frontotemporal dementia, where behavioral and psychological signs and symptoms are more in the foreground.22, 23
We observed large variability in the importance rating of individual items, as 33 out of the list of 59 were rated as ‘most important’ by at least one patient or caregiver. When scrutinizing the individual items, some showed some overlap with other items from the same category. For example the items ‘How long am I able to recognize my family and friends’ and ‘When do I no longer recognize anyone?’ from the category cognition showed resemblance since they both focused on the ability to recognize others. Nevertheless, on a category level, it was clear that most patients and care partners identified items related to cognitive decline and functional dependence as most important. In view of the large variability in items selected as most important, it was even more remarkable that outcomes deemed relevant by patients and care partners were very similar. Seven out of ten items in both the patient and care partner top10-lists were concordant, justifying us merging these lists into one core outcome list of 13 items. For both patients and care partners, outcomes from the category ‘cognition’ and ‘functioning and dependency’ were identified as most important. However, the differences are also interesting. Care partners for example indicated a strong wish to know the patient’s life expectancy. Patients on the other hand emphasized the importance of maintaining their ability to participate meaningfully in conversations. By merging the top-10 lists of both patients and care partners into one core outcome list, the perspectives of both stakeholder groups are equally well represented.
To our knowledge, this is the first study that has investigated outcomes of relevance to patients and care partners in the disease trajectory of AD (AD dementia, MCI and SCD) in multiple European countries, using a mixed-method approach. A former review reported comparable results in relevant outcomes of patients with MCI or AD and their care partners and health care providers.24 This review identified some outcomes mentioned in our study, e.g. memory, mental health, activities of daily living and maintenance of identity. Outcomes that we did not replicate are eating behaviors, apathy and self-efficacy in the ability to manage memory impairment. In addition, a recent qualitative study examined what matters most to patients and care partners across the AD continuum, by means of interviews only.25 They also observed that memory (e.g. forgetting friends/family) was reported as one of the most challenging issues by the majority of the participants. In addition, they reported that the impacts of AD vary across the disease-severity spectrum. Emotional impacts (e.g. more frustrated) and social impacts (e.g. decreased social activities) were most commonly reported in the early stages of AD. However, care partners of patients with mild to severe AD reported impacts on their own daily responsibilities as most important.
One of the strengths of our study is the two stepped, mixed-methods approach, whereby we first used a qualitative bottom up strategy to generate a comprehensive list of outcomes, and then a quantitative approach to provide a selection of most important outcomes from the perspectives of a large sample of patients and care partners. Also, we included participants from 13 different European countries, which greatly enhances generalizability.
Among the potential limitations is our use of an online survey, which may have led to an underrepresentation of patients with severe cognitive symptoms and computer illiterate patients. On the other hand, one might argue that with diagnosis of AD occurring in an increasingly early stage, the preferences and wishes with respect to prognosis of these groups are most relevant in this context. Another potential limitation is that identifying the most important items in the online survey was challenging for participants. To support participants in identifying what mattered most to them, we used a stepped approach that made it easier for the participants to select the three items they considered most important. In addition, the fact that behavior and neuropsychiatry were not mentioned as relevant outcomes may be partly due to patients and care partners being unaware that these outcomes are possible and quite likely consequences of AD.
Implications for clinical practice and further research
Information on individual disease trajectories can support patients, care partners and health care providers to plan and organize care. We will use the results of the current study to collect patient-reported outcomes (PROs) in the context of the European ADDITION project. Subsequently, we will integrate these PROs into a disease progression model, which could help to provide patients and care partners with personalized information on their expected disease course. A previous study constructed biomarker-based models for prediction of progression to dementia in MCI patients.26 The next step is to predict other outcomes relevant to patients and care partners.
Based on our results, it can be debated whether the data we routinely collect during follow-up at the memory clinic (i.e. medical exam, cognitive testing) sufficiently reflects the outcomes that are most relevant. We should focus more on data collection of PROs, such as identified in the current study. Moreover, previous studies investigated the views of healthcare professionals regarding important outcomes in AD, and reported driving,13 patient and care partner quality of life,13, 27 maintaining personality and identity13 and behavior changes13, 28 as relevant. These did however not end up in our core outcome list from the perspective of patients and care partners. This would suggest that important outcomes from the perspective of healthcare professionals are additionally relevant and could also be taken into account when investigating PROMs in AD-studies. Of note, seven (7.1%) patients and three (2.3%) care partners reported that they did not want to know anything about the progression of the symptoms in our study. Therefore, it is important to adopt a process of shared decision making in memory clinics ,29 in which patients, care partners and clinician decide together on the prognostic information about the course of AD which is most relevant to patients and their care partners.
In addition, to follow patients more efficiently, we could make more use of online opportunities, and this has particularly become relevant in the current times with COVID19 related regulations that hamper physical visits. We will incorporate our core outcome list in a large-scale online data-collection of PROs, supplemented with outcomes that are deemed relevant from the perspective of the professionals (e.g. quality of life and behavior changes). In our online data collection, in addition to questionnaires on quality of life and activities of daily living, we include questions about their social environment, patients’ ability to participate in conversations, to recognize loved ones and to keep up hobbies. Some outcomes identified in our study are too abstract or otherwise impossible to inquiry by means of a questionnaire (e.g. how long am I able to convey what I want to say?). Acknowledging these uncertainties and the impossibility to adequately answer these questions might help them cope.30
This study resulted in a comprehensive core list of 13 outcomes in the AD trajectory relevant to both patients and care partners. These outcomes can be incorporated in patient care, research, for example via online survey. Integration of these outcomes into a disease progression model can help to provide patients and care partners with personalized information on prognosis of AD.