Assessing What Matters to People Affected by Alzheimer’s Disease: A Quantitative Analysis

Alzheimer’s disease (AD) pathology is often evident among individuals without overt signs or symptoms of dementia, suggesting that AD is best conceptualized as a continuum across both preclinical and clinical stages [1, 2]. Current evidence suggests that the most commonly used clinical outcome assessments may not capture important aspects of living with AD, regardless of stage, such as impacts on psychological and emotional well-being [3]. Therefore, greater insight into the experiences of individuals at risk for or living with AD and their care partners is critical for informing the development of clinically meaningful treatments at different stages of AD.

The What Matters Most (WMM) series is an ongoing initiative designed to evaluate concepts that are important to people affected by AD in a rapidly evolving treatment landscape. Specifically, this initiative aims to better understand and assess treatment-related needs, symptoms, impacts, and outcomes of individuals at risk for or living with AD and the care partners of individuals living with AD. In phase 1 of WMM, we conducted qualitative research with individuals at risk for or living with mild AD and care partners of individuals with more advanced AD to identify a comprehensive set of 42 AD symptoms, impacts, and treatment-related outcomes that are meaningful to individuals across the AD continuum [4]. In phase 2, reported here, individuals at risk for or living with mild AD and the care partners of individuals with moderate to severe AD assessed the importance of the concepts identified in phase 1 to confirm and provide further support for the robustness of phase 1 findings. Based on the WMM phase 2 findings, a subsequent study was conducted to evaluate the extent to which the concepts that are of greatest importance to people with or at risk for AD and their care partners are reflected in the clinical outcome assessments most commonly used in AD clinical trials (DiBenedetti et al., companion manuscript).

This phase in the WMM series confirmed and quantified the symptoms, impacts, and outcomes of AD that had been identified as important in qualitative research with people at risk for or living with AD and care partners of people with moderate to severe AD. Most of the 42 concepts evaluated in the WMM surveys mattered to patient respondents at risk for or with AD, with more than half rating all 42 items as “very important” or “extremely important.” In contrast, fewer than half of the 42 items were rated as “very important” or “extremely important” by at least half of the care partners of people with moderate to severe AD. All respondent groups consistently rated taking medications correctly, being able to stay safe, and not feeling down or depressed as the most important items. These items represent a wide range of domains that shape both patients’ and care partners’ experiences of AD, reflecting a desire to maintain patients’ health, emotional well-being, and safety. Findings from this phase of the WMM work confirm the strength of the phase 1 qualitative findings [4], with consistent importance ratings in this heterogeneous condition.

While the concepts of greatest importance were consistent across all respondent groups, for most items, average care partner importance ratings were lower than ratings provided by people with or at risk for AD. In particular, whether the care recipient was able to work, was able to engage in planning and organizing activities, remembered names of people they just met, and was able to drive were among the items with the lowest importance rating for care partners and were less important than they were to patient respondents. This finding highlights that care partners and individuals living with AD may prioritize the symptoms and impacts of AD differently, and for different reasons. While patients’ focus on maintaining independence may be driven by a desire not to be a burden to their care partners and family, the same concept may have a different underlying driver for care partners, such as the desire to maintain the patient at home. Assessing these impacts and the underlying source of their importance to patients and to care partners may aid in understanding the clinical meaningfulness of current and emerging treatment options from the perspectives of both the patient and the care partner.

Important WMM survey items included symptoms and impacts across a wide range of domains beyond memory, which aligns with prior research [8‐10]. For instance, a recent study examining the relevance of a conceptual model of symptoms and impacts of AD found that emotional and psychological impacts were among the most relevant concepts for patients with mild to moderate AD [3]. Hartry et al. [3] also found that individuals with AD expressed a desire to maintain their health and safety. Other prior work has shown that individuals with AD value maintaining their independence and daily physical functioning [9, 11‐14], quality of life [11], social engagement and ability to communicate [12, 13], and their identity and personality [13], in addition to alleviating symptoms [14]. Research evaluating patients’ and care partners’ goals for AD treatment has revealed that the domains of functioning, leisure, behavior, and social interaction, in addition to cognition, all represent clinically important therapeutic goals for patients and care partners [10]. Our findings complement this prior work, and further demonstrate that symptoms and impacts meaningful to patients with AD and their care partners extend beyond issues with memory, or indeed clinical definitions of “cognition” or “function.” Assessing the effects of a treatment on a range of symptoms and impacts related to AD, including those more distal from the core cognitive and functional impacts such as emotional well-being, may yield a more comprehensive understanding of the true clinical meaningfulness of the treatment’s effect.

It is also noteworthy that respondents in Groups 1–3—ranging from people with unimpaired cognition and evidence of AD pathology to those with a diagnosis of mild AD—reported consistent concerns and desires for therapeutic outcomes. The similarities among Groups 1–3 captured by the WMM surveys suggest that individuals at risk for AD perceive the avoidance of symptoms and impacts of AD in the same way as do patients with mild cognitive impairment or mild AD. This finding provides support for the inclusion of this presymptomatic population in clinical trials for disease-modifying therapies, given the concordance of their perception of treatment benefit with that held by individuals with more advanced disease.

While this phase of the WMM series was not designed to elicit rankings of the 42 concepts of interest from the respondents, the first-of-its-kind findings and importance ratings provide a foundation to begin to understand the concepts and outcomes that are meaningful to people affected by AD across the continuum of disease. The results provide novel insight into the experiences of individuals at risk for or with AD and their care partners, highlight the complexity of what matters to them, and serve as a platform for continued evidence gathering to inform patient-centered evaluations of the clinical meaningfulness of treatment benefits and outcomes across the AD continuum. A subsequent study in the WMM series has explored how the 42 items align with the concepts in commonly used AD clinical outcome assessment measures, thereby elucidating the ability of existing instruments to capture meaningful concepts across AD severity states [15] (DiBenedetti et al., companion manuscript). Future studies in the WMM series are planned to further contextualize WMM findings, to refine the WMM survey to expand its context of use, and to develop a list of prioritized core outcome assessments informed by WMM findings.

Our study has several limitations. While the overall sample consisted of 274 respondents across the continuum of AD and categorized into three groups of patients and two groups of care partners, the number of respondents in each group was relatively small. Further, some clinical details, such as patient respondents’ and care recipients’ genetic-mutation profile, were not collected in this study. The web-based survey design may have limited participation to respondents with internet access, although we did offer respondents a chance to complete the survey in a clinic if they needed help or did not have internet access. Additionally, most respondents were female and had a greater than high school education, and the geographic diversity of respondents (e.g., urban or rural) was unknown. These factors limit the generalizability of our findings. The analyses did not explore whether patients’ and care partners’ survey responses may have been influenced by certain demographic characteristics and living circumstances, such as whether they were employed or lived alone. The potential influences of these factors on respondents’ importance ratings is unknown and will be an interesting topic for future research. There was a clear ceiling effect with the 5-point scale, which makes comparison between items difficult. The cross-sectional study design precludes an assessment of changes in what matters to patients as their disease progresses. Given the differences between the patient and the care partner groups, and the different perspectives they represent, we cannot conduct formal statistical comparisons to further evaluate similarities and differences in importance ratings among individuals across the AD continuum. Finally, individual patients’ and care partners’ priorities for the treatment of AD may include dimensions not reflected in the WMM items (e.g., physical health or aspects of family relations, such as respect, affection, and understanding). The results reported here represent a systematic elicitation of concepts that were confirmed to be important, on average, across the disease spectrum, not the unique perspectives and lived experiences of people living with or affected by AD.

We developed the 42-item WMM survey to confirm and quantify concepts that matter to individuals at risk for or living with AD and to their care partners across the disease continuum. The WMM items were informed by concepts in the literature and systematically identified from qualitative interviews with people at risk for or with AD and their care partners. We found that nearly all of the 42 items were highly important (mattered) to respondents, ranging from asymptomatic individuals with AD pathology to care partners of people with severe AD. Individuals at risk for or with AD rated more items as important than did care partners, indicating the importance of individual as well as caregiver input. Ratings of importance across the 42 items by individuals who were presymptomatic but with underlying evidence of AD (Group 1) were highly consistent with those rating by individuals with diagnosed cognitive impairment due to AD (Group 2) and with those with mild AD (Group 3). Notably, both patient respondents in Groups 1–3 and care partner respondents in Groups 4 and 5 agreed on the importance of taking medications correctly, not feeling down or depressed, and being able to stay safe. Additionally, a wide range of items, extending beyond cognition and gross functional ability were important to individuals at risk for or with AD and to their care partners, including emotional well-being and a desire to maintain independence, overall physical and mental health, and safety.